Cardioprotective and Antifibrotic Effects of Low-Dose Renin–Angiotensin–Aldosterone System Inhibitors in Type 1 Diabetic Rat Model
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 repo...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/23/17043 |
| _version_ | 1797400047720071168 |
|---|---|
| author | Dora B. Balogh Agnes Molnar Arianna Degi Akos Toth Lilla Lenart Adar Saeed Adrienn Barczi Attila J. Szabo Laszlo J. Wagner Gyorgy Reusz Andrea Fekete |
| author_facet | Dora B. Balogh Agnes Molnar Arianna Degi Akos Toth Lilla Lenart Adar Saeed Adrienn Barczi Attila J. Szabo Laszlo J. Wagner Gyorgy Reusz Andrea Fekete |
| author_sort | Dora B. Balogh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T01:48:56Z |
| format | Article |
| id | doaj.art-6d4cc210497e44c2aa2b30e04ac1b698 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T01:48:56Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6d4cc210497e44c2aa2b30e04ac1b6982023-12-08T15:18:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124231704310.3390/ijms242317043Cardioprotective and Antifibrotic Effects of Low-Dose Renin–Angiotensin–Aldosterone System Inhibitors in Type 1 Diabetic Rat ModelDora B. Balogh0Agnes Molnar1Arianna Degi2Akos Toth3Lilla Lenart4Adar Saeed5Adrienn Barczi6Attila J. Szabo7Laszlo J. Wagner8Gyorgy Reusz9Andrea Fekete10MTA-SE Lendület “Momentum” Diabetes Research Group, 1083 Budapest, HungaryPediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, HungaryPediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, HungaryMTA-SE Lendület “Momentum” Diabetes Research Group, 1083 Budapest, HungaryMTA-SE Lendület “Momentum” Diabetes Research Group, 1083 Budapest, HungaryMTA-SE Lendület “Momentum” Diabetes Research Group, 1083 Budapest, HungaryMedical Imaging Center, Semmelweis University, 1082 Budapest, HungaryPediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, HungaryDepartment of Surgery, Transplantation and Gastroenterology, Semmelweis University, 1082 Budapest, HungaryPediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, HungaryMTA-SE Lendület “Momentum” Diabetes Research Group, 1083 Budapest, HungaryDiabetic 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.https://www.mdpi.com/1422-0067/24/23/17043diabetesdiabetic cardiomyopathyheart failurerenin–angiotensin–aldosterone system inhibitorsmyocardial fibrosisintima–media thickness |
| spellingShingle | Dora B. Balogh Agnes Molnar Arianna Degi Akos Toth Lilla Lenart Adar Saeed Adrienn Barczi Attila J. Szabo Laszlo J. Wagner Gyorgy Reusz Andrea Fekete Cardioprotective and Antifibrotic Effects of Low-Dose Renin–Angiotensin–Aldosterone System Inhibitors in Type 1 Diabetic Rat Model International Journal of Molecular Sciences diabetes diabetic cardiomyopathy heart failure renin–angiotensin–aldosterone system inhibitors myocardial fibrosis intima–media thickness |
| title | Cardioprotective and Antifibrotic Effects of Low-Dose Renin–Angiotensin–Aldosterone System Inhibitors in Type 1 Diabetic Rat Model |
| title_full | Cardioprotective and Antifibrotic Effects of Low-Dose Renin–Angiotensin–Aldosterone System Inhibitors in Type 1 Diabetic Rat Model |
| title_fullStr | Cardioprotective and Antifibrotic Effects of Low-Dose Renin–Angiotensin–Aldosterone System Inhibitors in Type 1 Diabetic Rat Model |
| title_full_unstemmed | Cardioprotective and Antifibrotic Effects of Low-Dose Renin–Angiotensin–Aldosterone System Inhibitors in Type 1 Diabetic Rat Model |
| title_short | Cardioprotective and Antifibrotic Effects of Low-Dose Renin–Angiotensin–Aldosterone System Inhibitors in Type 1 Diabetic Rat Model |
| title_sort | cardioprotective and antifibrotic effects of low dose renin angiotensin aldosterone system inhibitors in type 1 diabetic rat model |
| topic | diabetes diabetic cardiomyopathy heart failure renin–angiotensin–aldosterone system inhibitors myocardial fibrosis intima–media thickness |
| url | https://www.mdpi.com/1422-0067/24/23/17043 |
| work_keys_str_mv | AT dorabbalogh cardioprotectiveandantifibroticeffectsoflowdosereninangiotensinaldosteronesysteminhibitorsintype1diabeticratmodel AT agnesmolnar cardioprotectiveandantifibroticeffectsoflowdosereninangiotensinaldosteronesysteminhibitorsintype1diabeticratmodel AT ariannadegi cardioprotectiveandantifibroticeffectsoflowdosereninangiotensinaldosteronesysteminhibitorsintype1diabeticratmodel AT akostoth cardioprotectiveandantifibroticeffectsoflowdosereninangiotensinaldosteronesysteminhibitorsintype1diabeticratmodel AT lillalenart cardioprotectiveandantifibroticeffectsoflowdosereninangiotensinaldosteronesysteminhibitorsintype1diabeticratmodel AT adarsaeed cardioprotectiveandantifibroticeffectsoflowdosereninangiotensinaldosteronesysteminhibitorsintype1diabeticratmodel AT adriennbarczi cardioprotectiveandantifibroticeffectsoflowdosereninangiotensinaldosteronesysteminhibitorsintype1diabeticratmodel AT attilajszabo cardioprotectiveandantifibroticeffectsoflowdosereninangiotensinaldosteronesysteminhibitorsintype1diabeticratmodel AT laszlojwagner cardioprotectiveandantifibroticeffectsoflowdosereninangiotensinaldosteronesysteminhibitorsintype1diabeticratmodel AT gyorgyreusz cardioprotectiveandantifibroticeffectsoflowdosereninangiotensinaldosteronesysteminhibitorsintype1diabeticratmodel AT andreafekete cardioprotectiveandantifibroticeffectsoflowdosereninangiotensinaldosteronesysteminhibitorsintype1diabeticratmodel |