Vascular dysfunction elicited by a cross talk between periaortic adipose tissue and the vascular wall is reversed by...

Perivascular adipose tissue (PVAT) is in intimate contact with the vessel wall and extravascular PVAT-derived inflammatory mediators may adversely influence atherosclerotic plaque formation and stability through outside-to-inside signaling. We sought to investigate the role of PVAT on the atheroma development in an experimental animal model of metabolic syndrome (MS) associated with oxidative stress and low-grade inflammatory state. We also studied the effect of pioglitazone an insulin sensitizer, on the aortic wall and its surrounding PVAT, considering a bi-directional communication between both layers.

Apolipoprotein E-deficient mice (ApoE^-/- ) were fed with standard diet (CD, control diet) or fructose overload (10% w/v) (FD, fructose diet) for 8 weeks and treated with or without pioglitazone the latest 4 weeks.

Biochemical variables show that glycemia and lipid peroxidation determined by thiobarbituric acid reactive species (TBARS) significantly increased in FD-fed ApoE^-/- mice. FD significantly increased aortic PVAT expression of oxidative stress associated genes: p22^phox , Nox1, Nox2, Nox4 and p47^phox , and proinflammatory genes: Visfatin, MCP-1, and MMP-9. Pioglitazone diminished PVAT-oxidative damage elicited by fructose treatment and markedly down-regulated proinflammatory markers. Even pioglitazone did not prevent the development of the aortic atheroma plaques stimulated by FD, significantly diminished VCAM-1 expression, MMP-9 expression and activity in aortic media wall and significantly reduced the accumulation of lipids and macrophages in atheroma plaques.

Our results support the fact that PVAT contributes to the development and progression of cardiovascular disease by underlying mechanisms elicited by "outside-in" signaling. Treatment with pioglitazone may offer a new effect on the whole vessel wall, promoting the stability of advanced atherosclerotic plaques.