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Keywords = coronary artery diseases

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19 pages, 1568 KB  
Article
Long-Term Outcomes in Aortic Stenosis: Mortality Analysis in a Selected Patient Group
by Olga Irtyuga, Mary Babakekhyan, Oleg Metsker, Anna Starshinova, Dmitry Kudlay and Georgy Kopanitsa
J. Pers. Med. 2025, 15(9), 410; https://doi.org/10.3390/jpm15090410 (registering DOI) - 2 Sep 2025
Abstract
Background: Aortic stenosis (AS) is a prevalent acquired heart valve disease with increasing incidence, particularly among older adults. Gender-specific differences in AS presentation, comorbidities, and outcomes remain underexplored, necessitating further investigation to optimize personalized treatment strategies. Objective: To evaluate the clinical and demographic [...] Read more.
Background: Aortic stenosis (AS) is a prevalent acquired heart valve disease with increasing incidence, particularly among older adults. Gender-specific differences in AS presentation, comorbidities, and outcomes remain underexplored, necessitating further investigation to optimize personalized treatment strategies. Objective: To evaluate the clinical and demographic characteristics, comorbidities, and survival outcomes of patients with AS, stratified by gender and aortic valve morphology. Methods: A retrospective analysis of 145,454 echocardiographic examinations (2009–2018) at the Federal State Budgetary Institution “V.A. Almazov National Medical Research Centre” identified 84,851 patients meeting the inclusion criteria (Vmax ≥ 2.0 m/s, age ≥ 18 years). Patients were stratified by gender and valve morphology (bicuspid aortic valve [BAV] vs. tricuspid aortic valve [TAV]). Survival was assessed in 475 pts with AS over a 16-year period (2009–2025) using Kaplan–Meier analysis. Statistical comparisons utilized STATISTICA v. 10.0, with p-values derived from P-tests. Results: Of the cohort, 4998 men and 6322 women had AS. Men with AS were older (median 64 vs. 57 years, p < 0.0001) and had higher systolic blood pressure (140 vs. 130 mmHg, p < 0.0001) than men without AS. Women with AS were also older (median 70 vs. 58 years, p < 0.0001) with higher systolic (140 vs. 130 mmHg, p < 0.0001) and diastolic blood pressure (80 vs. 80 mmHg, p < 0.0001). Men with AS had higher rates of hyperlipidemia (HLP) (26.3% vs. 10.3%, p < 0.0001), while women with AS had increased coronary artery disease (CAD) (35.7% vs. 26.4%, p < 0.0001), diabetes mellitus (DM) (13.4% vs. 10.2%, p < 0.0001), and obesity (10.9% vs. 10.2%, p = 0.06). Chronic heart failure (CHF) was more frequently reported in patients with AS, regardless of gender, compared to patients without AS (in men 53.4% vs. 41.8%, p < 0.0001; in women 54.5% vs. 37.5%, p < 0.0001). BAV was associated with higher AS prevalence (54.5% in men, 66.4% in women). Survival analysis revealed higher mortality. Over the 16-year follow-up period, the mortality rate was 21.7%. Conclusions: Mortality in a representative AS cohort reached 21.7%, underscoring the progressive nature of the disease and its long-term impact. Survival was negatively affected by age over 68.5 years, as well as the presence of aortic regurgitation (AR), increased peak aortic jet velocity, and enlarged maximum aortic diameter. Aortic valve replacement demonstrates an insignificant effect on patient survival rates. Beta-blocker therapy in patients with varying degrees of aortic AS severity has not only demonstrated its safety but has also shown a positive effect on reducing mortality (improving survival). In contrast, the combination of angiotensin II receptor blockers (ARBs) with calcium channel blockers (CCBs) is quite dangerous for patients with AS and reduces their survival. Aortic valve replacement demonstrates an insignificant effect on patient survival rates. In contrast, the absence of fibrinolytic therapy and anticoagulant treatment is associated with an improved prognosis. Conversely, the administration of antiarrhythmic agents and statins is correlated with enhanced survival outcomes, potentially attributable to their influence on coexisting comorbidities. Further research is required to delineate their precise mechanisms and contributions. These results emphasize the importance of early identification, comprehensive risk assessment, and individualized management strategies in improving outcomes for patients with AS. Full article
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62 pages, 4831 KB  
Review
Biodegradable Metal-Based Stents: Advances, Challenges, and Prospects
by Lifeng Sun, Yuanyuan Zeng, Zhengyu Shen, Chongsheng Yue, Yahan Yang, Jia Gao, Junhao Zhang, Qi Yuan and Limei Cha
J. Funct. Biomater. 2025, 16(9), 315; https://doi.org/10.3390/jfb16090315 - 29 Aug 2025
Viewed by 92
Abstract
Cardiovascular disease is a leading cause of global mortality. Percutaneous coronary intervention, which involves the placement of stents to restore blood flow in narrowed arteries, is a widely used treatment. However, traditional stents, such as bare metal stents and drug-eluting stents, can lead [...] Read more.
Cardiovascular disease is a leading cause of global mortality. Percutaneous coronary intervention, which involves the placement of stents to restore blood flow in narrowed arteries, is a widely used treatment. However, traditional stents, such as bare metal stents and drug-eluting stents, can lead to long-term complications such as restenosis, inflammation, and thrombosis. Biodegradable metallic vascular stents, with their superior mechanical properties, excellent biocompatibility, and gradual degradation in vivo, hold significant potential for the treatment of coronary artery disease. This review provides a comprehensive overview of the current research status and challenges. Firstly, it outlines the design principles and performance evaluation methods for biodegradable stents, which focus on mechanical properties, chemical characteristics, corrosion behavior, and biocompatibility. Furthermore, it summarizes the material features, degradation mechanisms, and metabolic behavior of three primary biodegradable metals—magnesium alloys, iron alloys, and zinc alloys—and discusses critical issues such as the degradation rate of different alloys and the development of zinc alloys. Finally, based on the current achievements and challenges of studies on biodegradable metal-based stents, this article proposes some optimization strategies and research prospects. Full article
(This article belongs to the Section Synthesis of Biomaterials via Advanced Technologies)
11 pages, 2792 KB  
Article
Rethinking Access in BEVAR: Single-Center Experience of the Feasibility of Upward-Facing Branches
by Philipp Franke, Imam Tongku Padesma Ritonga, Bachar Al Haj, Yousef Shehada, Martin Austermann and Marco Virgilio Usai
J. Clin. Med. 2025, 14(17), 6106; https://doi.org/10.3390/jcm14176106 - 29 Aug 2025
Viewed by 168
Abstract
This is a single-center study about upward facing in branched endovascular aortic repair. Background: The evolution of branched endovascular aortic repair (BEVAR) has introduced upward-facing branches as a novel approach to facilitate exclusive transfemoral access in complex aortic aneurysm repair. This study [...] Read more.
This is a single-center study about upward facing in branched endovascular aortic repair. Background: The evolution of branched endovascular aortic repair (BEVAR) has introduced upward-facing branches as a novel approach to facilitate exclusive transfemoral access in complex aortic aneurysm repair. This study evaluates the feasibility, safety, and early outcomes of custom-made BEVAR devices incorporating upward-facing branches in patients with cranially oriented renal arteries. The investigation further aims to analyze the technical success and mid-term outcomes related to these novel devices, as well as to identify any challenges or complications specific to the use of upward-facing branches in clinical practice. Methods: We retrospectively analyzed 17 patients treated at a single center between January 2020 and December 2024 using custom-made Cook Medical branched stent grafts with at least one upward-facing branch. Demographics, comorbidities, target vessel details, bridging stent graft (BSG) configurations, and procedure-related complications were collected. The primary endpoints were technical success and branch patency. Secondary endpoints included short- and mid-term branch-related complications. Results: The cohort had a mean age of 70 years, with hypertension (88%) and coronary artery disease (47%) being common comorbidities. Technical success was achieved in 100% of cases. The left renal artery was the most frequently targeted vessel (63.2%). Most upward-facing branches were bridged using a combination of balloon-expandable and self-expandable stents. One patient (5.9%) experienced a renal bleeding complication requiring embolization. There were no cases of primary stent occlusion or dislocation. At a mean follow-up of 14 months, one asymptomatic occlusion of an upward-facing branch was detected in computed tomography angiography. No further upward-facing branch-related complications occurred, and 1-year follow-up was available in 41.2% of patients. Conclusions: In our single-center study including 17 patients, upward-facing branches in BEVAR demonstrate high technical success and a low complication rate, offering a promising alternative to traditional access strategies. These findings support broader adoption in select anatomical scenarios, pending larger comparative studies and longer-term data collection. Full article
(This article belongs to the Special Issue Endovascular Surgery: State of the Art and Clinical Perspectives)
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25 pages, 754 KB  
Review
The Impact of PCSK9 on Diabetic Cardiomyopathy: Mechanisms and Implications
by Haixia Wang, Pei Wang, Yubo Wang, Shuzhen Du, Jing Zhao and Zheng Zhang
Biomolecules 2025, 15(9), 1240; https://doi.org/10.3390/biom15091240 - 27 Aug 2025
Viewed by 248
Abstract
Diabetic cardiomyopathy (DCM) is a common and clinically relevant complication of diabetes mellitus, defined by myocardial dysfunction in the absence of overt coronary artery disease or systemic hypertension. Recent studies have identified proprotein convertase subtilisin/kexin type 9 (PCSK9) as a pivotal mediator in [...] Read more.
Diabetic cardiomyopathy (DCM) is a common and clinically relevant complication of diabetes mellitus, defined by myocardial dysfunction in the absence of overt coronary artery disease or systemic hypertension. Recent studies have identified proprotein convertase subtilisin/kexin type 9 (PCSK9) as a pivotal mediator in the pathogenesis of DCM. PCSK9 contributes not only to dyslipidemia via degradation of LDLR and consequent elevation of circulating LDL-C, but also to metabolic derangements and inflammation through interactions with receptors such as CD36 and Toll-like receptor 4 (TLR4). In DCM, PCSK9 has been shown to exacerbate inflammation and pyroptosis and is closely linked to impaired autophagic function. Elevated circulating PCSK9 has emerged as a potential biomarker for cardiovascular events in patients with type 2 diabetes mellitus (T2DM). At the same time, long-term administration of PCSK9 inhibitors (PCSK9i) has not been associated with a significant increase in incident diabetes. Furthermore, PCSK9 loss-of-function mutations have been linked to a modestly heightened risk of T2DM, underscoring its complex involvement in cardiometabolic regulation and disease. This review synthesizes current insights into the mechanistic and therapeutic roles of PCSK9 in DCM, aiming to inform precision cardiovascular risk management strategies in T2DM populations. Full article
(This article belongs to the Special Issue Cardiometabolic Disease: Molecular Basis and Therapeutic Approaches)
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17 pages, 874 KB  
Review
Coronary Microvascular Dysfunction: Bridging the Diagnosis–Treatment Divide in Women with INOCA—A Review
by Alaukika Agarwal, Ronak Patel and Omar K. Khalique
J. Clin. Med. 2025, 14(17), 6054; https://doi.org/10.3390/jcm14176054 - 27 Aug 2025
Viewed by 385
Abstract
Coronary microvascular dysfunction (CMD) is increasingly being recognized as a significant contributor of ischemic heart disease, particularly affecting women with angina and non-obstructive coronary arteries. This contemporary review synthesizes recent landmark evidence (2022–2024) revealing a striking paradox in CMD management. While diagnostic capabilities [...] Read more.
Coronary microvascular dysfunction (CMD) is increasingly being recognized as a significant contributor of ischemic heart disease, particularly affecting women with angina and non-obstructive coronary arteries. This contemporary review synthesizes recent landmark evidence (2022–2024) revealing a striking paradox in CMD management. While diagnostic capabilities have advanced dramatically—with CMD now identified in 41% of patients with non-obstructive coronary disease—this diagnostic success has not translated into therapeutic benefits. Recent meta-analyses demonstrate that CMD doubles cardiovascular risk (HR 2.08–2.45), yet the first randomized trial of invasive endotyping (CorCTA) found that improved diagnosis failed to improve symptoms despite a 4-fold enhancement in diagnostic accuracy. This diagnosis–treatment gap represents one of the most pressing challenges in contemporary cardiovascular medicine, reflecting fundamental failures that demand urgent reconceptualization. We examine current evidence on its prevalence, diagnostic approaches, and prognostic implications, highlighting the urgent need for CMD-specific therapies to bridge the gap between diagnostic capability and clinical outcomes. Until CMD-specific therapies emerge from dedicated research programs, clinicians must optimize available treatments while advocating for the resources and research focus this condition deserves. Full article
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11 pages, 1500 KB  
Article
Photon-Counting CT Enhances Diagnostic Accuracy in Stable Coronary Artery Disease: A Comparative Study with Conventional CT
by Mitsutaka Nakashima, Toru Miyoshi, Shohei Hara, Ryosuke Miyagi, Takahiro Nishihara, Takashi Miki, Kazuhiro Osawa and Shinsuke Yuasa
J. Clin. Med. 2025, 14(17), 6049; https://doi.org/10.3390/jcm14176049 - 26 Aug 2025
Viewed by 338
Abstract
Background/Objectives: Coronary CT angiography (CCTA) is a cornerstone in evaluating stable coronary artery disease (CAD), but conventional energy-integrating detector CT (EID-CT) has limitations, including calcium blooming and limited spatial resolution. Photon-counting detector CT (PCD-CT) may overcome these drawbacks through enhanced spatial resolution and [...] Read more.
Background/Objectives: Coronary CT angiography (CCTA) is a cornerstone in evaluating stable coronary artery disease (CAD), but conventional energy-integrating detector CT (EID-CT) has limitations, including calcium blooming and limited spatial resolution. Photon-counting detector CT (PCD-CT) may overcome these drawbacks through enhanced spatial resolution and improved tissue characterization. Methods: In this retrospective, propensity score–matched study, we compared CCTA findings from 820 patients (410 per group) who underwent either EID-CT or PCD-CT for suspected stable CAD. Primary outcomes included stenosis severity, high-risk plaque features, and downstream invasive coronary angiography (ICA) referral and yield. Results: The matched cohorts were balanced in demographics and cardiovascular risk factors (mean age 67 years, 63% male). PCD-CT showed a favorable shift in stenosis severity distribution (p = 0.03). High-risk plaques were detected less frequently with PCD-CT (22.7% vs. 30.5%, p = 0.01). Median coronary calcium scores did not differ (p = 0.60). Among patients referred for ICA, those initially evaluated with PCD-CT were more likely to undergo revascularization (62.5% vs. 44.1%), and fewer underwent potentially unnecessary ICA without revascularization (3.7% vs. 8.0%, p = 0.001). The specificity in diagnosing significant stenosis requiring revascularization was 0.74 with EID-CT and 0.81 with PCD-CT (p = 0.04). Conclusions: PCD-CT improved diagnostic specificity for CAD, reducing unnecessary ICA referrals while maintaining detection of clinically significant disease. This advanced CT technology holds promise for more accurate, efficient, and patient-centered CAD evaluation. Full article
(This article belongs to the Section Cardiovascular Medicine)
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18 pages, 2215 KB  
Article
Gut Dysbiosis and Plasma Trimethylamine Oxide Are Associated with Subclinical Coronary Atherosclerosis in Obese Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease
by Kittiya Islam, Pattida Kongsomboonchoke, Maneerat Chayanupatkul, Monravee Tumkosit, Pairoj Chattranukulchai, Pinidphon Prombutara and Pisit Tangkijvanich
Nutrients 2025, 17(17), 2759; https://doi.org/10.3390/nu17172759 - 26 Aug 2025
Viewed by 382
Abstract
Background/Objectives: Gut microbiota has been implicated in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular disease (CVD). This study aimed to identify associations between gut dysbiosis and MASLD, regarding body mass index (BMI) and subclinical coronary atherosclerosis (SCA). Methods [...] Read more.
Background/Objectives: Gut microbiota has been implicated in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular disease (CVD). This study aimed to identify associations between gut dysbiosis and MASLD, regarding body mass index (BMI) and subclinical coronary atherosclerosis (SCA). Methods: We conducted a cross-sectional study of 202 patients with MASLD who had no previous history of CVD. The severity of MASLD was evaluated using a magnetic resonance imaging-based method, and SCA was measured by assessing coronary artery calcification (CAC). Gut microbiota was assessed in fecal specimens using sequencing targeting the V4 region of the 16S rRNA gene. Results: Our results demonstrated that gut microbial profiles between low- and high-BMI groups (<30 vs. ≥30 kg/m2) differed significantly in beta-diversity, but not in alpha-diversity indices. At the genus level, we identified Megamonas, Sutterella, Catenibacterium, and Odoribacter, enriched in the high BMI group. Compared to the low CAC group (<100 AU), MASLD patients with high CAC scores (≥100 AU) exhibited enrichment in Ruminococcus gnavus, Bacteroides, and Lachnoclostridium, along with depletion of several short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibacterium. Multivariate analysis demonstrated that older age, the presence of diabetes, high BMI, fibrosis stage F3-F4, and high plasma trimethylamine oxide (TMAO) levels were independently associated with a high CAC score in patients with MASLD. Conclusions: These data indicated that gut dysbiosis and related metabolites, in association with advanced liver disease, were potential contributors to the progression of SCA in obese patients with MASLD. Full article
(This article belongs to the Section Prebiotics and Probiotics)
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18 pages, 1181 KB  
Article
Reactive Oxygen and Nitrogen Species in Myocardial Infarction: Mechanistic Insights and Clinical Correlations
by Hussein M. Ismail, Sameh A. Ahmed, Ahmed M. Alsaedi, Waleed H. Almaramhy, Man K. Alraddadi, Muhannad S. Albadrani, Ibraheam M. Alhejaily, Faisal A. Mohammad, Anas M. Ghaith and Ali A. Youssef
Med. Sci. 2025, 13(3), 152; https://doi.org/10.3390/medsci13030152 - 24 Aug 2025
Viewed by 287
Abstract
Background/Objectives: Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, driven largely by underlying coronary artery disease (CAD). Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play pivotal mechanistic roles in endothelial dysfunction, atherosclerotic plaque progression, and subsequent cardiac [...] Read more.
Background/Objectives: Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, driven largely by underlying coronary artery disease (CAD). Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play pivotal mechanistic roles in endothelial dysfunction, atherosclerotic plaque progression, and subsequent cardiac injury. Excessive production of these reactive species disrupts cellular redox balance, promotes mitochondrial dysfunction, and accelerates vascular inflammation, ultimately contributing to plaque rupture and MI. This study aimed to investigate the mechanistic associations and clinical correlations of individual ROS and RNS markers in patients with MI. Methods: We conducted a case–control study including 86 patients with MI and 60 age- and sex-matched controls without cardiovascular disease, recruited from the Medina Cardiac Center in Saudi Arabia. The MI cohort was subdivided into ST-elevation MI (STEMI, n = 62) and non-ST-elevation MI (NSTEMI, n = 24) to explore potential differences in oxidative and nitrosative stress profiles. Serum levels of multiple ROS (including hydrogen peroxide, hydroxyl radical, and superoxide anion) and RNS (including nitric oxide and peroxynitrite) were quantified using validated fluorescence-based assays. Clinical and biochemical parameters, including lipid profiles, troponin, and left ventricular ejection fraction, were also assessed. Results: Most ROS and RNS markers were significantly elevated in MI patients compared to controls (p < 0.05), except for nitrogen dioxide. Moderate to strong positive correlations were observed between ROS/RNS levels and serum total cholesterol and LDL-cholesterol (p < 0.001). In contrast, weak or non-significant correlations were found between ROS/RNS markers and serum troponin or left ventricular ejection fraction. Both STEMI and NSTEMI subgroups demonstrated significantly higher oxidative and nitrosative stress levels compared to controls, with distinct patterns between the subtypes. Conclusions: This study underscores a mechanistic link between elevated ROS/RNS levels and myocardial infarction, supporting the importance of targeting oxidative and nitrosative pathways as potential therapeutic strategies. Full article
(This article belongs to the Section Cardiovascular Disease)
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27 pages, 3086 KB  
Article
Trimetazidine–Profen Hybrid Molecules: Synthesis, Chemical Characterization, and Biological Evaluation of Their Racemates
by Diyana Dimitrova, Stanimir Manolov, Iliyan Ivanov, Dimitar Bojilov, Nikol Dimova, Gabriel Marc, Smaranda Oniga and Ovidiu Oniga
Pharmaceuticals 2025, 18(9), 1251; https://doi.org/10.3390/ph18091251 - 23 Aug 2025
Viewed by 408
Abstract
Background: Trimetazidine is a clinically established cardioprotective agent with anti-ischemic and antioxidant properties, widely used in the management of coronary artery disease. Combining its metabolic and cytoprotective effects with the potent anti-inflammatory activity of profens presents a promising therapeutic strategy. Methods: Five novel [...] Read more.
Background: Trimetazidine is a clinically established cardioprotective agent with anti-ischemic and antioxidant properties, widely used in the management of coronary artery disease. Combining its metabolic and cytoprotective effects with the potent anti-inflammatory activity of profens presents a promising therapeutic strategy. Methods: Five novel trimetazidine–profen hybrid compounds were synthesized using N,N′-dicyclohexylcarbodiimide-mediated coupling and structurally characterized by NMR and high-resolution mass spectrometry. Their antioxidant activity was evaluated by hydroxyl radical scavenging assays (HRSA), and the anti-inflammatory potential was assessed via the inhibition of albumin denaturation (IAD). Lipophilicity was determined chromatographically. Molecular docking and 100 ns molecular dynamics simulations were performed to investigate the binding modes and stability in human serum albumin (HSA) binding sites. The acute toxicity of the hybrid molecules was predicted in silico using GUSAR software. Results: All synthesized hybrids demonstrated varying degrees of biological activity, with compound 3c exhibiting the most potent antioxidant (HRSA IC₅₀ = 71.13 µg/mL) and anti-inflammatory (IAD IC₅₀ = 108.58 µg/mL) effects. Lipophilicity assays indicated moderate membrane permeability, with compounds 3c and 3d showing favorable profiles. Docking studies revealed stronger binding affinities of S-enantiomers, particularly 3c and 3d, to Sudlow sites II and III in HSA. Molecular dynamics simulations confirmed stable ligand–protein complexes, highlighting compound 3c as maintaining consistent and robust interactions. The toxicity results indicate that most hybrids, particularly compounds 3b3d, exhibit a favorable safety profile compared to the parent trimetazidine. Conclusion: The hybrid trimetazidine–profen compounds synthesized herein, especially compound 3c, demonstrate promising dual antioxidant and anti-inflammatory therapeutic potential. Their stable interaction with serum albumin and balanced physicochemical properties support further development as novel agents for managing ischemic heart disease and associated inflammatory conditions. Full article
(This article belongs to the Special Issue Advances in the Medicinal Synthesis of Bioactive Compounds)
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22 pages, 10152 KB  
Review
The Role of Selected Myokines in the Development of Cardiovascular Diseases, and Their Involvement in Developing Heart Failure in Rheumatoid Arthritis Patients
by Jakub Kuna, Grzegorz Chmielewski, Łukasz Jaśkiewicz, Michalina Knapik and Magdalena Krajewska-Włodarczyk
Int. J. Mol. Sci. 2025, 26(17), 8194; https://doi.org/10.3390/ijms26178194 - 23 Aug 2025
Viewed by 516
Abstract
Cardiovascular diseases, which are among the most common diseases of the population and among the leading causes of death, are a constant topic of many research centers. A deeper understanding of their pathogenesis may contribute to the development of innovative diagnostic and therapeutic [...] Read more.
Cardiovascular diseases, which are among the most common diseases of the population and among the leading causes of death, are a constant topic of many research centers. A deeper understanding of their pathogenesis may contribute to the development of innovative diagnostic and therapeutic techniques. Recently, the role of myokines—a group of cytokines secreted mainly by muscle cells—has been increasingly emphasized in the development of these diseases. Both their excess and deficiency can cause undesirable effects that are involved in the pathomechanism of these diseases. In this review, we focus on the latest studies on the role of myonectin, irisin, musclin, follistatin-like1 (FSTL1), dermcidin, apelin, and myostatin in the pathogenesis of coronary artery disease, heart attack, heart failure, and hypertension. In particular, we look at myostatin and irisin in the context of the development of heart failure and decreased levels of apelin with higher cardiovascular risk in a group of patients with rheumatoid arthritis. Full article
(This article belongs to the Special Issue Molecular Mechanism in Cardiovascular Pathology)
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27 pages, 608 KB  
Review
Circulating Extracellular Vesicle-Based Biomarkers: Advances, Clinical Implications and Challenges in Coronary Artery Disease
by Valeria Carcia, Alessandro Vincenzo De Salve, Chiara Nonno and Maria Felice Brizzi
Int. J. Transl. Med. 2025, 5(3), 39; https://doi.org/10.3390/ijtm5030039 - 22 Aug 2025
Viewed by 412
Abstract
Coronary artery disease (CAD) is a leading cause of death worldwide, encompassing a broad spectrum of pathological conditions ranging from chronic to acute coronary syndromes. It underlies complex biological mechanisms, among which an emerging role is played by extracellular vesicles (EVs). EVs are [...] Read more.
Coronary artery disease (CAD) is a leading cause of death worldwide, encompassing a broad spectrum of pathological conditions ranging from chronic to acute coronary syndromes. It underlies complex biological mechanisms, among which an emerging role is played by extracellular vesicles (EVs). EVs are non-replicable cell-derived particles enclosed by lipid bilayers acting as mediators of cellular interactions. In the past two decades, there has been a growing interest in EVs as potential diagnostic, prognostic and therapeutic tools in cardiovascular disease. We reviewed the most recent studies on circulating EVs in CAD with a particular focus on their role in biomarker discovery. Our aim was to evaluate the feasibility of translating these findings into routine clinical practice. To this end, we underlie the development and application of integrated indicators, referred to as “Bioscores”, which combine clinical, laboratory, and molecular data to enhance diagnostic and prognostic accuracy. We briefly discuss the opportunity and pitfalls related to the emerging use of Machine Learning (ML) algorithms. Moreover, we highlight that further investigation of mechanistic pathways is required beyond the initially predicted associations generated by in silico studies. Finally, we analyzed the key limitations, challenges, and unmet needs in the field, including small and unrepresentative sample sizes, a lack of external validation, overlapping and often contradictory effects on targeted pathways, difficulties in standardizing EV isolation and characterization methods, as well as concerns regarding affordability and clinical reliability. Full article
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12 pages, 1069 KB  
Article
The Relationship Between Cardiac Syndrome X and Obstructive Sleep Apnea and the Effects of Sleep Apnea Treatment on Myocardial Ischemia
by Umit Ozturk, Beste Ozben, Mustafa Kursat Tigen, Baran Balcan, Tunc Ones, Gulin Sunter, Nuh Filizoglu, Murat Sunbul, Emre Gurel and Altug Cincin
J. Clin. Med. 2025, 14(16), 5897; https://doi.org/10.3390/jcm14165897 - 21 Aug 2025
Viewed by 309
Abstract
Background/Objectives: Cardiac Syndrome X (CSX) is associated with significant physical and psychiatric morbidity despite no obvious effect on long-term mortality. Obstructive sleep apnea (OSA) is a prevalent condition in close association with numerous cardiovascular diseases. The precise relation between CSX and OSA remains [...] Read more.
Background/Objectives: Cardiac Syndrome X (CSX) is associated with significant physical and psychiatric morbidity despite no obvious effect on long-term mortality. Obstructive sleep apnea (OSA) is a prevalent condition in close association with numerous cardiovascular diseases. The precise relation between CSX and OSA remains unclear. The aim of this study is to explore the relation between OSA and CSX, as well as the impact of continuous positive airway pressure (CPAP) therapy on myocardial ischemia. Methods: This single-center prospective cohort study examined patients who were selected consecutively from the Cardiology Outpatient Clinic with angina or angina-equivalent complaints and with ischemia on myocardial perfusion scintigraphy (MPS), and who were subsequently diagnosed with CSX via coronary angiography. Patients with previous myocardial infarction and previous percutaneous coronary intervention or coronary artery by-pass grafting surgery were excluded, since these conditions could not be regarded as CSX. The presence of OSA was explored by polysomnography (PSG). CPAP therapy was applied for three months to those diagnosed with OSA. Following a three-month course of treatment, a myocardial perfusion scintigraphy (MPS) was conducted, to assess myocardial ischemia. The IBM® SPSS Statistics Version 26 software was employed for the purpose of statistical analysis. Results: Among the 27 consecutive patients (mean age 58.1 ± 9.6 years and 22 female) with CSX 24 patients were found to have OSA according to PSG examination. CPAP therapy was applied to 17 patients (mean age 56.4 ± 8.6 years, 14 female) who accepted to participate in the treatment phase of the study. Following a three-month course of treatment, myocardial ischemia was reduced in 13 of the 17 patients. There were statistically significant correlations between the reduction in myocardial ischemia and patient’s diagnosis of hypertension (p = 0.006), higher serum HDL cholesterol levels (p = 0.009), and adherence to CPAP therapy (p = 0.047). Conclusions: The prevalence of OSA is significantly higher among the patients with CSX compared to the general adult population. In patients with CSX and OSA, improvement in myocardial ischemia was observed in MPS following CPAP therapy. Full article
(This article belongs to the Section Cardiology)
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13 pages, 269 KB  
Article
Association of Genetically Predicted Activity of AMP Deaminase 1 with Clinical and Biochemical Parameters in Diabetic Individuals with Coronary Artery Disease
by Maria Pietrzak-Nowacka, Ewa Gątarska, Krzysztof Safranow, Agnieszka Boroń, Kazimierz Ciechanowski, Jeremy S. C. Clark, Andrzej Ciechanowicz and Dorota Kostrzewa-Nowak
Int. J. Mol. Sci. 2025, 26(16), 8071; https://doi.org/10.3390/ijms26168071 - 21 Aug 2025
Viewed by 228
Abstract
Some reports indicated the association of rs17602729 and rs34526199 functional polymorphisms of the AMPD1 gene encoding adenosine monophosphate deaminase 1 (AMPD1) with the risk of coronary artery disease (CAD) and/or its intermediate phenotype. Therefore, the aim of our study was to analyze the [...] Read more.
Some reports indicated the association of rs17602729 and rs34526199 functional polymorphisms of the AMPD1 gene encoding adenosine monophosphate deaminase 1 (AMPD1) with the risk of coronary artery disease (CAD) and/or its intermediate phenotype. Therefore, the aim of our study was to analyze the association of both AMPD1 polymorphisms with the predisposition to disease and both clinical and biochemical phenotypes but solely in diabetic individuals with CAD. The study group consisted of 196 adult diabetic individuals with CAD, and the control group comprised 200 healthy newborns. Both AMPD1 polymorphisms were identified by a SNaPshot minisequencing reaction. Clinical and laboratory data were taken from patients’ records. There were no significant differences between both groups in the frequency distributions of AMPD1:rs17602729 and rs34526199 alleles or genotypes. BMI and the frequency of obesity in TT rs17602729 homozygotes (no AMPD1 activity) were significantly lower and the serum concentration of HDL cholesterol was significantly higher compared to other patients. The concentrations of total cholesterol and LDL cholesterol in homozygotes for wild-type AMPD1:rs17602729 (c.34C) and rs34526199 (c.860A) alleles (full AMPD1 activity) were significantly lower compared to its values in other patients. Our results suggest that genetically predicted activity of AMPD1 is associated with variation in body mass and lipid metabolism in diabetic Polish people with CAD. Full article
16 pages, 2267 KB  
Article
Placenta-Derived Mesenchymal Stem Cells (pMSCs) Reverse Diabetes-Associated Endothelial Complications in a Preclinical Animal Model
by Yasser Basmaeil, Ahmed Bakillah, Abdullah Mohammed Al Subayyil, Haya Nasser Bin Kulayb, Maha Abdullah AlRodayyan, Abeer Al Otaibi, Sindiyan Al Shaikh Mubarak, Hassan S. Alamri, Altaf A. Kondkar, Jahangir Iqbal and Tanvir Khatlani
Int. J. Mol. Sci. 2025, 26(16), 8057; https://doi.org/10.3390/ijms26168057 - 20 Aug 2025
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Abstract
Diabetes is increasingly recognized as a chronic inflammatory disease marked by systemic metabolic disturbances, with endothelial dysfunction playing a central role in its complications. Hyperglycemia, a hallmark of diabetes, drives endothelial damage by inducing excessive reactive oxygen species (ROS) production, particularly hydrogen peroxide [...] Read more.
Diabetes is increasingly recognized as a chronic inflammatory disease marked by systemic metabolic disturbances, with endothelial dysfunction playing a central role in its complications. Hyperglycemia, a hallmark of diabetes, drives endothelial damage by inducing excessive reactive oxygen species (ROS) production, particularly hydrogen peroxide (H2O2). This oxidative stress impairs endothelial cells, which are vital for vascular health, leading to severe complications such as diabetic nephropathy, retinopathy, and coronary artery disease—major causes of morbidity and mortality in diabetic patients. Recent studies have highlighted the therapeutic potential of placenta-derived mesenchymal stem cells (pMSCs), in mitigating these complications. pMSCs exhibit anti-inflammatory, antioxidant, and tissue-repair properties, showing promise in reversing endothelial damage in laboratory settings. To explore their efficacy in a more physiologically relevant context, we used a streptozotocin (STZ)-induced diabetic mouse model, which mimics type 1 diabetes by destroying pancreatic beta cells and causing hyperglycemia. pMSCs were administered via intra-peritoneal injections, and their effects on endothelial injury and tissue damage were assessed. Metabolic tests, including glucose tolerance tests (GTTs) and insulin tolerance tests (ITTs) revealed that pMSCs did not restore metabolic homeostasis or improve glucose regulation. However, histopathological kidney, heart, and eye tissue analyses demonstrated significant protective effects. pMSCs preserved glomerular structure in the kidneys, protected cardiac blood vessels, and maintained retinal integrity, suggesting their potential to address diabetes-related tissue injuries. Although these findings underscore the therapeutic potential of pMSCs for diabetic complications, further research is needed to optimize dosing, elucidate molecular mechanisms, and evaluate long-term safety and efficacy. Combining pMSCs with other therapies may enhance their benefits, paving the way for future clinical applications. Full article
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33 pages, 6066 KB  
Review
When Functional Assessment Meets Intravascular Imaging in Patients with Coronary Artery Disease
by Grigorios Tsigkas, Kassiani-Maria Nastouli, Anastasios Apostolos, Panagiota Spyropoulou, Maria Bozika, Michail I. Papafaklis, Stella Rouzi, Effrosyni Tsimara, Antonios Karanasos, Virginia Mplani and Periklis Davlouros
J. Cardiovasc. Dev. Dis. 2025, 12(8), 319; https://doi.org/10.3390/jcdd12080319 - 20 Aug 2025
Viewed by 811
Abstract
Percutaneous Coronary Intervention (PCI) has advanced significantly with the incorporation of imaging and physiology assessment techniques. Fractional Flow Reserve (FFR) and Non-Hyperemic Pressure indices (NHPIs) provide information regarding the functional significance of coronary lesions, while Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) [...] Read more.
Percutaneous Coronary Intervention (PCI) has advanced significantly with the incorporation of imaging and physiology assessment techniques. Fractional Flow Reserve (FFR) and Non-Hyperemic Pressure indices (NHPIs) provide information regarding the functional significance of coronary lesions, while Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) enhance anatomical characterization and guide stent implantation. This review explores the implementation of physiology- and imaging-guided strategies in clinical practice, comparing their efficacy and limitations. Novel technologies now allow for physiology estimation without hyperemic agents, and hybrid techniques, such as OCT-derived FFR, are increasingly integrated into clinical practice. These approaches offer the combined advantages of functional assessment and detailed anatomical imaging. Full article
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