Abstract 10890: Pioglitazone Ameliorates Vascular Lipid Accumulation in a Rat Model of Angiotensin II-Induced Hypertension
Background: In an insulin resistant state, excess lipid may accumulate in various non-adipose tissues, leading to a histologic as well as functional damage. Peroxisome proliferator-activated receptor-gamma (PPARγ) may act favorably in such occasions via normalizing disorganized lipid balance. We have previously shown that pioglitazone, an agonist of PPARγ, inhibited lipid deposition in the heart and the kidney of angiotensin II-infused rats. The hypothesis that pioglitazone also reduces lipid accumulation in vascular tissues was analyzed.
Methods and Results: The pressor dose of angiotensin II was infused into rats by an osmotic minipump, and pioglitazone was given orally for 7 days. Increased lipid deposition was observed in the adventitia of aorta by angiotensin II, and this was suppressed by pioglitazone. Superoxide production, examined by dihydroethidium (DHE) staining, was increased by angiotensin II (285 ± 34%, P<0.001 versus control), which was also diminished by pioglitazone treatment (87 ± 5%, P=NS versus control). Increased DHE signals were present at the site of lipid deposition, which was mainly localized in ED-1-positive monocytes/macrophages. Angiotensin II-induced upregulation of Nox1 mRNA expression (565 ± 94%, P<0.001 versus control) was suppressed by pioglitazone (298 ± 57%, P=NS versus control). In addition, upregulation of LDL receptor mRNA expression by angiotensin II (757 ± 227%, P<0.01 versus control) was inhibited by pioglitazone (314 ± 75%, P=NS versus control). Angiotensin II significantly reduced the expression of PCSK9 (39 ± 7%, P<0.01 versus control), which was improved by pioglitazone (74 ± 34%, P=NS versus control). On the other hand, reduced expression of phosphorylated forms of AMPKα (53 ± 11%, P<0.01 versus control) and ACC (48 ± 15%, P<0.05 versus control) by angiotensin II was unaffected by pioglitazone.
Conclusions: Pioglitazone reduced lipid accumulation and superoxide production in the aorta induced by angiotensin II. These findings collectively suggest that amelioration of aggravated lipid homeostasis and enhanced oxidative stress may represent a vasculoprotective property of PPARγ agonists in the activated renin-angiotensin system.
- © 2013 by American Heart Association, Inc.