Year: 2026
Type: article
Abstract: Heart failure with preserved ejection fraction (HFpEF) is an extremely prevalent cardiovascular disease driven by a systemic inflammation pathway from co-morbidities such as cardiometabolic syndrome (CMS). CMS includes metabolic disorders such as abdominal obesity, hypertension, and dyslipidemia. Notable features of CMS-induced HFpEF include diastolic dysfunction, hypertrophy, and concentric left ventricular remodelling. Additionally, HFpEF is noted to be sex specific in prevalence and prognosis. Autophagy is a cellular quality control process that involves the recycling of damaged organelles and proteins. When reactive oxygen species, a harmful byproduct of cell functioning, build up, antioxidants and mitochondrial autophagy (mitophagy) must act to clear them. Previous research has connected autophagy to HFpEF; however, information is limited and even less is currently known about the cellular mechanisms underlying sex differences in HFpEF. Herein, we sought to investigate sex specific differences in autophagy and oxidative stress mechanisms in the pathogenesis of CMS-induced HFpEF. C57BL/6J male and female mice were fed a normal diet, high fat diet (HFD), or HFD + L-NAME for 5 or 8 weeks. Animals were assessed for cardiac function using non-invasive echocardiography prior to sacrifice. Hearts were processed for Western blot analysis and assessed for autophagy markers and anti-oxidant manganese superoxide dismutase (SOD2). mRNA was used to measure transcription of the mitophagy marker BNIP3 by quantitative real-time PCR (qPCR). Our findings show by echocardiography that HFpEF, but not heart failure with reduced ejection fraction (HFrEF), was induced in female and male mice fed HFD + L-NAME and that male mice have worse cardiac parameters than corresponding female mice. In tandem with this finding, female mice fed HFD + L-NAME showed increased autophagy compared to males and lacked the reduction in SOD2 observed in males. Our findings reveal a novel connection between male and female mice in autophagy regulation and cardiac dysfunction in cardiometabolic syndrome induced HFpEF.
Source: Mspace (University of Manitoba)
Author: Kowall, Charlotte
Institution: University of Manitoba
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7214143486