Female mice fed a high-fat diet and L-NAME developed HFpEF at 5 weeks, which worsened at 16 weeks, demonstrating susceptibility to HFpEF and associated complications.
Does a high-fat diet and L-NAME induce HFpEF and associated kidney and vascular complications in female mice?
Female mice are susceptible to developing HFpEF and associated kidney and vascular complications when exposed to metabolic and hypertensive risk factors, indicating female sex does not confer protection.
Introduction: The impact of female biological sex on the development of heart failure with preserved ejection fraction (HFpEF) and its associated kidney disease and vascular endothelial dysfunction is still controversial. Whether females are protected from HFpEF and associated complications is not well established. Previous studies report conflicting prevalence between genders. We hypothesize that female mice are unprotected from HFpEF and its associated kidney disease and vascular endothelial dysfunction. Methods: Eight-week-old female mice were divided into four groups: control groups receiving a standard diet and water for either 5 or 16 weeks, and HFpEF groups fed a high-fat diet (HFD, Rodent Diet With 60 kcal% Fat) and N w-nitro-l-arginine methyl ester (L-NAME - 0.5 g/L) in the drinking water for 5 or 16 weeks. Various measurements and assessments were performed, including echocardiography, metabolic and hypertensive evaluations, markers of heart and kidney injury, and assessment of vascular endothelial function. Results: Female mice with HFD and L-NAME developed HFpEF at 5 weeks, evidenced by increased E/E' ratio, reduced cardiac index, left ventricular mass, and unchanged ejection fraction. After 16 weeks, HFpEF worsened. Metabolic disorders, hypertension, lung wet/kidney weight increase, exercise intolerance, and cardiac/renal injury markers were observed. Vascular endothelial dysfunction was associated with ER stress and fibrosis induction. Conclusions: We found that female mice are susceptible to the development of HFpEF and its associated kidney disease and vascular endothelial dysfunction. Our data support the concept that the female sex does not protect from HFpEF and its associated kidney disease and vascular endothelial dysfunction when disease risk factors are present.
Srinivas et al. (Fri,) conducted a other in Heart failure with preserved ejection fraction (HFpEF). High-fat diet (HFD) and L-NAME vs. Standard diet and water was evaluated on Development of HFpEF. Female mice fed a high-fat diet and L-NAME developed HFpEF at 5 weeks, which worsened at 16 weeks, demonstrating susceptibility to HFpEF and associated complications.