Causal correlations between inflammatory proteins and heart failure: A two‐sample Mendelian randomization analysis DOI Creative Commons
Xian‐Guan Zhu, Geoffrey Liu, Yue Peng

et al.

ESC Heart Failure, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Abstract Aims Inflammation plays a critical role in both the development and progression of heart failure (HF), which is leading cause morbidity mortality worldwide. However, causality between specific inflammation‐related proteins HF risk remains unclear. This study aims to investigate genetically supported inflammatory using two‐sample Mendelian randomization (MR) analysis. Methods results We utilized genome‐wide association (GWAS) data 91 as exposures from SCALLOP Consortium (14,824 participants), alongside outcome GWAS summary statistics FinnGen (29,218 cases/381,838 controls) HERMES (47,309 cases/930,014 for HF, conduct MR For each protein, instrumental variables (IVs) were chosen following three foundational assumptions analysis, requiring minimum qualifying single nucleotide polymorphisms (SNPs) with P < 5e‐8. Associations assessed through inverse‐variance weighted (IVW), MR‐Egger regression, median mode The reliability validity evaluated by examining heterogeneity, horizontal pleiotropy, leave‐one‐out meta‐analysis reverse Heterogeneity refers variation across different genetic variants. Horizontal pleiotropy occurs when variant influences multiple traits biological pathways. Addressing heterogeneity crucial ensuring interpretability results. Our analysis identified associations risk. Matrix metalloproteinase‐1 (MMP‐1) (OR, 1.09; 95% CI, 1.00–1.18; = 0.04) TNF‐beta 1.05; 1.01–1.09; 0.01) positively associated FinnGen. In contrast, urokinase‐type plasminogen activator (uPA) was inversely 0.85; 0.78–0.92; 3.27e‐5) 0.93; 0.87–0.99; 0.03). No evidence observed indicating robustness our findings. A further this association, reduced 0.89; 0.81–0.98; 0.02). found these ( > 0.05 all). Conclusions provides causal positive MMP‐1 suggests their roles disease pathogenesis, whereas inverse uPA indicates its potential protective effect. findings highlight targeting pathways therapeutic strategy HF.

Language: Английский

Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets DOI Creative Commons

Runkai Chen,

Hongrui Zhang,

Botao Tang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 31, 2024

Abstract The immune response holds a pivotal role in cardiovascular disease development. As multifunctional cells of the innate system, macrophages play an essential initial inflammatory that occurs following injury, thereby inducing subsequent damage while also facilitating recovery. Meanwhile, diverse phenotypes and phenotypic alterations strongly associate with distinct types severity diseases, including coronary heart disease, valvular myocarditis, cardiomyopathy, failure, atherosclerosis aneurysm, which underscores importance investigating macrophage regulatory mechanisms within context specific diseases. Besides, recent strides single-cell sequencing technologies have revealed heterogeneity, cell–cell interactions, downstream therapeutic targets at higher resolution, brings new perspectives into macrophage-mediated potential Remarkably, myocardial fibrosis, prevalent characteristic most cardiac remains formidable clinical challenge, necessitating profound investigation impact on fibrosis In this review, we systematically summarize functional plasticity diseases unprecedented insights introduced by technologies, focus different causes characteristics especially relationship between inflammation (myocardial infarction, pressure overload, dilated diabetic cardiomyopathy aging) vascular injury (atherosclerosis aneurysm). Finally, highlight preclinical/clinical targeting strategies translational implications.

Language: Английский

Citations

53
Multiscale drug screening for cardiac fibrosis identifies MD2 as a therapeutic target DOI
Hao Zhang, Phung N. Thai,

Rabindra V. Shivnaraine

et al.

Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

11
Clinical and echocardiographic spectrum of dilated cardiomyopathy: A single-center study DOI Creative Commons

Raj Sachde,

Subhaschandra Gadhvicharan,

Mohit Relwani

et al.

Heart India, Journal Year: 2025, Volume and Issue: 13(1), P. 72 - 75

Published: Jan. 1, 2025

ABSTRACT Background: Dilated cardiomyopathy (DCM) is a leading cause of heart failure, characterized by ventricular dilation and impaired systolic function. This study aims to evaluate clinical echocardiographic features in patients with DCM at single center. Materials Methods: We conducted prospective observational diagnosed our center from December 2023 May 2024. Data collected included demographic information, presentation, parameters (left ejection fraction chamber dimensions). Results: A total 50 higher prevalence male gender (56%) mean age 52.2 years were included. Most (70%) the presented breathlessness orthopnea followed excessive perspiration (60%), bilateral pedal edema (50%), paroxysmal nocturnal dyspnea (40%), palpitations (30%). Echocardiographic findings demonstrated that had lower baseline left fractions (30% ±3.45%) larger end-diastolic diameters (60 ± 4.23 mm), end-systolic diameter (45 3.57 mm) was also increased. Mitral regurgitation (MR) found 80% population; them, 20% severe, 30% moderate, mild MR. The pulmonary artery pressure elevated (30 mmHg). Conclusions: Our concludes mainly middle-aged population clinically presents orthopnea. Echocardiography shows reduced MR majority patients.

Language: Английский

Citations

1
Fibrosis: cross-organ biology and pathways to development of innovative drugs DOI
Florian Rieder, Laura E. Nagy, Toby M. Maher

et al.

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Language: Английский

Citations

1
Integrative transcriptomics and proteomics analysis reveal the protection of Astragaloside IV against myocardial fibrosis by regulating senescence DOI Creative Commons
Lipeng Shi, Jingwei Deng, Jun He

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 975, P. 176632 - 176632

Published: May 6, 2024

Myocardial fibrosis (MF) is a pivotal pathological process implicated in various cardiovascular diseases, particularly heart failure. Astragaloside IV (AS-IV), natural compound derived from Astragalus membranaceus, possesses potent cardioprotective properties. However, the precise molecular mechanisms underlying its anti-MF effects, relation to senescence, remain elusive. Thus, this study aimed investigate therapeutic potential and of AS-IV treating ISO-induced MF mice, employing transcriptomics, proteomics, vitro, vivo experiments. We assessed positive effects on using HE staining, Masson ELISA, immunohistochemical transthoracic echocardiography, transmission electron microscopy, DHE fluorescence staining. Additionally, we elucidated regulatory role through comprehensive transcriptomics proteomics analyses, complemented by Western blotting RT-qPCR validation pertinent pathways. Our findings demonstrated that treatment markedly attenuated myocardial injury oxidative stress, concomitantly inhibiting release SASPs. Furthermore, integrated analyses revealed mechanism was associated with regulating cellular senescence p53 signaling pathway. These results highlight exerts not only stress but also modulating

Language: Английский

Citations

7
Myocardial fibrosis from the perspective of the extracellular matrix: mechanisms to clinical impact DOI
Ida G. Lunde, Karoline Bjarnesdatter Rypdal, Sophie Van Linthout

et al.

Matrix Biology, Journal Year: 2024, Volume and Issue: 134, P. 1 - 22

Published: Aug. 29, 2024

Language: Английский

Citations

7
Myocardial Interstitial Fibrosis in Hypertensive Heart Disease: From Mechanisms to Clinical Management DOI
Arantxa González, Begoña López, Susana Ravassa

et al.

Hypertension, Journal Year: 2023, Volume and Issue: 81(2), P. 218 - 228

Published: Dec. 12, 2023

Hypertensive heart disease (HHD) can no longer be considered as the beneficial adaptive result of hypertrophy cardiomyocytes in response to pressure overload leading development left ventricular hypertrophy. The current evidence indicates that patients with HHD, pathological lesions myocardium lead maladaptive structural remodeling and subsequent alterations cardiac function, electrical activity, perfusion, all contributing poor outcomes. Diffuse myocardial interstitial fibrosis is probably most critically involved lesion these disorders. Therefore, this review, we will focus on histological characteristics, mechanisms, clinical consequences HHD. In addition, consider useful tools for noninvasive diagnosis well effective available therapeutic strategies prevent its or facilitate regression patient population. Finally, issue a call action need more fundamental research

Language: Английский

Citations

16
Heart failure management with β-blockers: can we do better? DOI Creative Commons
Múcio Tavares de Oliveira, Rui Baptista, Sergio Leal

et al.

Current Medical Research and Opinion, Journal Year: 2024, Volume and Issue: 40(sup1), P. 43 - 54

Published: April 1, 2024

Heart failure (HF) is associated with disabling symptoms, poor quality of life, and a prognosis substantial excess mortality in the years following diagnosis. Overactivation sympathetic nervous system key feature pathophysiology HF an important driver process adverse remodelling left ventricular wall that contributes to cardiac failure. Drugs which suppress activity renin-angiotensin-aldosterone system, including β-blockers, are foundation therapies for management heart reduced ejection fraction (HFrEF) despite lack specific outcomes trials, also widely used by cardiologist patients preserved (HFpEF). Today, expert opinion has moved away from recommending treatment should be guided solely LVEF interventions rather address signs symptoms (e.g. oedema tachycardia), severity HF, concomitant conditions. β-blockers improve functional status these agents have demonstrated improved survival, as well risk other clinical such hospitalisation failure, randomised, placebo-controlled trials. In HFpEF, anti-ischemic lower blood pressure rate. Moreover, reduce setting occurring alongside common comorbid conditions, diabetes, CKD (of any severity), COPD. Higher doses better populations so ensuring adequate titration therapy their maximal (or maximally tolerated) optimal people HF. principle, patient could combined β-blocker, inhibitor/neprilysin inhibitor, mineralocorticoid receptor antagonist, SGLT2 according tolerability.

Language: Английский

Citations

5
m6A control programmed cell death in cardiac fibrosis DOI
Zhenyu Liu,

Qing-Ye You,

Zhiyan Liu

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 353, P. 122922 - 122922

Published: July 18, 2024

Language: Английский

Citations

5
Elevated Septal Native T1 Time in CMR Imaging Suggesting Myocardial Fibrosis in Young Kidney Transplant Recipients DOI Creative Commons

Tim Alexander Ubenauf,

Jeannine von der Born,

Rizky I. Sugianto

et al.

Journal of Cardiovascular Magnetic Resonance, Journal Year: 2025, Volume and Issue: unknown, P. 101839 - 101839

Published: Jan. 1, 2025

Patients after kidney transplantation (KTx) in childhood show a high prevalence of cardiac complications, but the underlying mechanism is still poorly understood. In adults, myocardial fibrosis detected magnetic resonance (CMR) imaging already an established risk factor. Data for children KTx are not available. This study aimed to explore function and structure with focus on associated factors recipients. 46 recipients (mean age 16.0 ± 3.5 years) age- sex-matched healthy controls were examined non-contrast CMR imaging. Native T1 time (nT1), marker fibrosis, was measured at interventricular septum. Other parameters comprised left ventricular mass index (LVMI), ejection fraction (LVEF), global longitudinal strain (GLS). Multivariable linear regression analyses used associations nT1. Mean nT1 significantly higher than (1198.1±48.8ms vs. 1154.4±23.4ms, p<0.0001). Twenty-one (46%) had above upper limit normal range + 2SD controls). showed LVMI z-scores (0.1±1.1 -0.3±0.7, p=0.026), LVEF (67.3±3.8% 65.3±3.6%, p=0.012), lower GLS (-19.0±2.1% -20.3±2.7%, p=0.010). Higher systolic blood pressure (SBP; ß=1.284, p=0.001), (ß=1.542, p<0.001), (ß=3.535, p=0.026) longer only recipients, controls. Only two exhibited hypertrophy, however, total 18 displayed elevated z-score within range. Our data suggest presence remodeling significant proportion young Non-contrast has potential visualize early structural changes could become important diagnostic adjunct follow-up Longitudinal studies needed further evaluate importance identification those sudden death allowing integrate preventive strategies.

Language: Английский

Citations

0