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Keywords = heart-type fatty-acid-binding protein

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21 pages, 1487 KB  
Review
Beyond a Single Marker: An Update on the Comprehensive Evaluation of Right Ventricular Dysfunction in Pulmonary Thromboembolism
by Sandu Cucută, Minerva Codruta Badescu, Ștefania-Teodora Duca, Adriana Chetran, Maria-Ruxandra Cepoi, Cosmina-Georgiana Ponor, Amelian Madalin Bobu, Ionela-Lacramioara Serban and Irina-Iuliana Costache-Enache
Life 2025, 15(4), 665; https://doi.org/10.3390/life15040665 - 17 Apr 2025
Viewed by 838
Abstract
Pulmonary thromboembolism (PE) is a life-threatening condition that often leads to right ventricular (RV) dysfunction, a key determinant of prognosis and clinical management. Biomarkers play a crucial role in the early detection and risk stratification of RV dysfunction in PE, complementing imaging and [...] Read more.
Pulmonary thromboembolism (PE) is a life-threatening condition that often leads to right ventricular (RV) dysfunction, a key determinant of prognosis and clinical management. Biomarkers play a crucial role in the early detection and risk stratification of RV dysfunction in PE, complementing imaging and hemodynamic assessments. Cardiac troponins, B-type natriuretic peptides, and novel biomarkers, such as heart-type fatty acid-binding protein (H-FABP) and growth differentiation factor-15 (GDF-15), provide valuable insights into myocardial injury, overload, and stress. This article explores the clinical possible significance of these biomarkers, their predictive value, and their potential to guide therapeutic strategies in patients with PE. Understanding the role of biomarkers in RV dysfunction assessment may improve patient outcomes focusing on early intervention and personalized treatment approaches. Full article
(This article belongs to the Section Physiology and Pathology)
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14 pages, 547 KB  
Article
Evaluation of Thrombomodulin, Heart-Type Fatty-Acid-Binding Protein, Pentraxin-3 and Galectin-3 Levels in Patients with Myocardial Infarction, with and Without ST Segment Elevation
by Naile Fevziye Misirlioglu, Gulbahar Guler Orucoglu, Burcu Bıcakhan, Suat Hayri Kucuk, Solen Himmetoglu, Sena Baykara Sayili, Gulenay Defne Ozen and Hafize Uzun
J. Clin. Med. 2025, 14(3), 1015; https://doi.org/10.3390/jcm14031015 - 5 Feb 2025
Cited by 1 | Viewed by 1178
Abstract
Background: Medical history, ECG findings and cardiac markers are used in the diagnosis of myocardial infarction (MI). Biomarkers used especially for the diagnosis of MI include high-sensitivity troponins (hsTns), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), myoglobin, cardiac myosin-binding protein C and new cardiac [...] Read more.
Background: Medical history, ECG findings and cardiac markers are used in the diagnosis of myocardial infarction (MI). Biomarkers used especially for the diagnosis of MI include high-sensitivity troponins (hsTns), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), myoglobin, cardiac myosin-binding protein C and new cardiac biomarkers. This study evaluated the levels of serum thrombomodulin (TM), heart-type fatty-acid-binding protein (H-FABP), pentraxin-3 (PTX-3) and galectin-3 (Gal-3) to determine their utility in distinguishing between ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). Methods: This study included a total of 180 patients (90 patients with acute STEMI and 90 patients with NSTEMI) who presented to the Gaziosmanpaşa Training and Research Hospital, Cardiovascular Surgery and Emergency Department, with ischemic chest pain lasting longer than 30 min. Ninety healthy volunteers were included as the control group. Results: Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), TM, H-FABP, PTX-3 and Gal-3 were significantly different across the STEMI, NSTEMI and control groups (p < 0.001). Strong positive correlations were observed between NT-proBNP and TM, H-FABP, PTX-3 and Gal-3 in the STEMI group. ROC analysis demonstrated excellent diagnostic accuracy for these biomarkers in distinguishing STEMI from NSTEMI and control groups. Conclusions: Vascular inflammation plays an important role in the pathophysiology of STEMI and NSTEMI. A comprehensive cardiac biomarker panel enhances diagnostic accuracy and risk stratification, particularly when distinguishing between STEMI and NSTEMI. The biomarkers hs-TnI, CK-MB, NT-proBNP, TM, H-FABP, PTX-3 and Gal-3 offer complementary information when used together as a panel. Further research and validation are essential to establish standardized protocols for their widespread use. Full article
(This article belongs to the Section Cardiovascular Medicine)
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11 pages, 798 KB  
Article
Novel Biomarkers as Potential Predictors of Decompensated Advanced Chronic Heart Failure—Single Center Study
by Tobias Fröhling, Dilvin Semo, Moritz Mirna, Vera Paar, Zornitsa Shomanova, Lukas J. Motloch, Andreas Rukosujew, Jürgen R. Sindermann, Michael Lichtenauer and Rudin Pistulli
J. Clin. Med. 2024, 13(22), 6866; https://doi.org/10.3390/jcm13226866 - 14 Nov 2024
Viewed by 1463
Abstract
Background/Objectives: Heart failure (HF) remains a major therapeutic and diagnostic challenge nowadays. Albeit, acute decompensated HF is associated with several clinical signs such as dyspnea or edema, it remains a challenge to use easy accessible and suitable tools, such as biomarkers, to distinguish [...] Read more.
Background/Objectives: Heart failure (HF) remains a major therapeutic and diagnostic challenge nowadays. Albeit, acute decompensated HF is associated with several clinical signs such as dyspnea or edema, it remains a challenge to use easy accessible and suitable tools, such as biomarkers, to distinguish between patients at risk for an acute decompensation of their heart failure and compensated, stable HF patients. Existing biomarkers, such as natriuretic peptides or troponin, are not specific and can be elevated due to several other disease conditions, such as myocardial infarction, atrial fibrillation, or valve diseases. Therefore, the aim of this study was to analyze the predictive potential of four novel cardiovascular biomarkers—the soluble urokinase-type plasminogen activator receptor (suPAR), heart-type fatty acid binding protein (H-FABP), vascular cell adhesion molecule 1 (VCAM-1), and growth/differentiation factor 15 (GDF-15) for the detection of cardiac decompensation in patients with HF. Methods: In this study, 146 patients were prospectively enrolled and the serum biomarker concentrations were analyzed using Enzyme Linked Immunosorbent Assay (ELISA). We correlated the biomarker concentrations with clinical and biochemical parameters of all patients and the predictive value for detection of cardiac decompensation was assessed. Results: A significant increase in the levels of suPAR (1.6-fold-change, p < 0.0001), H-FABP (2.2-fold-change, p = 0.0458), VCAM-1 (1.6-fold-change, p < 0.0001), and GDF-15 (1.7-fold-change, p = 0.0009) was detected in all patients with acute decompensated HF in comparison to patients with compensated HF. Univariate logistic regression analysis revealed a significant association of biomarker plasma concentration with the risk for a cardiac decompensation (suPAR: p < 0.0001; VCAM-1: p < 0.0001, H-FABP: p = 0.0458; GDF-15: p = 0.0009). Conclusions: In conclusion, the investigated novel cardiovascular biomarkers suPAR, GDF-15, VCAM-1, and H-FABP could be a valuable tool to facilitate therapeutic decisions in patients with heart failure and suspicion of a cardiac decompensation. Parameters such as renal function should be taken into account. Further studies on novel biomarkers are required to find reliable, sensitive, and specific tools that will enable the early detection of patients with acute decompensation. Full article
(This article belongs to the Section Cardiology)
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17 pages, 5113 KB  
Article
The Impact of Normobaric Hypoxia and Intermittent Hypoxic Training on Cardiac Biomarkers in Endurance Athletes: A Pilot Study
by Jakub Goliniewski, Miłosz Czuba, Kamila Płoszczyca, Małgorzata Chalimoniuk, Robert Gajda, Adam Niemaszyk, Katarzyna Kaczmarczyk and Józef Langfort
Int. J. Mol. Sci. 2024, 25(9), 4584; https://doi.org/10.3390/ijms25094584 - 23 Apr 2024
Viewed by 3475
Abstract
This study explores the effects of normobaric hypoxia and intermittent hypoxic training (IHT) on the physiological condition of the cardiac muscle in swimmers. Hypoxia has been reported to elicit both beneficial and adverse changes in the cardiovascular system, but its impact on the [...] Read more.
This study explores the effects of normobaric hypoxia and intermittent hypoxic training (IHT) on the physiological condition of the cardiac muscle in swimmers. Hypoxia has been reported to elicit both beneficial and adverse changes in the cardiovascular system, but its impact on the myocardium during acute exercise and altitude/hypoxic training remains less understood. We aimed to determine how a single bout of intense interval exercise and a four-week period of high-intensity endurance training under normobaric hypoxia affect cardiac marker activity in swimmers. Sixteen young male swimmers were divided into two groups: one undergoing training in hypoxia and the other in normoxia. Cardiac markers, including troponin I and T (cTnI and cTnT), heart-type fatty acid-binding protein (H-FABP), creatine kinase-MB isoenzyme (CK-MB), and myoglobin (Mb), were analyzed to assess the myocardium’s response. We found no significant differences in the physiological response of the cardiac muscle to intense physical exertion between hypoxia and normoxia. Four weeks of IHT did not alter the resting levels of cTnT, cTnI, and H-FABP, but it resulted in a noteworthy decrease in the resting concentration of CK-MB, suggesting enhanced cardiac muscle adaptation to exercise. In contrast, a reduction in resting Mb levels was observed in the control group training in normoxia. These findings suggest that IHT at moderate altitudes does not adversely affect cardiac muscle condition and may support cardiac muscle adaptation, affirming the safety and efficacy of IHT as a training method for athletes. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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15 pages, 984 KB  
Article
Post-Coronary Artery Bypass Grafting Outcomes of Patients with/without Type-2 Diabetes Mellitus and Chronic Kidney Disease Treated with SGLT2 Inhibitor Dapagliflozin: A Single-Center Experience Analysis
by Razan Al Namat, Letiția Doina Duceac, Liliana Chelaru, Marius Gabriel Dabija, Cristian Guțu, Constantin Marcu, Maria Valentina Popa, Florina Popa, Elena Roxana Bogdan Goroftei and Elena Țarcă
Diagnostics 2024, 14(1), 16; https://doi.org/10.3390/diagnostics14010016 - 21 Dec 2023
Cited by 11 | Viewed by 2839
Abstract
Introduction: Increasingly, SGLT2 inhibitors save patients with heart failure and comorbidities such as type-2 diabetes mellitus (T2DM) and chronic kidney disease (CKD); the inhibition of sodium-glucose cotransporter 2 (SGLT2) was first studied in patients with diabetes as a solution to lower glucose levels [...] Read more.
Introduction: Increasingly, SGLT2 inhibitors save patients with heart failure and comorbidities such as type-2 diabetes mellitus (T2DM) and chronic kidney disease (CKD); the inhibition of sodium-glucose cotransporter 2 (SGLT2) was first studied in patients with diabetes as a solution to lower glucose levels by preventing glucose reabsorption and facilitating its elimination; in the process, researchers took notice of how SGLT2 inhibitors also seemed to have beneficial cardiovascular effects in patients with both diabetes and cardiovascular disease. Aim: Our single-center prospective study assesses outcomes of post-coronary artery bypass grafting (CABG) rehabilitation and SLGT2 inhibition in CABG patients with/without T2DM and with/without CKD. Materials and Methods: One hundred twenty consecutive patients undergoing CABG were included in the analysis. Patients were divided into four subgroups: diabetes patients with chronic kidney disease (T2DM + CKD), diabetes patients without chronic kidney disease (T2DM−CKD), prediabetes patients with chronic kidney disease (PreD+CKD), and prediabetes patients without chronic kidney disease (PreD−CKD). Echocardiographic and laboratory investigations post-surgery (phase I) and 6 months later (phase II) included markers for cardiac ischemia, glycemic status, and renal function, and metabolic equivalents were investigated. Results: One hundred twenty patients participated, mostly men, overweight/obese, hypertensive, smokers; 65 had T2DM (18 with CKD), and 55 were prediabetic (17 with CKD). The mean ejection fraction increased by 8.43% overall but significantly more in the prediabetes group compared to the T2DM group (10.14% vs. 6.98%, p < 0.05). Overall, mean heart-type fatty-acid-binding protein (H-FABP) levels returned to normal levels, dropping from 68.40 ng/mL to 4.82 ng/mL (p = 0.000), and troponin data were more nuanced relative to an overall, strongly significant decrease of 44,458 ng/L (p = 0.000). Troponin levels in patients with CKD dropped more, both in the presence of T2DM (by 82,500 ng/L, p = 0.000) and in patients without T2DM (by 73,294 ng/L, p = 0.047). As expected, the overall glycated hemoglobin (HbA1c) levels improved significantly in those with prediabetes (from 6.54% to 5.55%, p = 0.000); on the other hand, the mean HbA1c changed from 7.06% to 6.06% (p = 0.000) in T2DM, and the presence or absence of CKD did not seem to make any difference: T2DM+CKD 7.01–6.08% (p = 0.000), T2DM−CKD 7.08–6.04% (p = 0.000), PreD+CKD 5.66–4.98% (p = 0.014), and PreD−CKD 6.03–4.94% (p = 0.00). Compared to an overall gain of 11.51, the GFRs of patients with CKD improved by 18.93 (68.15–87.07%, p = 0.000) in the presence of established diabetes and 14.89 (64.75–79.64%, p = 0.000) in the prediabetes group. Conclusions: Regarding the patients’ cardiac statuses, the results from our single-center analysis revealed a significant decrease in ischemic risk (H-FABP and hs-cTnI levels) with improvements in mean ejection fraction, glycemic status, and renal function in patients post-CABG with/without T2DM, with/without CKD, and with SGLT2 inhibitor dapagliflozin treatment while undergoing cardiac rehabilitation. Full article
(This article belongs to the Special Issue New Advance in Central and Peripheral Circulation in Diabetes)
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15 pages, 2879 KB  
Article
A Methylene Blue-Enhanced Nanostructured Electrochemical Immunosensor for H-FABP Myocardial Injury Biomarker
by Cecília Maciel Prado, Paula Angélica Burgos Ferreira, Lucas Alves de Lima, Erika Ketlem Gomes Trindade and Rosa Fireman Dutra
Biosensors 2023, 13(9), 873; https://doi.org/10.3390/bios13090873 - 7 Sep 2023
Cited by 5 | Viewed by 2409
Abstract
A sensitive electrochemical immunosensor for the detection of the heart-type fatty acid binding protein (HFABP), an earlier biomarker for acute myocardial infarction than Troponins, is described. The sensing platform was enhanced with methylene blue (MB) redox coupled to carbon nanotubes (CNT) assembled on [...] Read more.
A sensitive electrochemical immunosensor for the detection of the heart-type fatty acid binding protein (HFABP), an earlier biomarker for acute myocardial infarction than Troponins, is described. The sensing platform was enhanced with methylene blue (MB) redox coupled to carbon nanotubes (CNT) assembled on a polymer film of polythionine (PTh). For this strategy, monomers of thionine rich in amine groups were electrosynthesized by cyclic voltammetry on the immunosensor’s gold surface, forming an electroactive film with excellent electron transfer capacity. Stepwise sensor surface preparation was electrochemically characterized at each step and scanning electronic microscopy was carried out showing all the preparation steps. The assembled sensor platform combines MB and PTh in a synergism, allowing sensitive detection of the H-FABP in a linear response from 3.0 to 25.0 ng∙mL−1 with a limit of detection of 1.47 ng∙mL−1 HFABP that is similar to the clinical level range for diagnostics. H-FABP is a newer powerful biomarker for distinguishing between unstable angina and acute myocardial infarction. Full article
(This article belongs to the Special Issue Nanomaterial Based Biosensors for Biomedical Applications)
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17 pages, 2333 KB  
Review
The Function of MondoA and ChREBP Nutrient—Sensing Factors in Metabolic Disease
by Byungyong Ahn
Int. J. Mol. Sci. 2023, 24(10), 8811; https://doi.org/10.3390/ijms24108811 - 16 May 2023
Cited by 8 | Viewed by 3787
Abstract
Obesity is a major global public health concern associated with an increased risk of many health problems, including type 2 diabetes, heart disease, stroke, and some types of cancer. Obesity is also a critical factor in the development of insulin resistance and type [...] Read more.
Obesity is a major global public health concern associated with an increased risk of many health problems, including type 2 diabetes, heart disease, stroke, and some types of cancer. Obesity is also a critical factor in the development of insulin resistance and type 2 diabetes. Insulin resistance is associated with metabolic inflexibility, which interferes with the body’s ability to switch from free fatty acids to carbohydrate substrates, as well as with the ectopic accumulation of triglycerides in non-adipose tissue, such as that of skeletal muscle, the liver, heart, and pancreas. Recent studies have demonstrated that MondoA (MLX-interacting protein or MLXIP) and the carbohydrate response element-binding protein (ChREBP, also known as MLXIPL and MondoB) play crucial roles in the regulation of nutrient metabolism and energy homeostasis in the body. This review summarizes recent advances in elucidating the function of MondoA and ChREBP in insulin resistance and related pathological conditions. This review provides an overview of the mechanisms by which MondoA and ChREBP transcription factors regulate glucose and lipid metabolism in metabolically active organs. Understanding the underlying mechanism of MondoA and ChREBP in insulin resistance and obesity can foster the development of new therapeutic strategies for treating metabolic diseases. Full article
(This article belongs to the Special Issue Advances in Insulin Resistance)
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12 pages, 723 KB  
Communication
Urinary Biomarkers in a Living Donor Kidney Transplantation Cohort—Predictive Value on Graft Function
by G. J. Julia Huisman, Nora A. Spraakman, Jeroen V. Koomen, A. Marrit Talsma, Robert A. Pol, Stefan P. Berger, Henri G. D. Leuvenink, Michel M. R. F. Struys and Gertrude J. Nieuwenhuijs-Moeke
Int. J. Mol. Sci. 2023, 24(6), 5649; https://doi.org/10.3390/ijms24065649 - 15 Mar 2023
Cited by 2 | Viewed by 2220
Abstract
Early non-invasive detection and prediction of graft function after kidney transplantation is essential since interventions might prevent further deterioration. The aim of this study was to analyze the dynamics and predictive value of four urinary biomarkers: kidney injury molecule-1 (KIM-1), heart-type fatty acid [...] Read more.
Early non-invasive detection and prediction of graft function after kidney transplantation is essential since interventions might prevent further deterioration. The aim of this study was to analyze the dynamics and predictive value of four urinary biomarkers: kidney injury molecule-1 (KIM-1), heart-type fatty acid binding protein (H-FABP), N-acetyl-β-D-glucosaminidase (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) in a living donor kidney transplantation (LDKT) cohort. Biomarkers were measured up to 9 days after the transplantation of 57 recipients participating in the VAPOR-1 trial. Dynamics of KIM-1, NAG, NGAL, and H-FABP significantly changed over the course of 9 days after transplantation. KIM-1 at day 1 and NAG at day 2 after transplantation were significant predictors for the estimated glomerular filtration rate (eGFR) at various timepoints after transplantation with a positive estimate (p < 0.05), whereas NGAL and NAG at day 1 after transplantation were negative significant predictors (p < 0.05). Multivariable analysis models for eGFR outcome improved after the addition of these biomarker levels. Several donor, recipient and transplantation factors significantly affected the baseline of urinary biomarkers. In conclusion, urinary biomarkers are of added value for the prediction of graft outcome, but influencing factors such as the timing of measurement and transplantation factors need to be considered. Full article
(This article belongs to the Special Issue New Generation Biomarkers in Kidney Transplantation)
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21 pages, 4213 KB  
Article
Heart-Type Fatty Acid Binding Protein Binds Long-Chain Acylcarnitines and Protects against Lipotoxicity
by Diana Zelencova-Gopejenko, Melita Videja, Aiga Grandane, Linda Pudnika-Okinčica, Anda Sipola, Karlis Vilks, Maija Dambrova, Kristaps Jaudzems and Edgars Liepinsh
Int. J. Mol. Sci. 2023, 24(6), 5528; https://doi.org/10.3390/ijms24065528 - 14 Mar 2023
Cited by 9 | Viewed by 2889
Abstract
Heart-type fatty-acid binding protein (FABP3) is an essential cytosolic lipid transport protein found in cardiomyocytes. FABP3 binds fatty acids (FAs) reversibly and with high affinity. Acylcarnitines (ACs) are an esterified form of FAs that play an important role in cellular energy metabolism. However, [...] Read more.
Heart-type fatty-acid binding protein (FABP3) is an essential cytosolic lipid transport protein found in cardiomyocytes. FABP3 binds fatty acids (FAs) reversibly and with high affinity. Acylcarnitines (ACs) are an esterified form of FAs that play an important role in cellular energy metabolism. However, an increased concentration of ACs can exert detrimental effects on cardiac mitochondria and lead to severe cardiac damage. In the present study, we evaluated the ability of FABP3 to bind long-chain ACs (LCACs) and protect cells from their harmful effects. We characterized the novel binding mechanism between FABP3 and LCACs by a cytotoxicity assay, nuclear magnetic resonance, and isothermal titration calorimetry. Our data demonstrate that FABP3 is capable of binding both FAs and LCACs as well as decreasing the cytotoxicity of LCACs. Our findings reveal that LCACs and FAs compete for the binding site of FABP3. Thus, the protective mechanism of FABP3 is found to be concentration dependent. Full article
(This article belongs to the Special Issue Modulation of Protein Structure and Function by Lipids)
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13 pages, 984 KB  
Article
Fatty Acid Binding Proteins 3 and 4 Predict Both All-Cause and Cardiovascular Mortality in Subjects with Chronic Heart Failure and Type 2 Diabetes Mellitus
by Ricardo Rodríguez-Calvo, Minerva Granado-Casas, Alejandra Pérez-Montes de Oca, María Teresa Julian, Mar Domingo, Pau Codina, Evelyn Santiago-Vacas, Germán Cediel, Josep Julve, Joana Rossell, Lluís Masana, Didac Mauricio, Josep Lupón, Antoni Bayes-Genis and Núria Alonso
Antioxidants 2023, 12(3), 645; https://doi.org/10.3390/antiox12030645 - 4 Mar 2023
Cited by 9 | Viewed by 2909
Abstract
Subjects with type 2 diabetes mellitus (T2D) are at increased risk for heart failure (HF). The cardiac-specific (FABP3) and adipose-tissue-specific (FABP4) types of the fatty acid binding proteins have been associated with both all-cause and cardiovascular (CV) mortality. The aim of this study [...] Read more.
Subjects with type 2 diabetes mellitus (T2D) are at increased risk for heart failure (HF). The cardiac-specific (FABP3) and adipose-tissue-specific (FABP4) types of the fatty acid binding proteins have been associated with both all-cause and cardiovascular (CV) mortality. The aim of this study was to explore the prognosis value of FABP3 and FABP4 in ambulatory subjects with chronic HF (CHF), with and without T2D. A prospective study involving 240 ambulatory CHF subjects was performed. Patients were followed-up for a mean of 5.78 ± 3.30 years and cause of death (if any) was recorded. Primary endpoints were defined as all-cause and CV death, and a composite endpoint that included CV death or hospitalization for HF was included as a secondary endpoint. Baseline serum samples were obtained and the serum FABP3 and FABP4 concentrations were assessed by sandwich enzyme-linked immunosorbent assay. Survival analysis was performed with multivariable Cox regressions, using Fine and Gray competing risks models when needed, to explore the prognostic value of FABP3 and FABP4 concentrations, adjusting for potential confounders. Type 2 diabetes mellitus was highly prevalent, accounting for 47.5% for total subjects with CHF. Subjects with T2D showed higher mortality rates (T2D: 69.30%; non-T2D: 50.79%, p = 0.004) and higher serum FABP3 (1829.3 (1104.9–3440.5) pg/mL vs. 1396.05 (820.3–2362.16) pg/mL, p = 0.007) and FABP4 (45.5 (27.6–79.8) ng/mL vs. 34.1 (24.09–55.3) ng/mL, p = 0.006) concentrations compared with non-T2D CHF subjects. In the whole study cohort, FABP3 was independently associated with all-cause death, and both FABP3 and FABP4 concentrations were associated with CV mortality. The predictive values of these two molecules for all-cause (FABP3: HR 1.25, 95% CI 1.09–1.44; p = 0.002. FABP4: HR 2.21, 95% CI 1.12–4.36; p = 0.023) and CV mortality (FABP3: HR 1.28, 95% CI 1.09–1.50; p = 0.002. FABP4: HR 4.19, 95% CI 2.21–7.95; p < 0.001) were only statistically significant in the subgroup of subjects with T2D. Notably, FABP4 (HR 2.07, 95% CI 1.11–3.87; p = 0.022), but not FABP3, also predicted the occurrence of the composite endpoint (death or hospitalization for HF) only in subjects with T2D. All these associations were not found in CHF subjects without T2D. Our findings support the usefulness of serum FABP3 and FABP4 concentrations as independent predictors for the occurrence of all-cause and CV mortality in ambulatory subjects with CHF with T2D. Full article
(This article belongs to the Special Issue Lipid-Binding Proteins and Oxidative Stress in Health and Disease)
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13 pages, 1684 KB  
Article
The Presence of Ascending Aortic Dilatation in Patients Undergoing Transcatheter Aortic Valve Replacement Is Negatively Correlated with the Presence of Diabetes Mellitus and Does Not Impair Post-Procedural Outcomes
by Elke Boxhammer, Stefan Hecht, Reinhard Kaufmann, Jürgen Kammler, Jörg Kellermair, Christian Reiter, Kaveh Akbari, Hermann Blessberger, Clemens Steinwender, Michael Lichtenauer, Uta C. Hoppe, Klaus Hergan and Bernhard Scharinger
Diagnostics 2023, 13(3), 358; https://doi.org/10.3390/diagnostics13030358 - 18 Jan 2023
Cited by 1 | Viewed by 3013
Abstract
Both relevant aortic valve stenosis (AS) and aortic valve insufficiency significantly contribute to structural changes in the ascending aorta (AA) and thus to its dilatation. In patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), survival data regarding aortic changes and laboratory [...] Read more.
Both relevant aortic valve stenosis (AS) and aortic valve insufficiency significantly contribute to structural changes in the ascending aorta (AA) and thus to its dilatation. In patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), survival data regarding aortic changes and laboratory biomarker analyses are scarce. Methods: A total of 179 patients with severe AS and an available computed tomography were included in this retrospective study. AA was measured, and dilatation was defined as a diameter ≥ 40 mm. Thirty-two patients had dilatation of the AA. A further 32 patients from the present population with a normal AA were matched to the aortic dilatation group with respect to gender, age, body mass index and body surface area, and the resulting study groups were compared with each other. In addition to echocardiographic and clinical characteristics, the expression of cardiovascular biomarkers such as brain natriuretic peptide (BNP), soluble suppression of tumorigenicity-2 (sST2), growth/differentiation of factor-15 (GDF-15), heart-type fatty-acid binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2) and soluble urokinase-type plasminogen activator receptor (suPAR) was analyzed. Kaplan–Meier curves for short- and long-term survival were obtained, and Pearson’s and Spearman’s correlations were calculated to identify the predictors between the diameter of the AA and clinical parameters. Results: A total of 19% of the total cohort had dilatation of the AA. The study group with an AA diameter ≥ 40 mm showed a significantly low comorbidity with respect to diabetes mellitus in contrast to the comparison cohort with an AA diameter < 40 mm (p = 0.010). This result continued in the correlation analyses performed, as the presence of diabetes mellitus correlated negatively not only with the diameter of the AA (r = −0.404; p = 0.001) but also with the presence of aortic dilatation (r = −0.320; p = 0.010). In addition, the presence of AA dilatation after TAVR was shown to have no differences in terms of patient survival at 1, 3 and 5 years. There were no relevant differences in the cardiovascular biomarkers studied between the patients with dilated and normal AAs. Conclusion: The presence of AA dilatation before successful TAVR was not associated with a survival disadvantage at the respective follow-up intervals of 1, 3 and 5 years. Diabetes mellitus in general seemed to have a protective effect against the development of AA dilatation or aneurysm in patients with severe AS. Full article
(This article belongs to the Collection Vascular Diseases Diagnostics)
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20 pages, 3376 KB  
Article
A Story of PA/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis—The Rise of IGF-BP2 and GDF-15
by Joseph Kletzer, Stefan Hecht, Susanne Ramsauer, Bernhard Scharinger, Reinhard Kaufmann, Jürgen Kammler, Jörg Kellermair, Kaveh Akbari, Hermann Blessberger, Clemens Steinwender, Klaus Hergan, Uta C. Hoppe, Michael Lichtenauer and Elke Boxhammer
J. Cardiovasc. Dev. Dis. 2023, 10(1), 22; https://doi.org/10.3390/jcdd10010022 - 5 Jan 2023
Cited by 3 | Viewed by 3027
Abstract
(1) Background: Currently, echocardiography is the primary non-invasive diagnostic method used to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). Other radiological methods have been a focus of research in the past [...] Read more.
(1) Background: Currently, echocardiography is the primary non-invasive diagnostic method used to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). Other radiological methods have been a focus of research in the past couple of years, as it was shown that by determining the pulmonary artery (PA) diameter, prognostic statements concerning overall mortality could be made in these patients. This study compared established and novel cardiovascular biomarkers with the PA/BSA value to detect PH in patients with severe AS. (2) Methods: The study cohort comprised 188 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), who were then divided into two groups based on PA/BSA values obtained through CT-angiography. The presence of PH was defined as a PA/BSA ≥ 16.6 mm/m2 (n = 81), and absence as a PA/BSA < 16.6 mm/m2 (n = 107). Blood samples were taken before TAVR to assess cardiovascular biomarkers used in this study, namely brain natriuretic peptide (BNP), cardiac troponin I (cTnI), high-sensitive troponin (hsTN), soluble suppression of tumorigenesis-2 (sST2), growth/differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2), and soluble urokinase-type plasminogen activator receptor (suPAR). (3) Results: Patients with a PA/BSA ≥ 16.6 mm/m2 showed significantly higher levels of BNP (p = <0.001), GDF-15 (p = 0.040), and H-FABP (p = 0.007). The other investigated cardiovascular biomarkers did not significantly differ between the two groups. To predict a PA/BSA ≥ 16.6 mm/m2, cut-off values for the biomarkers were calculated. Here, GDF-15 (p = 0.029; cut-off 1172.0 pg/mL) and BNP (p < 0.001; cut-off 2194.0 pg/mL) showed significant results. Consequently, analyses of combined biomarkers were performed, which yielded IGF-BP2 + BNP (AUC = 0.721; 95%CI = 0.585–0.857; p = 0.004) as the best result of the two-way analyses and GDF-15 + IGF-BP2 + BNP (AUC = 0.727; 95%CI = 0.590–0.864; p = 0.004) as the best result of the three-way analyses. No significant difference regarding the 1-year survival between patients with PA/BSA < 16.6 mm/m2 and patients with PA/BSA ≥ 16.6 mm/m2 was found (log-rank test: p = 0.452). (4) Conclusions: Although PA/BSA aims to reduce the bias of the PA value caused by different body compositions and sizes, it is still a controversial parameter for diagnosing PH. Combining the parameter with different cardiovascular biomarkers did not lead to a significant increase in the diagnostic precision for detecting PH in patients with severe AS. Full article
(This article belongs to the Special Issue New Perspectives on Pulmonary Hypertension (PH))
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18 pages, 3789 KB  
Article
Deficiency of Adipose Triglyceride Lipase Induces Metabolic Syndrome and Cardiomyopathy in Zebrafish
by Hsin-Hung Lai, Kun-Yun Yeh, Hung-Ming Hsu and Guor Mour Her
Int. J. Mol. Sci. 2023, 24(1), 117; https://doi.org/10.3390/ijms24010117 - 21 Dec 2022
Cited by 9 | Viewed by 3588
Abstract
Lipid metabolism dysfunction is related to clinical disorders including obesity, cancer, liver steatosis, and cardiomyopathy. Impaired lipolytic enzymes result in altered release of free fatty acids. The dramatic change in dyslipidemia is important in lipotoxic cardiomyopathy. Adipose triglyceride lipase (ATGL) catalyzes the lipolysis [...] Read more.
Lipid metabolism dysfunction is related to clinical disorders including obesity, cancer, liver steatosis, and cardiomyopathy. Impaired lipolytic enzymes result in altered release of free fatty acids. The dramatic change in dyslipidemia is important in lipotoxic cardiomyopathy. Adipose triglyceride lipase (ATGL) catalyzes the lipolysis of triacylglycerol to reduce intramyocardial triglyceride levels in the heart and improve myocardial function. We examined the role of ATGL in metabolic cardiomyopathy by developing an Atgl knockout (ALKO) zebrafish model of metabolic cardiomyopathy disease by continuously expressing CRISPR/Cas9 protein and atgl gene guide RNAs (gRNAs). The expressed Cas9 protein bound to four gRNAs targeting the atgl gene locus, facilitating systemic gene KO. Ablation of Atgl interfered with lipid metabolism, which induced hyperlipidemia and hyperglycemia. ALKO adults and embryos displayed hypertrophic hearts. ALKO presented a typical dilated cardiomyopathy profile with a remarkable reduction in four sarcomere genes (myosin heavy chain 7-like, actin alpha cardiac muscle 1b, myosin binding protein C3, and troponin T type 2a) and two Ca2+ handling regulator genes (tropomyosin 4b and ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2b). Immune cell infiltration in cardiac tissue of ALKO provided direct evidence of advanced metabolic cardiomyopathy. The presently described model could become a powerful tool to clarify the underlying mechanism between metabolic disorders and cardiomyopathies. Full article
(This article belongs to the Special Issue Zebrafish as a Model in Human Disease)
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17 pages, 1835 KB  
Article
CT-Diagnosed Sarcopenia and Cardiovascular Biomarkers in Patients Undergoing Transcatheter Aortic Valve Replacement: Is It Possible to Predict Muscle Loss Based on Laboratory Tests?—A Multicentric Retrospective Analysis
by Stefan Hecht, Elke Boxhammer, Reinhard Kaufmann, Bernhard Scharinger, Christian Reiter, Jürgen Kammler, Jörg Kellermair, Matthias Hammerer, Hermann Blessberger, Clemens Steinwender, Uta C. Hoppe, Klaus Hergan and Michael Lichtenauer
J. Pers. Med. 2022, 12(9), 1453; https://doi.org/10.3390/jpm12091453 - 4 Sep 2022
Cited by 3 | Viewed by 2605
Abstract
Background: Patients with severe aortic valve stenosis (AS) often present with heart failure and sarcopenia. Sarcopenia, described as progressive degradation of skeletal muscle mass, has frequently been implicated as a cause of increased mortality, prolonged hospitalization and generalized poor outcome after transcatheter aortic [...] Read more.
Background: Patients with severe aortic valve stenosis (AS) often present with heart failure and sarcopenia. Sarcopenia, described as progressive degradation of skeletal muscle mass, has frequently been implicated as a cause of increased mortality, prolonged hospitalization and generalized poor outcome after transcatheter aortic valve replacement (TAVR). At present, sarcopenia is defined by the European Working Group on Sarcopenia in Older People (EWGSOP) based on clinical examination criteria and radiological imaging. The aim of the present study was to compare patients with Computed Tomography (CT)-diagnosed sarcopenia with regard to the expression of cardiovascular biomarkers in order to obtain additional, laboratory-chemical information. Methods: A total of 179 patients with severe AS were included in this retrospective study. Sarcopenia was determined via CT by measurement of the psoas muscle area (PMA), which was indexed to body surface area (PMAi). According to previous studies, the lowest tertile was defined as sarcopenic. Patients with (59/179) and without sarcopenia (120/179) in the overall cohort were compared by gender-specific cut-offs with regard to the expression of cardiovascular biomarkers such as brain natriuretic peptide (BNP), soluble suppression of tumorigenicity-2 (sST2), growth/differentiation of factor-15 (GDF-15), heart-type fatty-acid binding protein (H-FABP), insulin like growth factor binding protein 2 (IGF-BP2) and soluble urokinase-type plasminogen activator receptor (suPAR). Additionally, binary logistic regression analyses were calculated to detect possible predictors of the presence of sarcopenia. Results: No statistical differences regarding one-year survival could be detected between sarcopenic and non-sarcopenic patients in survival curves (log rank test p = 0.179). In the entire cohort, only BNP and hemoglobin (HB) showed a statistically significant difference, with only HB emerging as a relevant predictor for the presence of sarcopenia after binary logistic regression analysis (p = 0.015). No relevant difference in biomarker expression could be found in the male cohort. Regarding the female cohort, statistically significant differences were found in BNP, HB and hematocrit (HK). In binary logistic regression, however, none of the investigated criteria could be related to sarcopenia. Conclusion: Regardless of gender, patients with imaging-based muscle degradation did not demonstrate significantly different cardiovascular biomarker expression compared to those without it. Full article
(This article belongs to the Special Issue Novel Biomarkers for Acute and Chronic Heart Failure)
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16 pages, 2738 KB  
Article
H-FABP Levels and Psycho-Emotional Improvement of CABG Patients during Cardiac Rehabilitation
by Razan Al Namat, Dina Al Namat, Manuela Ciocoiu, Marius Valeriu Hînganu, Laurențiu Șorodoc, Victorița Șorodoc, Liliana Georgeta Foia, Laura Florea, Cristiana Vlad, Ana Tănasă, Mihai Constantin, Daniel Cioloca, Minerva Codruța Bădescu, Amin Bazyani and Maura Felea
J. Cardiovasc. Dev. Dis. 2022, 9(8), 242; https://doi.org/10.3390/jcdd9080242 - 28 Jul 2022
Cited by 5 | Viewed by 3104
Abstract
(1) Background: The heart-type fatty acid-binding protein (H-FABP) is a specific myocardial biomarker and high levels indicate ischemia regardless of patient-reported symptoms. Concurrently, major adverse cardiovascular events and surgery such as coronary artery by-pass grafting (CABG) cause substantial psycho-emotional distress e.g., depression and [...] Read more.
(1) Background: The heart-type fatty acid-binding protein (H-FABP) is a specific myocardial biomarker and high levels indicate ischemia regardless of patient-reported symptoms. Concurrently, major adverse cardiovascular events and surgery such as coronary artery by-pass grafting (CABG) cause substantial psycho-emotional distress e.g., depression and anxiety. Comprehensive cardiac rehabilitation is, therefore, essential to both physical and psychological recovery. (2) Methods: This is a unicentric, prospective study on 120 consecutive post-CABG patients undergoing a 6-month cardiac rehabilitation program based on physical exercise, Mediterranean diet principles, and Q10 coenzyme antioxidant supplements. H-FABP levels, depression, and anxiety scores (Hamilton HAM-D and HAM-A scales) were monitored after surgery and at 6 months. (3) Results: Mean H-FABP dropped from 60.56 to 4.81. Physical ability increased from 1–2 to 4–5 METS. Mean depression and anxiety improved from 15.88 to 6.96 and from 25.13 to 15.68, respectively. Median scores went down 50% for depression and 9% for anxiety. Explored associations between H-FABP and psycho-emotional status were statistically insignificant. (4) Conclusions: patients adhered to the program and improved significantly in all studied aspects. Clinical significance is discussed in the context of countries like Romania, where such programs are limited by systemic and financial constraints. Further research directions are identified. Full article
(This article belongs to the Topic Biomarkers in Cardiovascular Disease—Chances and Risks)
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