OPA1 mediates cardiac function and metabolism: in silico and in vivo evidence DOI Creative Commons
Claire Fong-McMaster,

Serena M. Pulente,

Luke Kennedy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 24, 2024

Abstract OPA1 is an inner mitochondrial membrane protein that mediates diverse signaling processes. important for cardiac function and protects against insults such as ischemia reperfusion injury. We sought to further assess in human mouse pathologies, hypothesizing may also a protective manner chronic heart failure. Bioinformatic analyses of histological transcript data from the GTEx database indicated expression levels vary heart, where elevated were correlated with fatty acid, branch chain amino acid contractile gene signatures. To experimentally these correlations, mice 1.5-fold whole body overexpression (OPA1-OE) subjected transverse aortic constriction surgery displayed improved 2D 4D functional parameters compared WT mice. OPA1-OE had no induction fibrotic markers sustained markers. Maximal oxidative capacity was both myofibers post-TAC. These results demonstrate role mediating highlight pathways.

Language: Английский

Nuclear receptor subfamily 4 group A member 1 promotes myocardial ischemia/reperfusion injury through inducing mitochondrial fission factor-mediated mitochondrial fragmentation and inhibiting FUN14 domain containing 1-depedent mitophagy DOI Creative Commons
Junyan Wang,

Haowen Zhuang,

Lianqun Jia

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(11), P. 4458 - 4475

Published: Jan. 1, 2024

This study investigated the mechanism by which NR4A1 regulates mitochondrial fission factor (Mff)-related and FUN14 domain 1 (FUNDC1)-mediated mitophagy following cardiac ischemia-reperfusion injury(I/R). Our findings showed that damage regulation was positively correlated with pathological pan-apoptosis of myocardial cell mitochondria. Compared wild-type mice (WT), NR4A1-knockout exhibited resistance to injury fission, characterized activation. Results increased expression level, activating mediated Mff restoring phenotype FUNDC1. The inactivation FUNDC1 phosphorylation could not mediate normalization in a timely manner, leading an excessive stress response unfolded proteins imbalance homeostasis. process disrupted quality control network, accumulation damaged mitochondria activation pan-apoptotic programs. data indicate is novel critical target I/R exertsand negative regulatory effects Mff-mediated mito-fission inhibiting FUNDC1-mediated mitophagy. Targeting crosstalk balance between NR4A1-Mff-FUNDC1 potential approach for treating I/R.

Language: Английский

Citations

17
Cardiac MRI Strain as an Early Indicator of Myocardial Dysfunction in Hypertrophic Cardiomyopathy DOI Open Access
Siqin Liu, Oumaima Laghzali,

Shahriar Shalikar

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1407 - 1407

Published: Feb. 7, 2025

Hypertrophic cardiomyopathy (HCM) is often characterized by augmented cardiac contractility, which frequently remains undetectable in its early stages. Emerging evidence suggests that hypercontractility linked to mitochondrial defects develop HCM progression. However, imaging markers for identifying these alterations myocardial function are lacking. We used magnetic resonance feature tracking (CMR-FT) assess strain a Mybpc3-knockin (KI) mouse model mimicked human HCM. While homozygous (HOM) mice exhibited hypertrophy, heterozygous (HET) represented an early, asymptomatic stage of To explore contributions hypercontractility, we evaluated integrity via scanning electron microscopy (SEM) and correlated findings with abnormalities. Young HET female, but not male significant torsion abnormalities (p = 0.02), reduced left ventricular global longitudinal (LVGLS, p 0.009), impaired right (RVGLS, 0.035) compared the controls. Strain strongly morphological alterations, including changes volume area distribution (R > 0.7). Abnormal patterns, GLS, serve as closely associated underlying dysfunction. The Mybpc3-KI provides important insights into initial stages progression, highlighting sex-specific differences enhance diagnosis therapeutic strategies.

Language: Английский

Citations

1
The CGAS-STING1 Pathway as a Mediator of Innate Immune Response in Cardiovascular Disease DOI Creative Commons
Leila Rouhi, Priyatansh Gurha, Ali J. Marian

et al.

JACC Asia, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Identification and validation of mitochondrial dynamics-related genes in patients with acute myocardial infarction-a bioinformatics analysis DOI Creative Commons

Xiaolin Yue,

Jinlei Wu,

Xue-yun Shi

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract Recent studies highlight the link between cardiovascular disease and mitochondrial dynamics. This study sought biomarkers of dynamics in acute myocardial infarction (AMI) to guide more precise clinical management. AMI-related datasets (GSE62646 GSE59867) 50 dynamics-related genes (MD-RGs) were derived from public databases. Firstly, based on MD-RGs, AMI samples GSE62646 classified into high- low-scoring groups by single-sample gene set enrichment analysis. The differentially expressed (DEGs) incorporated machine learning algorithms. Subsequent expression level receiver operating characteristic (ROC) analyses identified biomarkers. Furthermore, relationship was analyzed analysis, immune infiltration correlation analysis m6A regulators. Finally, biomarker verified reverse transcription quantitative PCR (RT-qPCR). In this study, COX7B SNORD54 as associated with AMI. ROC curves showed that two could better differentiate control samples, subsequent nomogram created integrating highly accurate predicting revealed co-enrich pathways for included “oxidative phosphorylation” “Notch signaling pathway”. Notably, six regulators (HNRNPC, KIAA1429, METTL3, WTAP, YTHDC1, YTHDC2) found be significantly under-expressed samples. RT-PCR demonstrated levels downregulated compared controls. recognized AMI, presenting potential applications advance understanding

Language: Английский

Citations

0
Clinical Perspectives for Diagnosis and Treatment of Diabetic Cardiomyopathy DOI
David Chen, Andrew Sindone, Michael Huang

et al.

Published: Jan. 1, 2025

Diabetes mellitus is associated with significant morbidity and premature mortality for which heart failure (HF) a major cause. HF may be due to ischaemia, hypertension, uraemia, or specific diabetic cardiomyopathy (DCM), multiple causes co-exist. A recent systematic review suggests that >40% of people type 2 diabetes have diastolic dysfunction without reduction cardiac systolic function. In 1 known cardiovascular disease, 16% had dysfunction. Early DCM asymptomatic can progress symptomatic via increasing cardiomyocyte hypertrophy death as well fibrosis. The 5-year rate similar worse than many common cancers. There been advances in treatment including sodium-glucose co-transport inhibitors (SGLT2i) angiotensin receptor-neprilysin (ARNi), promising therapies such finerenone glucagon-like peptide-1 receptor agonists (GLP-1RA). SGLT2i, finerenone, GLP-1RA also role prevention DCM. While there currently no goes beyond general treatment, research into innovative technologies gene stem cell therapies. Also, digital will likely an treatment. Herein we the pathophysiology, diagnosis, DCM, focus on existing, emerging, potentially novel We provide practical tables summarise at each stage important practice points commonly prescribed drugs.

Language: Английский

Citations

0
Mechanisms of mitochondrial damage-associated molecular patterns associated with inflammatory response in cardiovascular diseases DOI

Xiuju Guan,

Haitao Li,

Lijuan Zhang

et al.

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Jan. 13, 2025

Language: Английский

Citations

0
The role of exercise in bolstering cardiac resilience during aging DOI Open Access
Ankur Singh Saini, Kirsty Foote, Martin R. Bennett

et al.

The Journal of Cardiovascular Aging, Journal Year: 2025, Volume and Issue: 5(1)

Published: Jan. 15, 2025

Aging leads to structural and functional deterioration of the heart, reducing its capacity withstand internal external stressors consequently increasing risk heart failure. Exercise is a potent modulator cardiovascular metabolic health, offering numerous physiological benefits that can persist throughout aging process. Studies suggest exercise decelerate age-related cardiac mitigate In this review, we discuss recent advances in our understanding exercise-mediated molecular cellular adaptations could serve as therapeutic targets for remodeling decline. We also explore how exercise-induced changes may enhance resilience with age, examine sex differences response exercise, highlight value murine models research tools identifying novel strategies combat

Language: Английский

Citations

0
A look at MERCs as UPRmt regulatory hubs in age-associated heart diseases DOI Open Access

Gabriela Navarrete-Anastasio,

Zeltzin Alejandra Ceja-Galicia, Cecilia Zazueta

et al.

The Journal of Cardiovascular Aging, Journal Year: 2025, Volume and Issue: 5(1)

Published: Jan. 22, 2025

With the increase in life expectancy globally, challenge of dealing with aging becomes more prominent. Aging is a risk factor for several diseases, including cardiovascular disease. Mitochondria, which have long been studied relation to aging, play crucial role maintaining cellular homeostasis. However, there limitation interorganellar communication as organisms age. The unfolded protein response mitochondria (UPRmt) activated during stress maintain mitochondrial homeostasis and prevent accumulation damaged mitochondria. This involves signaling from nucleus, leading transcriptional changes. In context heart, this review explores terms function morphology. It also discusses impact UPRmt on cardiac diseases such heart failure, acute myocardial infarction, dilated cardiomyopathy. highlights potential mitochondria-endoplasmic reticulum contact sites (MERCs) modulating aging. Finally, it provides an update molecules that induce activity, potentially benefiting

Language: Английский

Citations

0
Zn2+ protects H9C2 cardiomyocytes by alleviating MAMs-associated apoptosis and calcium signaling dysregulation DOI

Jiabao Guo,

Tingting Ma,

Bingyu Wang

et al.

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111629 - 111629

Published: Jan. 1, 2025

Language: Английский

Citations

0
Mitochondrial damage-associated molecular patterns: New perspectives for mitochondria and inflammatory bowel diseases DOI Creative Commons
Zhijie Wang, Zi‐Xuan He, Xin Chang

et al.

Mucosal Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Mitochondria are key regulators of inflammatory responses and mitochondrial dysfunction is closely linked to various diseases. Increasing genetic experimental evidence suggests that mitochondria play a critical role in bowel disease (IBD). In the complex environment intestinal tract, epithelial cells (IECs) their possess unique phenotypic features, shaping each other regulating homeostasis inflammation through diverse mechanisms. Here, we focus on IBD induced by damage-associated molecular patterns (mtDAMPs), which comprise components metabolic products. The pathogenic mechanisms mtDAMP signaling pathways mediated two major mtDAMPs, DNA (mtDNA) reactive oxygen species (mtROS), discussed.

Language: Английский

Citations

0