Cardioprotective and Antifibrotic Effects of Low-Dose Renin–Angiotensin–Aldosterone System Inhibitors in Type 1 Diabetic Rat Model
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Published:2023-12-01
Issue:23
Volume:24
Page:17043
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Balogh Dora B.12ORCID, Molnar Agnes2, Degi Arianna2, Toth Akos12, Lenart Lilla12ORCID, Saeed Adar12, Barczi Adrienn3, Szabo Attila J.2, Wagner Laszlo J.4ORCID, Reusz Gyorgy2ORCID, Fekete Andrea12
Affiliation:
1. MTA-SE Lendület “Momentum” Diabetes Research Group, 1083 Budapest, Hungary 2. Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary 3. Medical Imaging Center, Semmelweis University, 1082 Budapest, Hungary 4. Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1082 Budapest, Hungary
Abstract
Diabetic cardiovascular complications are associated with up to 50% mortality, and current therapies are not effective enough. Renin–angiotensin–aldosterone system inhibitors (RAASis) are the standard of care for diabetic patients with hypertension and albuminuria. Based on our previous studies reporting the renoprotective effects of low-dose RAASis, here, we hypothesized that low-dose RAASi treatment has cardioprotective and antifibrotic benefits in type 1 diabetes mellitus (T1DM). After five weeks of T1DM, adult male Wistar rats received low doses of ramipril, losartan, or eplerenone for two weeks. Heart rate, blood pressure, and pulse wave velocity (PWV) were recorded. Aortic intima–media thickness (IMT), collagen accumulation, and myocardial fibrosis were assessed. All RAASis reduced PWV elevation, prevented the progression of myocardial fibrosis, and normalized B-type natriuretic peptide, troponin I, and fibroblast growth factor 23 levels without affecting blood pressure. Interestingly, only eplerenone reversed the decline in Klotho levels and reduced IMT and fibrosis in the media of the aorta. Our comparative analysis suggests that mineralocorticoid receptor antagonists, particularly eplerenone, may offer superior efficacy in halting both the arterial and the myocardial injuries in T1DM compared to angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers.
Funder
Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund Hungarian Academy of Sciences
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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