ER stress improvement by aerobic training or enalapril differently ameliorates pathological cardiac remodeling in obese mice

• Published in: Molecular and cellular biochemistry
• Main Authors: Salles, Amanda Conceição Pimenta, Alexandre-Santos, Beatriz, de Souza Carvalho, Thais, Proença, Ana Beatriz, Sepúlveda-Fragoso, Vinicius, Fernandes, Tiago, Oliveira, Edilamar Menezes, da Nóbrega, Antonio Claudio Lucas, Frantz, Eliete Dalla Corte, Magliano, D'Angelo Carlo
• Format: Journal Article
• Language: English
• Published: Netherlands 03.02.2024
• Subjects: Obesity; Aerobic exercise training; Cardiac remodeling; Renin-angiotensin system; Endoplasmic reticulum stress
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-024-04925-1

Overactivation of the classic arm of the renin-angiotensin system (RAS) is one of the main mechanisms involved in obesity-related cardiac remodeling, and a possible relationship between RAS and ER stress in the cardiovascular system have been described. Thus, the aim of this study is to evaluate if activating the protective arm of the RAS by ACE inhibition or aerobic exercise training could overturn diet-induced pathological cardiac hypertrophy by attenuating ER stress. Male C57BL/6 mice were fed a control (SC) or a high-fat diet (HF) for 16 weeks. In the 8th week, HF-fed animals were randomly divided into HF, enalapril treatment (HF-En), and aerobic exercise training (HF-Ex) groups. Body mass (BM), food and energy intake, plasma analyzes, systolic blood pressure (SBP), physical conditioning, and plasma ACE and ACE2 activity were evaluated. Cardiac morphology, and protein expression of hypertrophy, cardiac metabolism, RAS, and ER stress markers were assessed. Data presented as mean ± standard deviation and analyzed by one-way ANOVA with Holm-Sidak post-hoc. HF group had increased BM and SBP, and developed pathological concentric cardiac hypertrophy, with overactivation of the classic arm of the RAS, and higher ER stress. Both interventions reverted the increase in BM, and SBP, and favored the protective arm of the RAS. Enalapril treatment improved pathological cardiac hypertrophy with partial reversal of the concentric pattern, and slightly attenuated cardiac ER stress. In contrast, aerobic exercise training induced physiological eccentric cardiac hypertrophy, and fully diminished ER stress.