Ac-SDKP and eplerenone confer additive cardioprotection against angiotensin II-induced cardiac injury in C57BL/6J mice
Recommended Citation
Hamid S, Sarkar S, Peng H, Khalid M, Ortiz PA, Xu J, Liao TD, Knight RA, and Rhaleb NE. Ac-SDKP and eplerenone confer additive cardioprotection against angiotensin II-induced cardiac injury in C57BL/6J mice. J Mol Cell Cardiol Plus 2025;14:100485.
Document Type
Article
Publication Date
12-1-2025
Publication Title
J Mol Cell Cardiol Plus
Keywords
Ac-SDKP; Angiotensin II; Cardiac dysfunction; Eplerenone; Hypertension
Abstract
Eplerenone, a mineralocorticoid receptor antagonist, is an anti-hypertensive and cardioprotective drug. We showed that N-Acetyl-Seryl-Aspartyl-Proline (Ac-SDKP) exerts beneficial effects on the heart. Whether Ac-SDKP provides additional cardioprotective effects if combined with eplerenone in angiotensin II (Ang II)-induced hypertension remains unknown. Male C57BL/6J mice were treated with either sham, Ang II (2.9 mg/kg/day, s.c.), Ang II + Ac-SDKP (1.6 mg/kg/day, s.c.), Ang II + Eplerenone (150 mg/kg/day in mouse chow), or Ang II + Ac-SDKP + Eplerenone. Treatment lasted for eight weeks. Systolic blood pressure (SBP) measurements were taken weekly. Echocardiography (Echo) and magnetic resonance imaging (MRI) were performed at the end of the experiment. SBP was increased in all mice with Ang II and was not affected by any treatment. Posterior wall thickness (PWT) and left ventricular (LV) mass were increased in Ang II-treated groups. LV mass was not significantly affected by treatment, but PWT was reduced by both monotherapies and showed the greatest reduction with combined Ac-SDKP and eplerenone. Ejection fraction (EF) decreased in the Ang II group compared to the sham group. EF increased with all treatments (MRI), and there was a further significant increase in EF for mice treated with Ac-SDKP + Eplerenone compared to those receiving a single treatment (Echo). Our data indicate that treatment with Ac-SDKP or Eplerenone improves cardiac function in Ang II-induced hypertension, and supplying Ac-SDKP to Eplerenone provides additive, not synergistic, cardioprotective effects. These beneficial effects were associated with decreased myocardial collagen accumulation, CD68-positive macrophage infiltration, and the expression of CHOP, an endoplasmic reticulum stress mediator. Ac-SDKP could be an effective supplementary treatment alongside Eplerenone for managing hypertension-associated cardiac damage and dysfunction.
PubMed ID
41048927
Volume
14
First Page
100485
Last Page
100485
