PO-01-172 METABOLIC SHIFT CONTRIBUTES TO SINOATRIAL NODE DYSFUNCTION IN HEART FAILURE WITH PRESERVED EJECTION FRACTION
نویسندگان
چکیده
Cardiometabolic alterations are frequent in patients with heart failure preserved ejection fraction (HFpEF). We recently demonstrated sinoatrial node (SAN) dysfunction limits the chronotropic response two distinct animal models of HFpEF; however, our new findings suggest a relationship between metabolism and SAN dysfunction. To identify metabolically-driven changes that facilitate HFpEF. Male C57Bl6 mice fed high fat (HFD) plus nitric oxide inhibitor (L-NAME) diet or regular chow served as HFpEF controls, respectively. Transcriptomics, metabolomics, targeted quantitative proteomics mitochondria, optical mapping preparations from control HFpEF-verified were performed. animals after 20 weeks HFD+LNAME exhibited prolonged recovery time (100%; P<0.05). A combination multi-omics studies revealed metabolic gene clusters suggesting shift towards glycolysis source energy. Supporting these findings, isolated mitochondria SANs showed depressed maximal mitochondrial respiration compared to controls (-42%; In addition, pacemaker cells increased reactive oxygen species production (+70%; Moreover, acute uncoupling induced by FCCP elicited pronounced prolongation (165%; Our results is closely associated remodeling energetic substrate shift. However, further needed establish causality
منابع مشابه
Heart Failure With Preserved Ejection Fraction
The Journal of the American Osteopathic Association July 2015 | Vol 115 | No. 7 432 From Henry Ford Wyandotte Downriver Cardiology in Brownstown, Michigan (Dr Rogers); West Suburban Medical Center in Oak Park, Illinois (Dr Gundala); Oakwood Southshore Medical Center in Trenton, Michigan (Dr Ramos); and Elmhurst Memorial Hospital in Illinois (Dr Serajian). Drs Gundala and Ramos are in their thir...
متن کاملHeart Failure With Preserved Ejection Fraction
Symptomatic heart failure, despite preserved left ventricular (LV) ejection fraction, is a well-recognized phenomenon. This manifestation of diastolic dysfunction is associated with increased morbidity and mortality and can be attributed to a variety of pathogeneses, including diabetes mellitus, hypertension, infiltrative processes, and obesity. Unlike in systolic heart failure, where LV ejecti...
متن کاملHeart Failure with Preserved Ejection Fraction
1. Demonstrate the association between heart failure with preserved ejection fraction (HFpEF) and survival. 2. Given a patient with heart failure (HF), recognize HFpEF on the basis of clinical signs and symptoms, physical examination, echocardiography, and radiographic findings. 3. Classify patients at high risk of hospitalization and mortality through assessing risk factors, clinical presentat...
متن کاملEndothelial Senescence Contributes to Heart Failure With Preserved Ejection Fraction in an Aging Mouse Model.
BACKGROUND Because of global aging, the prevalence of heart failure with preserved ejection fraction (HFpEF) continues to rise. Although HFpEF pathophysiology remains incompletely understood, endothelial inflammation is stated to play a central role. Cellular senescence is a process of cellular growth arrest linked with aging and inflammation. We used mice with accelerated aging to investigate ...
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ژورنال
عنوان ژورنال: Heart Rhythm
سال: 2023
ISSN: ['1556-3871', '1547-5271']
DOI: https://doi.org/10.1016/j.hrthm.2023.03.510