AT1-receptor blockade attenuates outward aortic remodeling associated with diet-induced obesity in mice

The renin-angiotensin-system and obesity have been implicated in vascular outward remodeling, including aneurysms, but the precise mechanisms are yet not understood. We investigated the effect of the angiotensin AT1-receptor antagonist telmisartan on aortic outward remodeling in a diet-induced obesity-model in mice. C57/Black6J mice were fed with either a low-fat diet (LFD), or a high-fat diet (HFD) for 14 weeks. One group of HFD-mice was additionally exposed to telmisartan (3mg/kg/d) for the last 4 weeks. HFD led to aortic outward remodeling, characterized by increased proteolysis, along with structural changes, such as fragmentation of elastic fibres, and decreased elastin content. Vascular damage was associated with upregulation of MMP-2, MMP-3, MMP-12, cathepsin D and cathepsin B. HFD aortae exhibited an enhanced inflammatory status, characterized by TNF-α and IL-1β co-localized with adipocytes in the adventitia. HFD resulted in a significant increase of aortic dimensions, evidenced by ultrasound measurements. Telmisartan abolished aortic dilatation and preserved elastin content. HFD-induced enhanced expression of aortic MMP-2, MMP-9 and TNF-α was abrogated by telmisartan. Adventitial proteolytic and inflammatory factors were also examined in samples from human abdominal aneurysms. The expression of TNF-α, IL-1β and MMP-9 was higher in the adventitial fat of diseased vessels compared with healthy tissues. Finally, adipocytes treated with TNF-&a...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research