Aim: As technological interventions treating acute myocardial infarction (MI) improve, post-ischemic heart failure increasingly threatens patient health. The aim of the current study was to test whether FADD could be a potential target of gene therapy in the treatment of heart failure.
Methods: Cardiomyocyte-specific FADD knockout mice along with non-transgenic littermates (NLC) were subjected to 30 minutes myocardial ischemia followed by 7 days of reperfusion or 6 weeks of permanent myocardial ischemia via the ligation of left main descending coronary artery. Cardiac function were evaluated by echocardiography and left ventricular (LV) catheterization and cardiomyocyte death was measured by Evans blue-TTC staining, TUNEL staining, and caspase-3, -8, and -9 activities. In vitro, H9C2 cells transfected with ether scramble siRNA or FADD siRNA were stressed with chelerythrin for 30 min and cleaved caspase-3 was assessed.
Results: FADD expression was significantly decreased in FADD knockout mice compared to NLC. Ischemia/reperfusion (I/R) upregulated FADD expression in NLC mice, but not in FADD knockout mice at the early time. FADD deletion significantly attenuated I/R-induced cardiac dysfunction, decreased myocardial necrosis, and inhibited cardiomyocyte apoptosis. Furthermore, in 6 weeks long term permanent ischemia model, FADD deletion significantly reduced the infarct size (from 41.20 ± 3.90% in NLC to 26.83 ± 4.17% in FADD deletion), attenuated myocardial remodeling, improved cardiac function and improved survival. In vitro, FADD knockdown significantly reduced chelerythrin-induced the level of cleaved caspase-3.
Conclusion: Taken together, our results suggest FADD plays a critical role in post-ischemic heart failure. Inhibition of FADD retards heart failure progression. Our data supports the further investigation of FADD as a potential target for genetic manipulation in the treatment of heart failure.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3772851 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073537 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
A STRONG call for intensive oral heart failure therapy in acute heart failure patients.
Heart Fail Rev
January 2025
Department of Anesthesiology and Critical Care, Université Paris Cité, Paris, France.
Heart failure (HF), a chronic and progressive disease, is increasing in prevalence worldwide and is associated with increased hospitalizations and death. Despite notable improvements in medical therapy for HF, patients are still at risk of future negative outcomes. Current guidelines recommend four classes of medication for treating patients with HF, deemed guideline-directed medical therapy (GDMT).
View Article and Find Full Text PDFHeart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are increasingly prevalent cardiovascular conditions, particularly among the elderly population. These two conditions share common risk factors and often coexist, leading to a complex interplay that alters the clinical course of each other. The pathophysiology of HFpEF is multifaceted and intricately linked, with atrial disease serving as a common pathophysiological pathway.
View Article and Find Full Text PDFGlobal burden of heart failure in children and adolescents from 1990 to 2019: an analysis from the Global Burden of Disease Study 2019.
World J Pediatr
January 2025
Cardiac Arrhythmia Center, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing, 100037, China.
Background: Heart failure (HF) significantly impacts the cardiovascular health of children and adolescents. This study aims to assess epidemiologic trends in HF across sex, age, region, and time period.
Methods: The number and age-standardized rate (ASR) of prevalence and years lived with disability (YLDs) were derived from the Global Burden of Disease Study 2019.
The relationship between cannabis and cardiovascular disease: clearing the haze.
Nat Rev Cardiol
January 2025
Stanford Cardiovascular Institute, Stanford, CA, USA.
Cannabis has been consumed for centuries, but global regulatory changes over the past three decades have increased the availability and consumption of cannabis. Cannabinoids are touted to have therapeutic potential for many diseases and could be a replacement for opioids for analgesia and sedation. However, cannabinoids can cause substantial adverse cardiovascular events that would mitigate any potential benefit.
View Article and Find Full Text PDFEffects of aortic valve calcification on transcatheter aortic valve replacement for low-flow, low-gradient aortic stenosis.
Cardiovasc Revasc Med
January 2025
Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:
Background: Patients with low-flow, low-gradient (LFLG) aortic stenosis (AS) have precarious hemodynamics and are a fragile population for intervention. Quantification of aortic valve calcification (AVC) severity is a critical component of the evaluation for transcatheter aortic valve replacement (TAVR); this study aims to further clarify its utility for risk stratification in LFLG AS.
Methods: This retrospective study evaluated 467 patients with LFLG AS undergoing TAVR at a large quaternary-care hospital from January 2019 to December 2021.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!