Differential Myocardial Responses in Male and Female Rats with Uremic Cardiomyopathy
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Published on: November 29, 2024
Beáta Bódi1, Rebeka Rita Vágó1, László Nagy1,2
1Division of Clinical Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Insights
Male rats develop more severe uremic cardiomyopathy, a complication of chronic kidney disease (CKD), than female rats. This includes greater left ventricular hypertrophy, diastolic dysfunction, and fibrosis in males.
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.
Abstract:
Uremic cardiomyopathy, characterized by diastolic dysfunction, left ventricular hypertrophy (LVH), and fibrosis, is a common cardiovascular complication of chronic kidney disease (CKD). Men are at a higher risk for cardiovascular and renal diseases, compared to age-matched, pre-menopausal women. We aimed to investigate the influence of sex on the severity of uremic cardiomyopathy through the characterization of functional and molecular indices of myocardial remodeling in a rat model. CKD was induced by a 5/6 nephrectomy in 9-week-old male and female Wistar rats. Serum and urine tests, transthoracic echocardiography, left ventricular (LV) histology, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were performed at week 8 or 9. Moreover, LV alterations were also tested in permeabilized cardiomyocytes (CMs) by force measurements and Western immunoblotting. CKD resulted in the development of a more severe uremic cardiomyopathy in male rats-including LVH, LV diastolic dysfunction, and fibrosis-than in female rats, where only LVH was observed. A uremic cardiomyopathy was also associated with a decrease in maximal Ca2+-activated force (Fmax) in CMs of male rats. Additionally, increases in CM Ca2+-independent passive stiffness (Fpassive) and decreases in cardiac myosin-binding protein C (cMyBP-C) phosphorylation levels were significantly larger in male than female rats. In conclusion, a uremic cardiomyopathy involved cardiac remodeling in both sexes. Nevertheless, male rats exhibited more pronounced signs of macroscopic and microscopic alterations than their female counterparts, illustrating a sex-dependent component of uremic cardiomyopathy.
