Biomedicines

Research

21 pages, 32423 KB

Open AccessArticle

KuJiang GanLuoYin Alleviates Hypertensive Vascular Injury and Modulates FMO2/FTO/m⁶A Signaling

by Tong Sun, Jianghong Li, Ruijie Shi, Haitao Xie, Siyuan Yin, Xueqian Liu, Shi Wang, Jiandong Chen, Shuhua Tang and Xiaohu Chen

Biomedicines 2026, 14(7), 1469; https://doi.org/10.3390/biomedicines14071469 - 28 Jun 2026

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Abstract

Background: Hypertension-induced vascular injury involves endothelial dysfunction, inflammation, and oxidative stress, leading to vascular remodeling and cardiovascular complications. Flavin-containing monooxygenase 2 (FMO2) has been implicated in redox regulation, but its role in hypertensive vascular injury remains unclear. This study investigated whether KuJiang [...] Read more.

Background: Hypertension-induced vascular injury involves endothelial dysfunction, inflammation, and oxidative stress, leading to vascular remodeling and cardiovascular complications. Flavin-containing monooxygenase 2 (FMO2) has been implicated in redox regulation, but its role in hypertensive vascular injury remains unclear. This study investigated whether KuJiang GanLuoYin (KJGLY) protects against hypertensive vascular injury and whether FMO2-associated Fat mass and obesity-associated protein (FTO)/N6-methyladenosine (m⁶A) signaling is involved. Methods: Spontaneously hypertensive rats (SHRs) were treated with KJGLY for eight weeks. Blood pressure, vascular remodeling, inflammation, oxidative stress, and global m⁶A RNA methylation were assessed. Integrated metabolomic and proteomic analyses were performed to identify treatment-associated molecular alterations and candidate proteins. AAV9-mediated FMO2 knockdown in SHRs and gain- and loss-of-function approaches in angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells were used to examine the functional involvement of FMO2. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based chemical profiling and High-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) quantification were performed to characterize the major constituents of KJGLY. Results: KJGLY significantly reduced blood pressure and alleviated vascular remodeling in SHRs. Metabolomic and proteomic analyses revealed treatment-associated alterations in inflammatory and lipid metabolic pathways and identified FMO2 as a treatment-responsive candidate. KJGLY restored FMO2 expression, reduced FTO abundance and NF-κB activation, increased global m⁶A levels, and attenuated inflammatory and oxidative stress responses in hypertensive aortas. Conversely, AAV9-mediated FMO2 knockdown aggravated vascular injury, enhanced inflammation and oxidative stress, reduced global m⁶A levels, and increased NF-κB activation. Co-immunoprecipitation showed an association between FMO2 and FTO, and MeRIP-qPCR indicated that FMO2 manipulation altered m⁶A enrichment of VCAM-1 mRNA. In Ang II-stimulated endothelial cells, linarin, the most abundant quantified constituent of KJGLY, partially recapitulated the cellular effects of KJGLY, including restoration of FMO2/FTO-associated signaling and attenuation of inflammatory activation. Conclusions: These findings support a functional role for FMO2 in hypertensive vascular injury and suggest that FMO2-associated modulation of FTO/m⁶A signaling may contribute to the vascular protective effects of KJGLY. Linarin recapitulated key protective effects in vitro, although its in vivo contribution to the formula remains to be determined. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases: Pathophysiological Insights, Therapeutic Strategies and Future Directions)

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22 pages, 3682 KB

Open AccessArticle

Molecular Hydrogen Modulates the Baroreflex Activity and Reduces the Vascular Adrenoreceptor Sensitivity to Phenylephrine and Lung Inflammation in Rats with Pulmonary Hypertension

by Marina Artemieva, Larisa Kozaeva, Tatyana Kuropatkina, Khaidar Gufranov, Dmitrii Atiakshin, Natalia Medvedeva and Oleg Medvedev

Biomedicines 2026, 14(3), 494; https://doi.org/10.3390/biomedicines14030494 - 24 Feb 2026

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Abstract

Background/Objectives: Molecular hydrogen (H₂), a natural antioxidant, can selectively reduce hydroxyl radicals and peroxynitrite without affecting signaling molecules such as H₂O₂ and NO. In addition, H₂ can inhibit the synthesis of inflammatory cytokines. Human and animal studies [...] Read more.

Background/Objectives: Molecular hydrogen (H₂), a natural antioxidant, can selectively reduce hydroxyl radicals and peroxynitrite without affecting signaling molecules such as H₂O₂ and NO. In addition, H₂ can inhibit the synthesis of inflammatory cytokines. Human and animal studies have shown that the inhalation of H₂ has a hypotensive effect. In this context, the aim of the present work was to study the effect of H₂ on the baroreflex regulation of blood pressure in rats with experimental monocrotaline-induced pulmonary hypertension (MCT) in vivo and the effects of H₂ on the reactivity of isolated rat aorta with MCT pulmonary hypertension to α₁-adrenoceptor agonists in vitro. Methods: Experiments were performed on male Wistar rats with MCT pulmonary hypertension; animals were placed in plastic chambers aerated with atmospheric air at a rate of 4 L/min with O₂ and CO₂ control. Cages with the rats of the MCT-H₂ and Control-H₂ groups were ventilated with air containing 4% H₂ twice daily for 2 h each. The MCT-Air and Control-Air groups breathed only atmospheric air. The duration of the experiment was 21 days. On day 20, blood pressure and heart rate (HR) were measured in awake animals and the baroreflex response to phenylephrine (PE) and nitroprusside (NP) was tested. In in vitro experiments, we studied the effect of adding H₂ to the perfusion solution on the responsiveness of isolated aortic preparations from MCT and control rats to the α₁-adrenoceptor agonist PE and the vasodilators NP and Acetylcholine. Results: When the effect of H₂ on the baroreflex response to NP (4.5 μg/kg) was examined in awake rats, the increase in HR was 73.1 ± 16.7 beats/min in the MCT-Air group and 48.1 ± 10.2 beats/min in the MCT-H₂ group (p < 0.01). In the Control-H₂ and Control-Air groups, there was a trend towards a lower HR in the Control-H₂ group, but the differences were not significant. No differences in HR response to PE administration were found between any of the experimental groups. Experiments on isolated aortic preparations from MCT rats showed that the addition of H₂ to the perfusion medium resulted in a 30% reduction in the maximal response to PE compared with the MCT group without hydrogen (p < 0.01), and the potency of PE (EC₅₀) decreased threefold (p < 0.05). There was a decrease in tryptase secretion, indicating an anti-inflammatory effect of H₂. Conclusions. The results demonstrate that H₂ inhalation was associated with an attenuated heart rate response to nitroprusside-induced hypotension and reduced vascular reactivity to phenylephrine in rats with pulmonary hypertension. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases: Pathophysiological Insights, Therapeutic Strategies and Future Directions)

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10 pages, 1646 KB

Open AccessArticle

Aortic Valve Annular Properties in Cardiac Amyloidosis—Insights from the Three-Dimensional Speckle Tracking Echocardiographic MAGYAR-Path Study

by Attila Nemes, Nóra Ambrus and Zita Borbényi

Biomedicines 2026, 14(2), 488; https://doi.org/10.3390/biomedicines14020488 - 23 Feb 2026

Cited by 1 | Viewed by 576

Abstract

Introduction. The etiology of cardiac amyloidosis (CA) involves the systemic or localized deposition of misfolded amyloid proteins within the myocardial interstitium and valvular structures. The primary objective of this study was to employ three-dimensional speckle-tracking echocardiography (3DSTE) to perform a detailed analysis of [...] Read more.

Introduction. The etiology of cardiac amyloidosis (CA) involves the systemic or localized deposition of misfolded amyloid proteins within the myocardial interstitium and valvular structures. The primary objective of this study was to employ three-dimensional speckle-tracking echocardiography (3DSTE) to perform a detailed analysis of the aortic valve annulus (AVA) and left ventricular (LV) strains in CA patients and to compare these parameters with those of matched healthy controls. Methods. The initial cohort for this study comprised 35 individuals diagnosed with CA. However, 12 patients were subsequently excluded from the final analysis due to suboptimal image quality precluding accurate measurement of AVA dimensions and/or LV strains. The final analytical group, therefore, consisted of 23 CA patients (14 males), with a mean age of 64.6 ± 7.1 years. The results obtained from the CA patient group were compared with those of a healthy control cohort comprising 23 individuals (14 males; mean age: 53.2 ± 5.3 years). Results. In CA patients, AVA area was greater in end-diastole in 11 out of 23 cases (48%), and in end-systole in 8 out of 23 cases (35%), while it proved to be equal in 4 out of 23 cases (17%). The ratio of healthy controls with greater end-diastolic AVA area (12 out of 23, 52%) and greater end-systolic AVA area (11 out of 23, 48%) did not differ from that of CA patients. End-diastolic and end-systolic maximum and minimum AVA diameters, areas and perimeters did not differ between CA patients and matched controls. AVA plane systolic excursion (AAPSE) was found to be significantly impaired in all CA patients irrespective of AVA area size. Basal LV radial (RS), circumferential (CS) and longitudinal (LS) strains were reduced in CA patients compared with those of controls. End-systolic AVA dimensions tended to be reduced in CA patients with greater end-diastolic AVA area compared with those with greater end-systolic AVA area. While basal LV-RS and LV-CS proved to be similar between CA subgroups, basal LV-LS tended to be higher in CA patients with greater end-systolic AVA area. Controls with greater end-diastolic AVA area showed lower basal LV-RS and LV-LS compared with those with greater end-systolic AVA area. CA patients with equal end-diastolic and end-systolic AVA area (n = 4) showed similarly reduced AAPSE, basal LV-RS, basal LV-CS and LV-LS. Conclusions. In the presence of CA, the AVA is not dilated; however, its spatial displacement is reduced, suggesting its functional impairment, as represented by AAPSE, possibly due to the reduction in all concomitant LV strain parameters. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases: Pathophysiological Insights, Therapeutic Strategies and Future Directions)

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13 pages, 1556 KB

Open AccessArticle

The Complexity of the Relationship Between Mitral and Aortic Valve Annular Dimensions in the Same Healthy Adults: Detailed Insights from the Three-Dimensional Speckle-Tracking Echocardiographic MAGYAR-Healthy Study

by Attila Nemes, Barbara Bordács, Nóra Ambrus and Csaba Lengyel

Biomedicines 2026, 14(2), 304; https://doi.org/10.3390/biomedicines14020304 - 29 Jan 2026

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Abstract

Introduction. Although the aortic valve and mitral valve differ significantly in structure, function, and location, they both play a significant role in left ventricular (LV) function. The aim of the current study was to analyze the relationship between the mitral valve annulus (MVA) [...] Read more.

Introduction. Although the aortic valve and mitral valve differ significantly in structure, function, and location, they both play a significant role in left ventricular (LV) function. The aim of the current study was to analyze the relationship between the mitral valve annulus (MVA) and the aortic valve annulus (AVA), as measured by three-dimensional speckle-tracking echocardiography (3DSTE) in the same healthy individuals with average or smaller/larger annular diameters (Ds), areas (As), and perimeters (Ps) in end-diastole (D) and end-systole (S). Methods. This study comprised 134 healthy adult participants with a mean age of 31.0 (16.0) years (73 males). A complete medical investigation included physical examination, laboratory tests, standard 12-lead electrocardiography, and two-dimensional Doppler echocardiography supplemented with 3DSTE. Results. Almost all end-diastolic and end-systolic MVA dimensions increased significantly with enlarging MVA. Similarly, as MVA-D-D and MVA-P-D increased, nearly all end-diastolic and end-systolic AVA dimensions exhibited a positive trend. Lower-than-average MVA-A-D was associated with a trend toward higher AVA dimensions (excluding AVA-P-D) compared to the mean MVA-A-D; conversely, higher-than-average MVA-A-D was also associated with increased AVA dimensions. AVA perimeter values were notably higher than those recorded in the lower-than-average MVA-A-D subgroup. In subjects with lower-than-average end-diastolic MVA dimensions, a non-significantly higher proportion of larger end-systolic AVA was observed relative to end-diastolic AVA. While AVA dimensions remained unchanged despite increasing MVA-D-S, a positive trend in AVA dimensions—reaching statistical significance for certain parameters—was observed alongside increasing MVA-A-S and MVA-P-S. In subjects with lower-than-average end-systolic MVA dimensions, there was a non-significantly higher prevalence of larger end-systolic AVA compared to end-diastolic AVA. Furthermore, nearly all end-diastolic and end-systolic AVA dimensions increased significantly with increasing AVA. Increases in AVA-D-D, AVA-A-D, and AVA-P-D were generally accompanied by a trend toward higher end-diastolic and end-systolic MVA dimensions; however, MVA-D-S peaked in the presence of lower-than-average end-diastolic AVA dimensions. In subjects with lower-than-average end-diastolic AVA, a non-significantly higher proportion of larger end-systolic AVA was noted compared to end-diastolic AVA. Notably higher MVA parameters were observed in the presence of mean AVA-D-S and AVA-A-S compared to their lower-than-average counterparts. Finally, end-diastolic MVA parameters showed a positive trend with increasing AVA-P-S, and subjects with higher-than-average end-systolic AVA dimensions demonstrated a significantly higher proportion of larger end-systolic AVA compared to end-diastolic AVA. Conclusions. There is a strong and complex association between the dimensions of the MVA and AVA, as assessed by 3DSTE, when measured simultaneously in the same healthy adults. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases: Pathophysiological Insights, Therapeutic Strategies and Future Directions)

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30 pages, 3778 KB

Open AccessArticle

Polypharmacy and Drug–Drug Interaction Architecture in Hospitalized Cardiovascular Patients: Insights from Real-World Analysis

by Andrei-Flavius Radu, Ada Radu, Gabriela S. Bungau, Delia Mirela Tit, Cosmin Mihai Vesa, Tunde Jurca, Diana Uivarosan, Daniela Gitea, Roxana Brata and Cristiana Bustea

Biomedicines 2026, 14(1), 218; https://doi.org/10.3390/biomedicines14010218 - 20 Jan 2026

Cited by 3 | Viewed by 1941

Abstract

Background: Cardiovascular polypharmacy inherently amplifies the risk of drug–drug interactions (DDIs), yet most studies remain limited to isolated drug pairs or predefined high-risk classes, without mapping the systemic architecture through which interactions accumulate. Objectives: To characterize the burden, severity, and network structure of [...] Read more.

Background: Cardiovascular polypharmacy inherently amplifies the risk of drug–drug interactions (DDIs), yet most studies remain limited to isolated drug pairs or predefined high-risk classes, without mapping the systemic architecture through which interactions accumulate. Objectives: To characterize the burden, severity, and network structure of potential DDIs in a real-world cohort of hospitalized cardiovascular patients using interaction profiling combined with graph-theoretic network analysis. Methods: This retrospective observational study included 250 hospitalized cardiovascular patients. All home medications at admission were analyzed using the Drugs.com interaction database, and a drug interaction network was constructed to compute topological metrics (i.e., degree, betweenness, and eigenvector centrality). Results: Polypharmacy was highly prevalent, with a mean of 7.7 drugs per patient, and 98.4% of patients exhibited at least one potential DDI. A total of 4353 interactions were identified, of which 12.1% were classified as major, and 35.2% of patients presented high-risk profiles with ≥3 major interactions. Interaction burden showed a strong correlation with medication count (r = 0.929). Network analysis revealed a limited cluster of hub medications, particularly pantoprazole, furosemide, spironolactone, amiodarone, and perindopril, that disproportionately governed both interaction density and high-severity risk. Conclusions: These findings move beyond conventional pairwise screening by demonstrating how interaction risk propagates through interconnected therapeutic networks. The study supports the integration of hub-focused deprescribing, targeted monitoring strategies, and network-informed clinical decision support to mitigate DDI risk in cardiovascular polypharmacy. Future studies should link potential DDIs to clinical outcomes and validate network-based prediction models in prospective settings. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases: Pathophysiological Insights, Therapeutic Strategies and Future Directions)

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12 pages, 850 KB

Open AccessArticle

Circulating miR-223-3p as an Independent Biomarker of Recurrent Thrombotic Risk After Ischemic Stroke

by Bence Balczó, Katalin Maricza, Krisztina Molnár, Zsuzsanna Elek, Zsófia Bánlaki, Réka Kovács-Nagy, Gergely Keszler, Zsolt Rónai, Abigél Molnár and Tihamér Molnár

Biomedicines 2025, 13(12), 2961; https://doi.org/10.3390/biomedicines13122961 - 1 Dec 2025

Cited by 1 | Viewed by 894

Abstract

Background: Circulating microRNAs (miRNAs) have emerged as potential biomarkers of platelet reactivity and thrombotic risk. Among them, miR-223-3p regulates P2Y12 receptor expression and may influence response to antiplatelet therapy. This study aimed to evaluate the prognostic value of selected circulating miRNAs in post-stroke [...] Read more.

Background: Circulating microRNAs (miRNAs) have emerged as potential biomarkers of platelet reactivity and thrombotic risk. Among them, miR-223-3p regulates P2Y12 receptor expression and may influence response to antiplatelet therapy. This study aimed to evaluate the prognostic value of selected circulating miRNAs in post-stroke patients receiving antiplatelet treatment. Methods: Sixty ischemic stroke survivors were prospectively enrolled and followed for 18 months for recurrent vascular events (stroke, transient ischemic attack, or myocardial infarction). Plasma levels of miR-126-3p, miR-223-3p, miR-24-3p, and miR-199a-5p were quantified using reverse transcription real-time PCR. Clinical data, antiplatelet regimen, statin use, and Essen Stroke Risk Scores (ESRS) were recorded. Logistic regression was applied to identify independent predictors of thrombotic events. Results: Expression of all examined miRNAs differed significantly across treatment groups. The dual antiplatelet therapy (DAPT) group showed the highest levels of miR-126-3p and miR-199a-5p (p < 0.01). Within the statin-naïve DAPT subgroup, lower miR-199a-5p levels (p < 0.001) were observed among patients who experienced ischemic events (n = 7/60; 12%; stroke = 4, TIA = 2, ACS = 1) during 18 months of follow-up. In multivariate analysis, reduced miR-223-3p remained the only independent predictor of recurrent thrombotic events (OR 1.18, 95% CI 1.01–1.37, p = 0.036), independent of ESRS and platelet reactivity. Elevated miR-126-3p and miR-199a-5p were associated with favorable treatment response, particularly among statin users. Conclusions: This study identifies low circulating miR-223-3p as an independent biomarker of thrombotic risk in post-stroke patients, potentially reflecting enhanced platelet activation via P2Y12 signaling. In contrast, higher miR-126-3p and miR-199a-5p levels may indicate more effective antiplatelet response. These findings support the potential utility of miRNA profiling for individualized antiplatelet therapy and long-term risk stratification after ischemic stroke. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases: Pathophysiological Insights, Therapeutic Strategies and Future Directions)

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16 pages, 3920 KB

Open AccessArticle

17βH-Neriifolin Improves Cardiac Remodeling Through Modulation of Calcium Handling Proteins in the Heart Failure Rat Model

by Rajasegar Anamalley, Yusof Kamisah, Nurhanan Murni Yunos and Satirah Zainalabidin

Biomedicines 2025, 13(9), 2115; https://doi.org/10.3390/biomedicines13092115 - 29 Aug 2025

Cited by 1 | Viewed by 1690

Abstract

Background: Cardiac glycosides such as digoxin have been commonly used for patients with heart failure; however, their toxicity remains a main concern. 17βH-neriifolin (SNA209), a cardiac glycoside compound, has been recently isolated from Ceberra odollum Gaertn and was shown to improve the [...] Read more.

Background: Cardiac glycosides such as digoxin have been commonly used for patients with heart failure; however, their toxicity remains a main concern. 17βH-neriifolin (SNA209), a cardiac glycoside compound, has been recently isolated from Ceberra odollum Gaertn and was shown to improve the heart’s pumping ability in failing hearts ex vivo. Thus, this study aimed to investigate the potential use of SNA209 as a treatment for isoprenaline (ISO)-induced heart failure in rats. Methods: Forty male Wistar rats were randomly divided into five groups. Heart failure was induced by isoprenaline (ISO, 10 mg/kg/s.c) for 14 days daily, followed by SNA209 treatment (5 mg/kg; p.o) for another 14 days daily. Control rats were given saline as a vehicle for ISO and DMSO as a vehicle for SNA209. Results: Systolic and diastolic blood pressure (SBP and DBP) in all ISO-treated groups were significantly increased compared to the control group (p < 0.05), and SNA209 treatment managed to reduce the SBP and DBP. Additionally, SNA209 treatment significantly increased the heart rate and normalized the ECG parameters in ISO-treated rats. Pro-B-type natriuretic peptide and troponin T level, a cardiac injury markers, was remarkably reduced by SNA209 in the ISO-treated group. Cardiac hypertrophy was evident in increased cardiomyocyte size in ISO groups; however, SNA reduced the cardiomyocyte size. The left ventricular developed pressure (LVDP) in ISO treated with SNA209 was significantly raised, indicating a chronotropic effect. Cardiac Na⁺/K⁺-ATPase expression of the α1 subunit, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2a (SERCA2a), and sodium–calcium exchanger subunit were significantly increased in the SNA treatment groups. Conclusions: The SNA 209 treatment improved cardiac function and structure, likely via modulating intracellular calcium management, so underscoring its potential as an adjuvant therapy for heart failure. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases: Pathophysiological Insights, Therapeutic Strategies and Future Directions)

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20 pages, 3967 KB

Open AccessArticle

Targeting the Opioid System in Cardiovascular Disease: Liver Proteomic and Lipid Profile Effects of Naloxone in Atherosclerosis

by Kinga Jaskuła, Agata Nawrocka, Piotr Poznański, Aneta Stachowicz, Marzena Łazarczyk, Mariusz Sacharczuk, Zbigniew Gaciong and Dominik S. Skiba

Biomedicines 2025, 13(8), 1802; https://doi.org/10.3390/biomedicines13081802 - 23 Jul 2025

Cited by 1 | Viewed by 1382

Abstract

Background: The endogenous opioid system plays a pivotal role in numerous physiological processes and is implicated in a range of diseases, including atherosclerosis, a condition contributing to nearly 50% of deaths in Western societies. Objectives: This study investigates the effects of opioid receptor [...] Read more.

Background: The endogenous opioid system plays a pivotal role in numerous physiological processes and is implicated in a range of diseases, including atherosclerosis, a condition contributing to nearly 50% of deaths in Western societies. Objectives: This study investigates the effects of opioid receptor blockade, using naloxone, on the plasma lipid profile and atherosclerosis progression. Methods: ApoE^−/− mice with advanced atherosclerosis were treated with naloxone for seven days, and the effects on atherosclerotic plaque development and liver steatosis were evaluated. Results: A proteomic analysis of liver samples post-treatment identified 38 proteins with altered abundance. The results revealed that naloxone treatment led to an increase in HDL cholesterol, a lipid fraction associated with protective cardiovascular effects. Furthermore, naloxone did not influence the progression of atherosclerotic plaques or the development of liver steatosis. Conclusions: In conclusion, while short-term naloxone treatment in mice with advanced atherosclerosis does not alter overall atherosclerotic plaque progression or liver steatosis, the observed elevation in HDL cholesterol and the extensive changes in liver protein abundance underscore the complex and multifaceted role of the opioid system in lipid metabolism and cardiovascular health. These findings provide a foundation for further exploration of opioid receptor antagonists as modulators of lipid profiles and potential contributors to cardiovascular therapy. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases: Pathophysiological Insights, Therapeutic Strategies and Future Directions)

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Review

Jump to: Research, Other

13 pages, 1214 KB

Open AccessReview

Adipose Tissue, Natriuretic Peptides, and HFpEF: Clinical Implications of the Obesity Paradox

by Michał Maksymilian Wilk and Piotr Gajewski

Biomedicines 2026, 14(6), 1305; https://doi.org/10.3390/biomedicines14061305 - 9 Jun 2026

Viewed by 506

Abstract

Introduction: Adipose tissue (AT) is increasingly recognized as an active endocrine and immunological organ involved in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Dysfunctional AT, particularly visceral, promotes chronic low-grade inflammation, endothelial dysfunction, and microvascular damage. At the same [...] Read more.

Introduction: Adipose tissue (AT) is increasingly recognized as an active endocrine and immunological organ involved in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Dysfunctional AT, particularly visceral, promotes chronic low-grade inflammation, endothelial dysfunction, and microvascular damage. At the same time, higher body mass is associated with paradoxically lower natriuretic peptide (NP) levels, which may impact diagnostic accuracy in HFpEF. Methods: This narrative review summarizes the current evidence on the interplay between adipose tissue, NPs, and HFpEF, focusing on pathophysiological mechanisms, AT distribution, and clinical implications. Results: Adipokine-mediated inflammation contributes to the myocardial stiffness, fibrosis, and cardiac remodeling characteristic of HFpEF. Visceral adipose tissue, including epicardial fat, exhibits a more proinflammatory profile than subcutaneous fat. Obesity is associated with decreased NP levels due to increased clearance and decreased production. Consequently, lower NP levels may lead to underdiagnosis or misclassification of HFpEF, particularly in diagnostic algorithms such as HFA-PEFF and H₂FPEF. Patients with low BMI or cachexia exhibit elevated NP levels, reflecting advanced disease and catabolic states. Conclusions: The obesity-natriuretic paradox poses a key diagnostic challenge in HFpEF. Interpretation of natriuretic peptide levels should take body composition into account, and refinement of biomarker cutoff values may improve diagnostic accuracy. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases: Pathophysiological Insights, Therapeutic Strategies and Future Directions)

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33 pages, 1280 KB

Open AccessReview

Multi-Omics and Artificial Intelligence in Cardiovascular Medicine: From Mechanistic Insights to Clinical Translation

by Ewelina Młynarska, Kinga Bojdo, Oliwia Mazur, Kacper Pawlak, Aleksandra Przybylak, Natalia Kustosik, Katarzyna Krawiranda, Jacek Rysz and Beata Franczyk

Biomedicines 2026, 14(6), 1301; https://doi.org/10.3390/biomedicines14061301 - 8 Jun 2026

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Abstract

Background: Cardiovascular diseases (CVDs) remain the leading global cause of mortality, yet a critical “translational gap” persists: Conventional biomarkers often fail to detect subclinical stages or predict individual disease trajectories. While single-omics studies have proliferated, the field lacks a unified framework synthesizing these [...] Read more.

Background: Cardiovascular diseases (CVDs) remain the leading global cause of mortality, yet a critical “translational gap” persists: Conventional biomarkers often fail to detect subclinical stages or predict individual disease trajectories. While single-omics studies have proliferated, the field lacks a unified framework synthesizing these molecular layers with advanced computational intelligence. Aim: This review addresses this gap by evaluating the synergistic integration of multi-omics and Artificial Intelligence (AI) to transition from descriptive markers toward predictive precision cardiology. Scope: Evidence from non-coding RNA networks (miRNAs, lncRNAs) and exosomal trafficking is synthesized alongside a critical assessment of Machine Learning (ML) architectures, including supervised, unsupervised, and deep learning (DL) models. Findings: Unlike traditional reviews, this work delineates the specific pipelines required to deconvolute high-dimensional signatures—such as TMAO, acylcarnitines, and cardiac-enriched miRNAs—into actionable risk models for heart failure (HF) and post-infarction outcomes. The primary barrier to clinical translation is identified not as data scarcity but as the lack of standardized bioinformatic workflows and model interpretability. Conclusions: This review distinguishes itself by proposing an integrated molecular–computational framework that prioritizes Explainable AI (XAI) and standardized multi-omic protocols. Such a shift is essential to bridge the gap between high-dimensional biological insights and routine clinical decision-making. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases: Pathophysiological Insights, Therapeutic Strategies and Future Directions)

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Other

Jump to: Research, Review

19 pages, 688 KB

Open AccessSystematic Review

A Systematic Review of Literature on the Association Among Sleep, Cortisol Level and Cardiovascular Health Within the Healthcare Shift Worker Population

by Aslah Nabilah Abdull Sukor, Norsham Juliana, Nazefah Abdul Hamid, Nur Islami Mohd Fahmi Teng, Muslimah Ithnin, Sahar Azmani and Sazzli Shahlan Kasim

Biomedicines 2025, 13(10), 2539; https://doi.org/10.3390/biomedicines13102539 - 17 Oct 2025

Cited by 6 | Viewed by 8392

Abstract

Shift workers are commonly associated with circadian misalignment due to irregular working hours, which often leads to poor sleep quality and is associated with HPA axis misalignment and changes in cardiovascular outcome. Background: This systematic review aimed to investigate the association between cortisol [...] Read more.

Shift workers are commonly associated with circadian misalignment due to irregular working hours, which often leads to poor sleep quality and is associated with HPA axis misalignment and changes in cardiovascular outcome. Background: This systematic review aimed to investigate the association between cortisol production and cardiovascular health with sleep quality in healthcare shift workers. Methods: A comprehensive search of PubMed, Web of Science, and Scopus was conducted for studies published between 2010 and 2025, according to PRISMA guidelines. Fourteen studies met the inclusion criteria. Results: Among the included studies, eight studies focused on the relationship between sleep quality and cortisol regulation, five studies investigated the link between sleep quality and cardiovascular health, and one study examined sleep quality, cortisol regulation, and cardiovascular outcome. A significant relationship between cortisol and sleep quality was observed, as lower cortisol levels upon awakening were associated with low sleep quality. Several studies reported that sleep disturbances were associated with adverse cardiovascular outcomes, including reduced heart rate variability (HRV) and increased risk of metabolic syndrome. Conclusions: This review highlights existing literature on the critical role of sleep quality as a key factor in cortisol level and cardiovascular health in shift workers, along with the factors influencing circadian rhythm. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases: Pathophysiological Insights, Therapeutic Strategies and Future Directions)

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14 pages, 1020 KB

Open AccessSystematic Review

The Effects of High-Fat Diet on the Molecular Pathways in Cardiac Tissue: A Systematic Review of In Vivo Rodent Studies and Integrated Bioinformatic Analysis

by Muhammad Syaffuan Ahmad Najib, Marjanu Hikmah Elias, Norsham Juliana, Siti Hamimah Sheikh Abdul Kadir, Effendi Ibrahim and Nazefah Abdul Hamid

Biomedicines 2025, 13(9), 2071; https://doi.org/10.3390/biomedicines13092071 - 26 Aug 2025

Cited by 1 | Viewed by 1941

Abstract

Background/Objectives: The global high prevalence of cardiovascular diseases (CVDs) is attributed to the high prevalence of obesity and metabolic syndrome. However, the impact of a high-fat diet (HFD) on the expression of genes in cardiac tissue remains poorly understood. Methods: A thorough literature [...] Read more.

Background/Objectives: The global high prevalence of cardiovascular diseases (CVDs) is attributed to the high prevalence of obesity and metabolic syndrome. However, the impact of a high-fat diet (HFD) on the expression of genes in cardiac tissue remains poorly understood. Methods: A thorough literature search was performed using PubMed, Scopus, EBSCOhost, and ScienceDirect databases. The Medical Subject Heading (MeSH) terms such as “high-fat diet”, “gene expression” and “cardiac tissue” were used as the keywords in all fields. Results: A total of 1608 studies were retrieved, and only in vivo experimental studies to identify cardiac tissues differentially expressed genes (DEGs) or proteins (DEPs) in rodents fed with HFD were selected. After screening, 14 studies were selected, 159 DEGs and DEPs were extracted from the data and further analysis was conducted employing DAVID, STRING, and Cytoscape 3.10.3 software. A protein–protein interaction (PPI) network revealed a total of 159 genes and proteins from the selected DEGs containing 100 nodes and 292 edges with a PPI enrichment p-value of < 1.0 × 10⁻¹⁶ and an average local clustering coefficient of 0.447 with an average node degree of 5.84. Six significant clusters with high intermolecular interactions from the protein–protein interaction (PPI) network complex reveal significant molecular pathways, including the glucose metabolic process, fatty acid metabolic process, and inflammatory response (p < 0.05). Conclusions: The identification of the critical link between obesity and HFD-induced CVDs in cardiac tissue highlights the need for a deeper understanding of the molecular mechanisms controlling gene expression in cardiac tissue. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Diseases: Pathophysiological Insights, Therapeutic Strategies and Future Directions)

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