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

ISABEL QUESADA; BEATRIZ CANNIZZO; ISABEL QUESADA; BEATRIZ CANNIZZO; RODRIGO GARCIA; CLAUDIA CASTRO; RODRIGO GARCIA; CLAUDIA CASTRO; JIMENA CEJAS; ANALÍA REDONDO; JIMENA CEJAS; ANALÍA REDONDO

CARDIOVASCULAR THERAPEUTICS

WILEY-BLACKWELL PUBLISHING, INC

Año: 2018

1755-5914

AIM: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.METHODS: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.RESULTS: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: p22phox , Nox1, Nox2, Nox4 and p47phox , 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.CONCLUSION: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.