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Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors
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Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors

A special issue of Journal of Cardiovascular Development and Disease (ISSN 2308-3425). This special issue belongs to the section "Basic and Translational Cardiovascular Research".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 46901

Special Issue Editors

Prof. Dr. Gerhard Kostner

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Guest Editor
Institute of Molecular Biology and Biochemistry, Medical University of Graz, Neue Stiftingtalstraße 6/VI, A-8010 Graz, Austria
Interests: lipid and lipoprotein metabolism; lipid oxidation; atherogenesis; transcriptional regulation; micro-RNA; T2DM
Special Issues, Collections and Topics in MDPI journals
Dr. Karam Kostner

E-Mail Website
Guest Editor
MD, PhD, FRACP, FCSANZ Director Cardiology, Mater Hospital Brisbane, Associate Professor Medicine UQ Past President Cardiac Society Australia and NZ, Qld Raymond Terrace, South Brisbane, QLD 4101, Australia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Scientists，

Due to the success of our previous Guest Editor activities, we considered it important to launch a new Special Issue on “Atherosclerosis”. Although much progress has been achieved in recent years, there is no doubt that intensive efforts are necessary to improve treatment of cardiovascular disease, which is still increasing in numerous countries. The reasons for that are manifold and include not only epigenetic phenomena but also the progress of civilization, the vast supply of unhealthy food, the surge of pollution, and the increase in sedentary life-style. It is therefore of eminent importance to bring leading scientists working in this field together to contribute with their expertise to this endeavor. We invite you to submit your high-quality research on all aspects of atherosclerosis, including genetic and epigenetic aspects, primary and secondary dyslipidemias, risk-factor screening, nutrition, and drug treatment. We accept original articles and reviews that highlight new advancements in atherosclerosis.

Prof. Dr. Gerhard Kostner
Prof. Karam Kostner
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Cardiovascular Development and Disease is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • New developments in genetic and epigenetic risk factors
  • Diagnosis of atherosclerosis
  • Treatment with emphasis on new medications
  • Nutrition, nutraceuticals and functional foods
  • Lipoprotein and apo-lipoprotein metabolism
  • Lp(a)
  • Primary and secondary dyslipidemias

Published Papers (16 papers)

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Research

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13 pages, 945 KiB  
Article
The Association of Triglyceride to High-Density Lipoprotein Cholesterol Ratio with High-Risk Coronary Plaque Characteristics Determined by CT Angiography and Its Risk of Coronary Heart Disease
by Yuji Koide, Toru Miyoshi, Takahiro Nishihara, Mitsutaka Nakashima, Keishi Ichikawa, Takashi Miki, Kazuhiro Osawa and Hiroshi Ito
J. Cardiovasc. Dev. Dis. 2022, 9(10), 329; https://doi.org/10.3390/jcdd9100329 - 28 Sep 2022
Cited by 2 | Viewed by 4223
Abstract
The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is an independent risk index for cardiovascular events. This study aimed to evaluate the association between TG/HDL-C ratio and coronary plaque characteristics as seen on coronary computed tomography angiography (CCTA) and the corresponding increase in [...] Read more.
The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is an independent risk index for cardiovascular events. This study aimed to evaluate the association between TG/HDL-C ratio and coronary plaque characteristics as seen on coronary computed tomography angiography (CCTA) and the corresponding increase in the likelihood of cardiovascular events. A total of 935 patients who underwent CCTA for suspected coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined based on three characteristics: positive remodeling, low-density plaques, and spotty calcification. Significant stenosis was defined as luminal narrowing of >70%. Patients with a higher TG/HDL-C ratio showed significantly greater prevalence of HRP and significant stenosis than patients with low TG/HDL-C ratios (p < 0.01). Multivariate logistic analysis demonstrated that the TG/HDL-C ratio was significantly associated with the presence of HRP (p < 0.01) but not with significant coronary stenosis (p = 0.24). During the median follow-up period of 4.1 years, 26 cardiovascular events including cardiovascular death and acute coronary syndrome occurred. The highest TG/HDL-C tertile was associated with cardiovascular events, with the lowest TG/HDL-C tertile as the reference (hazard ratio, 3.75; 95% confidence interval, 1.04–13.50). A high TG/HDL-C ratio is associated with the presence of CCTA-verified HRP, which can lead to cardiovascular events in patients with suspected CAD. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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15 pages, 1256 KiB  
Article
LPA Genotypes and Haplotypes Are Associated with Lipoprotein(a) Levels but Not Arterial Wall Properties in Stable Post-Coronary Event Patients with Very High Lipoprotein(a) Levels
by Andreja Rehberger Likozar, Aleš Blinc, Katarina Trebušak Podkrajšek and Miran Šebeštjen
J. Cardiovasc. Dev. Dis. 2021, 8(12), 181; https://doi.org/10.3390/jcdd8120181 - 13 Dec 2021
Cited by 7 | Viewed by 2285
Abstract
Lipoprotein(a) [Lp(a)] levels are an independent risk factor for coronary artery disease (CAD). Two single-nucleotide polymorphisms (rs10455872, rs3798220) and number of KIV-2 repeats in the gene encoding Lp(a) (LPA) are associated with Lp(a) and CAD. Our aim was to investigate whether [...] Read more.
Lipoprotein(a) [Lp(a)] levels are an independent risk factor for coronary artery disease (CAD). Two single-nucleotide polymorphisms (rs10455872, rs3798220) and number of KIV-2 repeats in the gene encoding Lp(a) (LPA) are associated with Lp(a) and CAD. Our aim was to investigate whether in patients with stable CAD and high Lp(a) levels these genetic variants are associated with increased Lp(a) and arterial wall properties. Blood samples underwent biochemical and genetic analyses. Ultrasound measurements for the functional and morphological properties of arterial wall were performed. Genotypes of rs10455872 and haplotypes AT and GT showed significant association with Lp(a) levels. Patients with GG showed significantly higher Lp(a) levels compared with those with AG genotype (2180 vs. 1391 mg/L, p = 0.045). Patients with no AT haplotype had significantly higher Lp(a) compared to carriers of one AT haplotype (2158 vs. 1478 mg/L, p = 0.023) or two AT haplotypes (2158 vs. 1487 mg/L, p = 0.044). There were no significant associations with the properties of the arterial wall. Lp(a) levels significantly correlated also with number of KIV-2 repeats (r = −0.601; p < 0.0001). In our patients, these two LPA polymorphisms and number of KIV-2 repeats are associated with Lp(a), but not arterial wall properties. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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8 pages, 2538 KiB  
Article
Bone Marrow Ts65Dn Trisomy-Induced Changes in Platelet Functionality and Lymphocytopenia Do Not Impact Atherosclerosis Susceptibility in Mice
by Suzanne J. A. Korporaal, Ronald J. van der Sluis, Miranda Van Eck and Menno Hoekstra
J. Cardiovasc. Dev. Dis. 2021, 8(9), 110; https://doi.org/10.3390/jcdd8090110 - 13 Sep 2021
Viewed by 1797
Abstract
The genetic disorder Down syndrome is associated with a decreased susceptibility for atherosclerotic cardiovascular disease. Hematological and immune abnormalities occur frequently in Down syndrome patients. We evaluated, in a preclinical setting, the impact of a Down syndrome-like hematological/immune phenotype on atherosclerosis susceptibility. Hereto, [...] Read more.
The genetic disorder Down syndrome is associated with a decreased susceptibility for atherosclerotic cardiovascular disease. Hematological and immune abnormalities occur frequently in Down syndrome patients. We evaluated, in a preclinical setting, the impact of a Down syndrome-like hematological/immune phenotype on atherosclerosis susceptibility. Hereto, hypercholesterolemic low-density lipoprotein receptor knockout mice were transplanted with bone marrow from either a trisomic Ts65Dn mouse or euploid wild-type control and subsequently fed a Western-type diet to induce the development of atherosclerotic lesions. T and B cell concentrations were markedly reduced in blood of Ts65Dn bone marrow recipients (p < 0.001). Expression levels of the pro-atherogenic scavenger receptor CD36 were respectively 37% and 59% lower (p < 0.001) in trisomic monocytes and macrophages. However, these combined effects did not translate into an altered atherosclerosis susceptibility. Notably, blood platelet numbers were elevated in Ts65Dn bone marrow recipients (+57%; p < 0.001), which was paralleled by higher platelet GPVI protein expression (+35%; p < 0.001) and an enhanced collagen-induced platelet activation (p < 0.001). In conclusion, we have shown that providing mice with a Down syndrome-like hematological profile does not change the susceptibility to atherosclerosis. Furthermore, our studies have uncovered a novel effect of the trisomy on platelet functionality that may be relevant in human clinical settings. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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14 pages, 1673 KiB  
Article
The Association of Lipoprotein(a) and Circulating Monocyte Subsets with Severe Coronary Atherosclerosis
by Olga I. Afanasieva, Anastasya Yu. Filatova, Tatiana I. Arefieva, Elena A. Klesareva, Alexandra V. Tyurina, Natalia V. Radyukhina, Marat V. Ezhov and Sergei N. Pokrovsky
J. Cardiovasc. Dev. Dis. 2021, 8(6), 63; https://doi.org/10.3390/jcdd8060063 - 01 Jun 2021
Cited by 11 | Viewed by 2757
Abstract
Background and aims: Chronic inflammation associated with the uncontrolled activation of innate and acquired immunity plays a fundamental role in all stages of atherogenesis. Monocytes are a heterogeneous population and each subset contributes differently to the inflammatory process. A high level of lipoprotein(a) [...] Read more.
Background and aims: Chronic inflammation associated with the uncontrolled activation of innate and acquired immunity plays a fundamental role in all stages of atherogenesis. Monocytes are a heterogeneous population and each subset contributes differently to the inflammatory process. A high level of lipoprotein(a) (Lp(a)) is a proven cardiovascular risk factor. The aim of the study was to investigate the association between the increased concentration of Lp(a) and monocyte subpopulations in patients with a different severity of coronary atherosclerosis. Methods: 150 patients (124 males) with a median age of 60 years undergoing a coronary angiography were enrolled. Lipids, Lp(a), autoantibodies, blood cell counts and monocyte subpopulations (classical, intermediate, non-classical) were analyzed. Results: The patients were divided into two groups depending on the Lp(a) concentration: normal Lp(a) < 30 mg/dL (n = 82) and hyperLp(a) ≥ 30 mg/dL (n = 68). Patients of both groups were comparable by risk factors, autoantibody levels and blood cell counts. In patients with hyperlipoproteinemia(a) the content (absolute and relative) of non-classical monocytes was higher (71.0 (56.6; 105.7) vs. 62.2 (45.7; 82.4) 103/mL and 17.7 (13.0; 23.3) vs. 15.1 (11.4; 19.4) %, respectively, p < 0.05). The association of the relative content of non-classical monocytes with the Lp(a) concentration retained a statistical significance when adjusted for gender and age (r = 0.18, p = 0.03). The severity of coronary atherosclerosis was associated with the Lp(a) concentration as well as the relative and absolute (p < 0.05) content of classical monocytes. The high content of non-classical monocytes (OR = 3.5, 95% CI 1.2–10.8) as well as intermediate monocytes (OR = 8.7, 2.5–30.6) in patients with hyperlipoproteinemia(a) were associated with triple-vessel coronary disease compared with patients with a normal Lp(a) level and a low content of monocytes. Conclusion: Hyperlipoproteinemia(a) and a decreased quantity of classical monocytes were associated with the severity of coronary atherosclerosis. The expansion of CD16+ monocytes (intermediate and non-classical) in the presence of hyperlipoproteinemia(a) significantly increased the risk of triple-vessel coronary disease. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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11 pages, 986 KiB  
Article
Obesity Does Not Interfere with the Cholesterol-Lowering Effect of Plant Stanol Ester Consumption (as Part of a Heart-Healthy Diet)
by Piia Simonen, Elisa Arte and Helena Gylling
J. Cardiovasc. Dev. Dis. 2021, 8(4), 36; https://doi.org/10.3390/jcdd8040036 - 07 Apr 2021
Cited by 1 | Viewed by 2422
Abstract
Dietary modifications including plant stanol ester consumption are recommended measures to control serum and low-density lipoprotein (LDL)-cholesterol concentrations, but obesity can affect their responses. We investigated whether body mass index (BMI) affects serum cholesterol levels during plant stanol (mainly sitostanol) ester consumption. This [...] Read more.
Dietary modifications including plant stanol ester consumption are recommended measures to control serum and low-density lipoprotein (LDL)-cholesterol concentrations, but obesity can affect their responses. We investigated whether body mass index (BMI) affects serum cholesterol levels during plant stanol (mainly sitostanol) ester consumption. This ad hoc analysis was based on earlier results of a cross-over, randomized controlled trial of postmenopausal women consuming rapeseed oil-based margarine without or with plant stanol ester (3 g plant stanols/day) for seven weeks. We classified the subjects as normal-weight (BMI ≤ 25 kg/m2, n = 9, mean 22.6 kg/m2) or overweight/obese (BMI > 25 kg/m2, n = 11, mean 28.4 kg/m2), and recalculated the results, focusing on cholesterol absorption, cholesterol synthesis, and fecal steroid outputs. Serum cholesterol levels were similar in the groups during the control diet. Plant stanol ester reduced serum cholesterol by 0.63 ± 0.19 mmol/L (11%) in normal-weight and by 0.75 ± 0.13 mmol/L (12%) in overweight/obese subjects (p < 0.05 for both), and cholesterol absorption was reduced in both groups. However, relative and dietary cholesterol absorption were more effectively reduced in normal-weight subjects. In conclusion, overweight/obesity did not interfere with the serum cholesterol response to plant stanol ester consumption despite substantial differences in cholesterol metabolism between the groups. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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11 pages, 906 KiB  
Article
Lipoprotein(a), Immunity, and Inflammation in Polyvascular Atherosclerotic Disease
by Narek A. Tmoyan, Olga I. Afanasieva, Marat V. Ezhov, Elena A. Klesareva, Tatiana V. Balakhonova and Sergei N. Pokrovsky
J. Cardiovasc. Dev. Dis. 2021, 8(2), 11; https://doi.org/10.3390/jcdd8020011 - 27 Jan 2021
Cited by 11 | Viewed by 3013
Abstract
Background and aims: lipoprotein(a) (Lp(a)) is a genetically determined risk factor for coronary artery disease and its complications, although data on the association with other vascular beds and the severity of atherosclerosis is limited. The aim of this study was to evaluate the [...] Read more.
Background and aims: lipoprotein(a) (Lp(a)) is a genetically determined risk factor for coronary artery disease and its complications, although data on the association with other vascular beds and the severity of atherosclerosis is limited. The aim of this study was to evaluate the association of atherosclerosis of various vascular beds with Lp(a), as well as its autoantibodies and generalized inflammatory markers. Material and methods: this study included 1288 adult patients with clinical and imaging examination of three vascular beds (coronary, carotid, and lower limb arteries). Patients were categorized according to the number of affected vascular beds (with at least one atherosclerotic stenosis ≥50%): 0 (n = 339), 1 (n = 470), 2 (n = 315), 3 (n = 164). We assessed blood cell count, lipid profile, C-reactive protein, circulating immune complexes, Lp(a), and its autoantibodies. Results: the number of affected vascular beds was associated with an increasing level of Lp(a) and a lower level of IgM autoantibodies to Lp(a). Hyperlipoproteinemia(a) (Lp(a) ≥ 30 mg/dL) was detected more frequently in patients with atherosclerosis. In logistic regression analysis adjusted for age, sex, hypertension, type 2 diabetes, and smoking, an elevated Lp(a) level was independently associated with stenotic atherosclerosis and lesion severity. There was a positive association of the number of affected vascular beds with C-reactive protein (r = 0.21, p < 0.01) and a negative association with circulating immune complexes (r = −0.29, p < 0.01). The neutrophil-to-lymphocyte ratio was significantly higher and the lymphocyte-to-monocyte ratio was significantly lower in patients with atherosclerosis compared to the controls (p < 0.01). Conclusion: Lp(a), C-reactive protein, circulating immune complexes, and neutrophil-to-lymphocyte ratio are associated with the stenotic atherosclerosis of different vascular beds. Lp(a) levels increase and IgM autoantibodies to Lp(a) decrease with the number of affected vascular beds. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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12 pages, 704 KiB  
Article
Triglycerides to High-Density Lipoprotein Cholesterol Ratio Predicts Chronic Renal Disease in Patients without Diabetes Mellitus (STELLA Study)
by Vaia D. Raikou, Despina Kyriaki and Sotiris Gavriil
J. Cardiovasc. Dev. Dis. 2020, 7(3), 28; https://doi.org/10.3390/jcdd7030028 - 01 Aug 2020
Cited by 3 | Viewed by 2696
Abstract
Background: The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been included in the potential indices for atherosclerosis in chronic kidney disease (CKD). In this study, we addressed the role of the TG/HDL-C ratio on CKD prediction defined by both classified estimated glomerular [...] Read more.
Background: The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been included in the potential indices for atherosclerosis in chronic kidney disease (CKD). In this study, we addressed the role of the TG/HDL-C ratio on CKD prediction defined by both classified estimated glomerular filtration rate (eGFR) and classified urinary albumin-to-creatinine ratio (UACR) in non-diabetic participants. Methods: One hundred and eighty-three subjects with a mean age 67.3 ± 15.6 years old were included. Our participants were classified in both eGFR and UACR categories according to the Kidney Disease Improving Global Outcomes 2012 criteria. Estimated pulse wave velocity (ePWV) was calculated using an equation from age and mean blood pressure. The TG/HDL-C ratio was calculated. X2 tests and adjusted models were applied using confounders. Results: The TG/HDL-C ratio was inversely associated with eGFR and positively with both UACR and ePWV. We divided our patients in two groups according to the found ROC curve of the TG/HDL-C ratio cut-off point, either with an eGFR of less or more than 60 mL/min/1.73 m2. X2 tests showed significant association between the high TG/HDL-C ratio and classified eGFR, and classified UACR and hypertension (x2 = 24.5, p = 0.001, x2 = 12.5, p = 0.002 and x2 = 12.6, p = 0.001, respectively). The adjusted model showed the high TG/HDL-C ratio to be an independent predictor for both a low eGFR and UACR (OR = 1.5, 1.2–1.9 and OR = 1.22, 1.02–1.47, respectively) in combination with old age and hypertension. Conclusion: The TG/HDL-C ratio was revealed to be a potential predictor for both a low eGFR and micro/macroalbuminuria in non-diabetic patients. The arterial stiffening was included in the main underlying pathophysiological mechanisms. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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9 pages, 1209 KiB  
Article
Why Some Patients Undergoing Lipoprotein Apheresis Therapy Develop New Cardiovascular Events?
by Ulrich Julius, Solveig Kuss, Sergey Tselmin, Ulrike Schatz and Stefan R. Bornstein
J. Cardiovasc. Dev. Dis. 2020, 7(3), 25; https://doi.org/10.3390/jcdd7030025 - 16 Jul 2020
Cited by 6 | Viewed by 2472
Abstract
Lipoprotein apheresis (LA) is an effective tool to reduce cardiovascular events (CVEs) in high-risk patients with elevations of low density lipoprotein-cholesterol (LDL-C) and/or Lipoprotein(a) (Lp(a)). All patients included into this retrospective analysis had experienced CVEs before the start of the LA therapy. We [...] Read more.
Lipoprotein apheresis (LA) is an effective tool to reduce cardiovascular events (CVEs) in high-risk patients with elevations of low density lipoprotein-cholesterol (LDL-C) and/or Lipoprotein(a) (Lp(a)). All patients included into this retrospective analysis had experienced CVEs before the start of the LA therapy. We compared personal and lab data in two groups: CVEx/0 (n 60) with no new events during LA therapy, CVEx/1+ (n 48) with at least one new event. Patients of Group CVEx/1+ were about 5 years older when they had started the extracorporeal therapy, and they experienced more CVEs prior to that timepoint. There was a positive correlation between the number of CVEs before and during LA therapy. No differences were seen with respect to lipid concentrations, even after a correction of LDL-C concentrations for the LDL-C transported with Lp(a) particles. LA sessions effectively reduced both LDL-C and Lp(a). Lp(a) levels measured before LA sessions were lower than those measured initially. It appeared difficult to reach the target values for LDL-C published in the ESC/EAS Guideline in 2019, although all patients were maximally treated including drugs when tolerated. In conclusion, it will be important to initiate an LA therapy earlier, at least after a second CVE and at a younger age. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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Review

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17 pages, 7318 KiB  
Review
The Mechanism and Role of N6-Methyladenosine (m6A) Modification in Atherosclerosis and Atherosclerotic Diseases
by Quandan Tan, Song He, Xinyi Leng, Danni Zheng, Fengkai Mao, Junli Hao, Kejie Chen, Haisong Jiang, Yapeng Lin and Jie Yang
J. Cardiovasc. Dev. Dis. 2022, 9(11), 367; https://doi.org/10.3390/jcdd9110367 - 25 Oct 2022
Cited by 2 | Viewed by 1860
Abstract
N6-methyladenosine (m6A) modification is a newly discovered regulatory mechanism in eukaryotes. As one of the most common epigenetic mechanisms, m6A’s role in the development of atherosclerosis (AS) and atherosclerotic diseases (AD) has also received increasing attention. Herein, [...] Read more.
N6-methyladenosine (m6A) modification is a newly discovered regulatory mechanism in eukaryotes. As one of the most common epigenetic mechanisms, m6A’s role in the development of atherosclerosis (AS) and atherosclerotic diseases (AD) has also received increasing attention. Herein, we elucidate the effect of m6A on major risk factors for AS, including lipid metabolism disorders, hypertension, and hyperglycemia. We also describe how m6A methylation contributes to endothelial cell injury, macrophage response, inflammation, and smooth muscle cell response in AS and AD. Subsequently, we illustrate the m6A-mediated aberrant biological role in the pathogenesis of AS and AD, and analyze the levels of m6A methylation in peripheral blood or local tissues of AS and AD, which helps to further discuss the diagnostic and therapeutic potential of m6A regulation for AS and AD. In summary, studies on m6A methylation provide new insights into the pathophysiologic mechanisms of AS and AD, and m6A methylation could be a novel diagnostic biomarker and therapeutic target for AS and AD. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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44 pages, 1028 KiB  
Review
Genomic Variants and Multilevel Regulation of ABCA1, ABCG1, and SCARB1 Expression in Atherogenesis
by Alexandra V. Rozhkova, Veronika G. Dmitrieva, Elena V. Nosova, Alexander D. Dergunov, Svetlana A. Limborska and Liudmila V. Dergunova
J. Cardiovasc. Dev. Dis. 2021, 8(12), 170; https://doi.org/10.3390/jcdd8120170 - 02 Dec 2021
Cited by 9 | Viewed by 3965
Abstract
Atheroprotective properties of human plasma high-density lipoproteins (HDLs) are determined by their involvement in reverse cholesterol transport (RCT) from the macrophage to the liver. ABCA1, ABCG1, and SR-BI cholesterol transporters are involved in cholesterol efflux from macrophages to lipid-free ApoA-I and [...] Read more.
Atheroprotective properties of human plasma high-density lipoproteins (HDLs) are determined by their involvement in reverse cholesterol transport (RCT) from the macrophage to the liver. ABCA1, ABCG1, and SR-BI cholesterol transporters are involved in cholesterol efflux from macrophages to lipid-free ApoA-I and HDL as a first RCT step. Molecular determinants of RCT efficiency that may possess diagnostic and therapeutic meaning remain largely unknown. This review summarizes the progress in studying the genomic variants of ABCA1, ABCG1, and SCARB1, and the regulation of their function at transcriptional and post-transcriptional levels in atherosclerosis. Defects in the structure and function of ABCA1, ABCG1, and SR-BI are caused by changes in the gene sequence, such as single nucleotide polymorphism or various mutations. In the transcription initiation of transporter genes, in addition to transcription factors, long noncoding RNA (lncRNA), transcription activators, and repressors are also involved. Furthermore, transcription is substantially influenced by the methylation of gene promoter regions. Post-transcriptional regulation involves microRNAs and lncRNAs, including circular RNAs. The potential biomarkers and targets for atheroprotection, based on molecular mechanisms of expression regulation for three transporter genes, are also discussed in this review. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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13 pages, 284 KiB  
Review
Statin Therapy in Post-Operative Atrial Fibrillation: Focus on the Anti-Inflammatory Effects
by Homa Nomani, Amir Hooshang Mohammadpour, Željko Reiner, Tannaz Jamialahmadi and Amirhossein Sahebkar
J. Cardiovasc. Dev. Dis. 2021, 8(3), 24; https://doi.org/10.3390/jcdd8030024 - 26 Feb 2021
Cited by 13 | Viewed by 2679
Abstract
Background: Atrial fibrillation (AF) occurring after cardiac surgery, post-operative AF (POAF), is a serious and common complication of this treatment. POAF may be life-threatening and the available preventive strategies are insufficient or are associated with significantly increased risk of adverse effects, especially in [...] Read more.
Background: Atrial fibrillation (AF) occurring after cardiac surgery, post-operative AF (POAF), is a serious and common complication of this treatment. POAF may be life-threatening and the available preventive strategies are insufficient or are associated with significantly increased risk of adverse effects, especially in long-term use. Therefore, more appropriate treatment strategies are needed. Methods: In this paper, the efficacy, safety, and other aspects of using statins in the prevention of POAF focusing on their anti-inflammatory effects are reviewed. Results: Recent studies have suggested that inflammation has a significant role in POAF, from the first AF episode to its serious complications including stroke and peripheral embolism. On the other hand, statins, the most widely used medications in cardiovascular patients, have pleiotropic effects, including anti-inflammatory properties. Therefore, they may potentially be effective in POAF prevention. Statins, especially atorvastatin, appear to be an effective option for primary prevention of POAF, especially in patients who had coronary artery bypass grafting (CABG), a cardiac surgery treatment associated with inflammation in the heart muscle. However, several large studies, particularly with rosuvastatin, did not confirm the beneficial effect of statins on POAF. One large clinical trial reported higher risk of acute kidney injury (AKI) following high-dose rosuvastatin in Chinese population. In this study, rosuvastatin reduced the level of C-reactive protein (CRP) but did not reduce the rate of POAF. Conclusion: Further studies are required to find the most effective statin regimen for POAF prevention with the least safety concern and the highest health benefits. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
17 pages, 762 KiB  
Review
Role of Selected miRNAs as Diagnostic and Prognostic Biomarkers in Cardiovascular Diseases, Including Coronary Artery Disease, Myocardial Infarction and Atherosclerosis
by Rashid Mir, Imadeldin Elfaki, Naina Khullar, Ajaz Ahmad Waza, Chandan Jha, Mohammad Muzaffar Mir, Shamsu Nisa, Babar Mohammad, Tahir Ahmad Mir, Mohsin Maqbool, Jameel Barnawi, Salem Owaid Albalawi and Faisel M. Abu-Duhier
J. Cardiovasc. Dev. Dis. 2021, 8(2), 22; https://doi.org/10.3390/jcdd8020022 - 19 Feb 2021
Cited by 19 | Viewed by 4712
Abstract
Cardiovascular diseases are the leading cause of death worldwide in different cohorts. It is well known that miRNAs have a crucial role in regulating the development of cardiovascular physiology, thus impacting the pathophysiology of heart diseases. MiRNAs also have been reported to be [...] Read more.
Cardiovascular diseases are the leading cause of death worldwide in different cohorts. It is well known that miRNAs have a crucial role in regulating the development of cardiovascular physiology, thus impacting the pathophysiology of heart diseases. MiRNAs also have been reported to be associated with cardiac reactions, leading to myocardial infarction (MCI) and ultimately heart failure (HF). To prevent these heart diseases, proper and timely diagnosis of cardiac dysfunction is pivotal. Though there are many symptoms associated with an irregular heart condition and though there are some biomarkers available that may indicate heart disease, authentic, specific and sensitive markers are the need of the hour. In recent times, miRNAs have proven to be promising candidates in this regard. They are potent biomarkers as they can be easily detected in body fluids (blood, urine, etc.) due to their remarkable stability and presence in apoptotic bodies and exosomes. Existing studies suggest the role of miRNAs as valuable biomarkers. A single biomarker may be insufficient to diagnose coronary artery disease (CAD) or acute myocardial infarction (AMI); thus, a combination of different miRNAs may prove fruitful. Therefore, this review aims to highlight the role of circulating miRNA as diagnostic and prognostic biomarkers in cardiovascular diseases such as coronary artery disease (CAD), myocardial infarction (MI) and atherosclerosis. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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20 pages, 720 KiB  
Review
The Importance of Telomere Shortening for Atherosclerosis and Mortality
by Wolfgang Herrmann and Markus Herrmann
J. Cardiovasc. Dev. Dis. 2020, 7(3), 29; https://doi.org/10.3390/jcdd7030029 - 06 Aug 2020
Cited by 20 | Viewed by 4149
Abstract
Telomeres are the protective end caps of chromosomes and shorten with every cell division. Short telomeres are associated with older age and adverse lifestyle factors. Leucocyte telomere length (LTL) has been proposed as a biomarker of biological age. The shortening of LTL with [...] Read more.
Telomeres are the protective end caps of chromosomes and shorten with every cell division. Short telomeres are associated with older age and adverse lifestyle factors. Leucocyte telomere length (LTL) has been proposed as a biomarker of biological age. The shortening of LTL with age is the result of the end-replication problem, environmental, and lifestyle-related factors. Epidemiologic studies have shown that LTL predicts cardiovascular disease, all-cause mortality, and death from vascular causes. Age appears to be an important co-variate that explains a substantial fraction of this effect. Although it has been proposed that short telomeres promote atherosclerosis and impair the repair of vascular lesions, existing results are inconsistent. Oxidative stress and chronic inflammation can both accelerate telomere shortening. Multiple factors, including homocysteine (HCY), vitamin B6, and vitamin B12 modulate oxidative stress and inflammation through direct and indirect mechanisms. This review provides a compact overview of telomere physiology and the utility of LTL measurements in atherosclerosis and cardiovascular disease. In addition, it summarizes existing knowledge regarding the impact of oxidative stress, inflammation, HCY, and B-vitamins on telomere function. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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12 pages, 899 KiB  
Systematic Review
Association between Genetic Variants of CELSR2-PSRC1-SORT1 and Cardiovascular Diseases: A Systematic Review and Meta-Analysis
by Rosa Giannina Castillo-Avila, Thelma Beatriz González-Castro, Carlos Alfonso Tovilla-Zárate, José Jaime Martínez-Magaña, María Lilia López-Narváez, Isela Esther Juárez-Rojop, Pedro Iván Arias-Vázquez, Verónica Marusa Borgonio-Cuadra, Nonanzit Pérez-Hernández and José Manuel Rodríguez-Pérez
J. Cardiovasc. Dev. Dis. 2023, 10(3), 91; https://doi.org/10.3390/jcdd10030091 - 21 Feb 2023
Cited by 1 | Viewed by 1593
Abstract
A cluster of three genes CELSR2, PSRC1, and SORT1 has been associated with cardiovascular diseases. Thus, the aim of this study was (i) to perform a systematic review and updated meta-analysis of the association of three polymorphisms (rs646776, rs599839, and rs464218) [...] Read more.
A cluster of three genes CELSR2, PSRC1, and SORT1 has been associated with cardiovascular diseases. Thus, the aim of this study was (i) to perform a systematic review and updated meta-analysis of the association of three polymorphisms (rs646776, rs599839, and rs464218) of this cluster with cardiovascular diseases, and (ii) to explore by PheWAS signals of the three SNPs in cardiovascular diseases and to evaluate the effect of rs599839 with tissue expression by in silico tools. Three electronic databases were searched to identify eligible studies. The meta-analysis showed that the rs599839 (allelic OR 1.19, 95% CI 1.13–1.26, dominant OR 1.22, 95% CI 1.06–1.39, recessive OR 1.23, 95% CI 1.15–1.32), rs646776 (allelic OR 1.46, 95% CI 1.17–1.82) polymorphisms showed an increased risk for cardiovascular diseases. PheWas analysis showed associations with coronary artery disease and total cholesterol. Our results suggest a possible involvement of the CELSR2-PSRC1-SORT1 cluster variants in the risk association of cardiovascular diseases, particularly coronary artery disease. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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8 pages, 2296 KiB  
Systematic Review
Metabolic Syndrome and Its Components in Patients with COVID-19: Severe Acute Respiratory Syndrome (SARS) and Mortality. A Systematic Review and Meta-Analysis
by Sergio Rico-Martín, Julián F. Calderón-García, Belinda Basilio-Fernández, María Zoraida Clavijo-Chamorro and Juan F. Sánchez Muñoz-Torrero
J. Cardiovasc. Dev. Dis. 2021, 8(12), 162; https://doi.org/10.3390/jcdd8120162 - 25 Nov 2021
Cited by 9 | Viewed by 2587
Abstract
Recent meta-analysis studies have reported that metabolic comorbidities such as diabetes, obesity, dyslipidaemia and hypertension are associated with higher risk of severe acute respiratory syndrome (SARS) and mortality in patients with COVID-19. This meta-analysis aims to investigate the relationship between metabolic syndrome (MetS) [...] Read more.
Recent meta-analysis studies have reported that metabolic comorbidities such as diabetes, obesity, dyslipidaemia and hypertension are associated with higher risk of severe acute respiratory syndrome (SARS) and mortality in patients with COVID-19. This meta-analysis aims to investigate the relationship between metabolic syndrome (MetS) and its components with SARS and mortality in COVID-19 patients. Methods: A systematic search was conducted in the several databases up until 1 September 2021. Primary observational longitudinal studies published in peer review journals were selected. Two independent reviewers performed title and abstract screening, extracted data and assessed the risk of bias using the Newcastle–Ottawa Scale. Results: The random effects meta-analysis showed that MetS was significantly associated with SARS with a pooled OR (95% CI) of 3.21 (2.88–3.58) and mortality with a pooled OR (95% CI) of 2.32 (1.16–4.63). According to SARS, the pooled OR for MetS was 2.19 (1.71–2.67), p < 0.001; significantly higher than the hypertension component. With regard to mortality, although the pooled OR for MetS was greater than for its individual components, no significant differences were observed. Conclusions: this meta-analysis of cohort studies, showed that MetS is better associated to SARS and mortality in COVID-19 patients than its individual components. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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7 pages, 1635 KiB  
Case Report
Antiphospholipid Syndrome-Induced Leriche Syndrome in a Man with Lower Limbs Sensory and Motor Defect
by Jeng-Luen Hong, Yueh-Tseng Hou, Po-Chen Lin, Yu-Long Chen, Da-Sen Chien, Giou-Teng Yiang and Meng-Yu Wu
J. Cardiovasc. Dev. Dis. 2021, 8(9), 104; https://doi.org/10.3390/jcdd8090104 - 29 Aug 2021
Cited by 1 | Viewed by 2037
Abstract
Antiphospholipid syndrome (APS) is an autoimmune disorder with characteristics of arterial and/or venous thrombosis due to hypercoagulation status. Although deep vein thrombosis is common, the involvement of arterial thrombosis is more dangerous and poses a high risk of complications. Acute aorto-iliac occlusive disease [...] Read more.
Antiphospholipid syndrome (APS) is an autoimmune disorder with characteristics of arterial and/or venous thrombosis due to hypercoagulation status. Although deep vein thrombosis is common, the involvement of arterial thrombosis is more dangerous and poses a high risk of complications. Acute aorto-iliac occlusive disease (AIOD, known as Leriche syndrome) is severe arterial thrombosis that is associated with high morbidity and mortality rates. Severe acute occlusion may cause spinal cord ischemia, leading to neurological defects, such as acute onset of paraplegia. Co-occurrence of acute aorto-iliac occlusive disease and antiphospholipid syndrome is rare and may present with atypical symptoms mimicking other diseases, including chronic ulcers, musculoskeletal events, and pulmonary diseases. In patients with weak femoral pulses and recurrent thrombotic events, co-occurrence of APS and AIOD should be taken into consideration. Here, we describe a rare case of co-occurrence of APS and AIOD presenting with acute lower leg weakness and numbness. Timely thrombectomies and bilateral common iliac artery stentings rescued distal blood flow. We highlight the clinical features and early diagnosis of co-occurrence of APS and AIOD in order to prevent catastrophic complications. The detailed mechanism and pathogenesis of antiphospholipid syndrome-induced acute aorto-iliac occlusive disease are also discussed. Full article
(This article belongs to the Special Issue Atherosclerosis: Current Concepts of Genetic, Epigenetic and Environmental Risk Factors)
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