Open AccessSGLT2 inhibitor dapagliflozin prevents atherosclerotic and cardiac complications in experimental type 1 diabetes
Author(s) -
Judit Hodrea,
Adar Saeed,
Ágnes Molnár,
Attila Fintha,
Adrienn Bárczi,
László Wagner,
Attila Szabó,
Andrea Fekete,
Dóra Balogh
Publication year - 2022
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0263285
Subject(s) - dapagliflozin , diabetes mellitus , medicine , type 2 diabetes , disease , cardiac hypertrophy , heart failure , cardiac fibrosis , inflammation , fibrosis , endocrinology , pharmacology
Cardiovascular disease (CVD) is two to five times more prevalent in diabetic patients and is the leading cause of death. Therefore, identification of novel therapeutic strategies that reduce the risk of CVD is a research priority. Clinical trials showed that reduction in the relative risk of heart failure by sodium-glucose cotransporter 2 inhibitors (SGLT2i) are partly beyond their glucose lowering effects, however, the molecular mechanisms are still elusive. Here we investigated the role of SGLT2i dapagliflozin (DAPA) in the prevention of diabetes-induced cardiovascular complications. Methods Type 1 diabetes was induced with streptozotocin (65 mg/bwkg, ip .) in adult, male Wistar rats. Following the onset of diabetes rats were treated for six weeks with DAPA (1 mg/bwkg/day, po .). Results DAPA decreased blood glucose levels (D: 37±2.7 vs . D+DAPA: 18±5.6 mmol/L; p<0.05) and prevented metabolic decline. Aortic intima-media thickening was mitigated by DAPA. DAPA abolished cardiac hypertrophy, and myocardial damage. Cardiac inflammation and fibrosis were also moderated after DAPA treatment. Conclusions These data support the preventive and protective role of SGLT2i in diabetes-associated cardiovascular disease. SGLT2i may provide novel therapeutic strategy to hinder the development of cardiovascular diseases in type 1 diabetes, thereby improve the outcomes.