Differential Myocardial Responses in Male and Female Rats with Uremic Cardiomyopathy

Area of Science:

• Cardiovascular Research
• Nephrology
• Sex Differences in Disease

Background:

• Uremic cardiomyopathy, a complication of chronic kidney disease (CKD), involves diastolic dysfunction, left ventricular hypertrophy (LVH), and fibrosis.
• Men face higher risks for cardiovascular and renal diseases than age-matched women.

Purpose of the Study:

• To investigate the influence of sex on the severity of uremic cardiomyopathy.
• To characterize functional and molecular indices of myocardial remodeling in a rat model of CKD.

Main Methods:

• CKD induced by 5/6 nephrectomy in male and female Wistar rats.
• Evaluated serum/urine, echocardiography, LV histology, RT-qPCR, and cardiomyocyte force measurements.
• Western immunoblotting assessed cardiac myosin-binding protein C phosphorylation.

Main Results:

• Male rats exhibited more severe uremic cardiomyopathy, including LVH, diastolic dysfunction, and fibrosis, compared to females (LVH only).
• Maximal Ca2+-activated force (Fmax) decreased in male cardiomyocytes.
• Increased Ca2+-independent passive stiffness (Fpassive) and decreased cMyBP-C phosphorylation were greater in males.

Conclusions:

• Uremic cardiomyopathy involves cardiac remodeling in both sexes.
• Male rats displayed more pronounced macroscopic and microscopic alterations, indicating a sex-dependent component.
• Findings highlight sex-specific differences in CKD-related heart disease progression.