Abstract
Abdominal aortic aneurysm (AAA) is a kind of disease characterized by aortic dilation, whose pathogenesis is linked to inflammation. This study aimed to determine whether grape-seed polyphenols (GSP) has anti-AAA effects and what mechanism is involved, thus to find a way to prevent occurrence and inhibit expansion of small AAA. In our study, AAA was induced by incubating the abdominal aorta of the mice with elastase, and GSP was administrated to the mice by gavage at different doses beginning on the day of the AAA inducement. In in vivo experiments, 800 mg/kg GSP could significantly reduce the incidence of AAA, the dilatation of aorta and elastin degradation in media, and dramatically decrease macrophage infiltration and activation and expression of matrix metalloproteinase (MMP) −2 and MMP-9 in the aorta, compared to the AAA model group. Meanwhile, 400 mg/kg GSP could also but not completely inhibit the occurrence and development of AAA. In in vitro experiments, GSP dose-dependently inhibited mRNA expression of interleukin (IL)-1β, IL-6 and monocyte chemoattractant protein-1 (MCP-1), and significantly inhibited expression and activity of MMP-2 and MMP-9, thus prevented elastin from degradation. In conclusion, GSP showed great anti-AAA effects and its mechanisms were related to inhibition of inflammation.
Highlights
A series of studies have provided crucial findings about the pathogenesis of Abdominal aortic aneurysm (AAA), including infiltration of lymphocytes and macrophages into the aneurysmal lesion, synthesis and excretion of inflammatory mediators and protease, degradation of elastin and collagen in the media and adventitia, apoptosis of vascular smooth muscle cells (VSMCs) induced by inflammatory response, as well as destruction of arterial wall and expansion of aortic lumen[7]
In comparison with the AngII-induced AAA model, the elastase-induced AAA model has high morbidity and low mortality, and the aneurysm occurs in the infra-renal region while AngII-induced AAA occurs in the suprarenal abdominal aorta[14, 15]
The anti-AAA effects of grape-seed polyphenols (GSP) were evaluated in vivo in an elastase-induced AAA mouse model
Summary
A series of studies have provided crucial findings about the pathogenesis of AAA, including infiltration of lymphocytes and macrophages into the aneurysmal lesion, synthesis and excretion of inflammatory mediators and protease (especially matrix metalloproteinases, MMPs), degradation of elastin and collagen in the media and adventitia, apoptosis of vascular smooth muscle cells (VSMCs) induced by inflammatory response, as well as destruction of arterial wall and expansion of aortic lumen[7]. The pathological process of AAA formation is related to inflammation. Plant polyphenols are known for their beneficial effects on cardiovascular diseases, which are largely associated with their anti-oxidant and anti-inflammatory properties. In the past two decades, grape-seed polyphenols (GSP), including a large group of flavonoids, such as epicatechin, flavanols, anthocyanins, etc., have been demonstrated to have significant effects of anti-inflammation and anti-oxidant, which may contribute to the inhibition of AAA8. The present study was designed to verify the hypothesis that GSP has anti-AAA effects and the mechanism is related to its anti-inflammation effects.
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