Exercise Therapy Rescues Skeletal Muscle Dysfunction and Exercise Intolerance in Cardiometabolic HFpEF.

Exercise intolerance, a hallmark of heart failure with preserved ejection fraction (HFpEF) exacerbated by obesity, involves unclear mechanisms related to skeletal muscle metabolism. In a "2-hit" model of HFpEF, we investigated the ability of exercise therapy (voluntary wheel running) to reverse skeletal muscle dysfunction and exercise intolerance. Using state-of-the-art metabolic cages and a multiomic approach, we demonstrate exercise can rescue dysfunctional skeletal muscle lipid and branched-chain amino acid oxidation and restore exercise capacity in mice with cardiometabolic HFpEF.

Dysregulation of Nitrosylation Dynamics Promotes Nitrosative Stress and Contributes to Cardiometabolic Heart Failure with Preserved Ejection Fraction.

Background: Recent reports suggest increased myocardial iNOS expression leads to excessive protein -nitrosylation, contributing to the pathophysiology of HFpEF. However, the relationship between NO bioavailability, dynamic regulation of protein -nitrosylation by trans- and de-nitrosylases, and HFpEF pathophysiology has not been elucidated. Here, we provide novel insights into the delicate interplay between NO bioavailability and protein -nitrosylation in HFpEF.

Protective role of 3-mercaptopyruvate sulfurtransferase (MPST) in the development of metabolic syndrome and vascular inflammation.

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that occur concurrently and increase the risk of cardiovascular disease. 3-mercaptopyruvate sulfurtransferase (MPST) is a cysteine-catabolizing enzyme that yields pyruvate and hydrogen sulfide (HS) and plays a central role in the regulation of energy homeostasis. Herein, we seek to investigate the role of MPST/HS in MetS and its cardiovascular consequences using a mouse model of the disease.

A Bifunctional Sulfide Donor Approach for Ischemic Stroke: Leveraging Butylphthalide as a Carrier for Sulfide Prodrug.

The physiological and pharmacological benefits of hydrogen sulfide (HS) are well established, and various HS and persulfide donors have been developed. However, few studies have examined the pharmacokinetics of sulfur donors, as most activity and metabolism tests are conducted , limiting insights into their clinical applications. This study utilized butylphthalide (NBP), an approved drug for ischemic stroke, by integrating HS and persulfide moieties directly into NBP's carbonyl groups.