Proanthocyanidins-Rich Euterpe oleracea Mart Seed Extract Prevents Vascular and Perivascular Adipose Tissue Remodeling by Regulating the Renin-Angiotensin System, Inflammation, and Oxidative Damage in Diet-Induced Obese Mice

Abstract

Ectopic excessive fat deposition, including the perivascular adipose tissue (PVAT), may negatively influence vascular homeostasis and has emerged as a target for treating obesity-related vascular disease. The açaí ( Euterpe oleracea Mart) seed extract (ASE) has beneficial metabolic effects, which could reduce the risk of obesity-related vascular disease. Therefore, this study aimed to investigate the impact of treatment with ASE on aorta remodeling and hypertension and evaluate its underlying mechanisms in a mouse model of obesity induced by a high-fat (HF) diet. Male C57BL/6 mice were divided into the groups: Control, HF, and HF + ASE (300 mg/kg/day for 12 weeks). We evaluated the systolic and diastolic blood pressure, PVAT, and aorta morphology and fibrosis parameters. Renin-angiotensin system (RAS) proteins, oxidative stress, and inflammatory biomarkers were evaluated in the aorta and PVAT by Western blotting and/or immunohistochemistry. ASE impaired weight gain, hypertension, PVAT hypertrophy and aorta morphological changes (media thickness, media-to-lumen ratio, and circumferential wall tension). ASE prevented the fibrosis by mitigating the increased deposition of type I collagen and TGF- β . The increased RAS components in the aorta (renin, AT1R) and PVAT (AT1R), as well as the decreased ACE2/ACE (aorta) and AT2R (PVAT), were prevented by ASE. The overexpression of oxidative damage markers (NOX4 and 8-isoprostane) and pro-inflammatory cytokines (IL-6, TNF- α , and MCP-1) was impaired by ASE. The study indicates that ASE protects HF-fed mice from hypertension, PVAT and vascular wall remodeling by regulating PVAT and aortic RAS, as well as oxidative stress and inflammation.