Evaluation of myocardial classic and alternative pathways of the renin-angiotensin system in cholestasis-induced cardiac injury: A time-course experimental study in rats | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 15، دوره 28، شماره 11، بهمن 2025، صفحه 1598-1606 اصل مقاله (429.27 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2025.87090.18818 | ||
| نویسندگان | ||
| Azadeh Khalili1؛ Parham Samimisedeh2؛ Mohammad Maleki2؛ Elmira Jafari Afshar2؛ Mohammad Jadidian3؛ Roham Mazloom1؛ Gholamreza Bayat* 1؛ Hossein Karim* 2، 4 | ||
| 1Department of Physiology-Pharmacology-Medical Physics, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran | ||
| 2Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran | ||
| 3Department of Pathology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran | ||
| 4Department of Cardiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran | ||
| چکیده | ||
| Objective(s): Cholestasis, characterized by impaired bile flow and elevated bile acid levels, can lead to cardiac dysfunction, termed Cholecardia syndrome. The pathophysiology of cholestasis-induced cardiac injury involves direct and indirect effects of bile acids through various molecular pathways. However, the role of the renin-angiotensin-aldosterone system (RAS), modulated by bile acids, remains unclear.This study aimed to investigate alterations in the expression of classic and alternative RAS components in the myocardium of rats with obstructive cholestasis in a six-week period. Materials and Methods: Forty-two male Wistar rats (8 weeks old, 250 ± 30 g) were randomly assigned to seven groups (n=6 per group): one sham-operated group and six bile duct ligation (BDL) groups, sacrificed at weekly intervals from 1 to 6 weeks post-surgery. Quantitative RT-PCR was used to analyze cardiac RAS component expression. Biochemical and histopathological evaluations were conducted to assess disease progression. Results: In the classic RAS pathway, myocardial angiotensin-converting enzyme (ACE) expression increased after week 4 of BDL, while angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) were significantly down-regulated in this period. In contrast, the alternative RAS pathway components, including ACE2 and the Mas receptor, exhibited a biphasic expression pattern in the myocardium, with down-regulation at week 3 followed by significant up-regulation at weeks 5–6. Conclusion: The findings reveal distinct alterations in RAS pathways during cholestasis-induced cardiac injury. The alternative RAS pathway may play a compensatory role in late-stage cholestasis, highlighting potential therapeutic targets for Cholecardia syndrome and cirrhotic cardiomyopathy. | ||
| کلیدواژهها | ||
| Angiotensin-converting - enzyme 2؛ Angiotensin receptors؛ Cholecardia syndrome؛ Cholestasis؛ Renin-angiotensin system | ||
| مراجع | ||
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