title: Pioglitazone Reduces Vascular Lipid Accumulation in Angiotensin II-Induced Hypertensive Rat.
abstract: OBJECTIVE
  In an insulin-resistant state, excess lipids may accumulate in various non-adipose tissues, leading to histological and functional damage. It has been suggested that peroxisome proliferator-activated receptor-gamma (PPARγ) may ameliorate disorganized lipid balance. In the current study, we analyzed whether pioglitazone, an agonist of PPARγ, reduces angiotensin II-induced vascular lipid accumulation.
  
  
  METHODS
  Angiotensin II was infused into rats at doses of 0.7 mg/kg/day via a subcutaneously implanted osmotic minipump for 7 consecutive days. Pioglitazone was orally given at a dose of 2.5 mg/kg/day for 7 days.
  
  
  RESULTS
  Pioglitazone significantly reduced angiotensin II-induced enhanced lipid deposition and superoxide production in the adventitia of the aorta, as detected by oil red O and dihydroethidium (DHE) staining, respectively. Increased DHE signals, some observed at the site of lipid deposition, were mainly localized in ED-1-positive monocytes/macrophages. Angiotensin II-induced upregulation of the expression of LDL receptor and Nox1 was inhibited by pioglitazone treatment. In addition, angiotensin II significantly reduced the expression of PCSK9, and this reduction was ameliorated by pioglitazone. On the other hand, pioglitazone did not significantly alter the expression of the phosphorylated forms of AMPKα and ACC, which was downregulated by angiotensin II.
  
  
  CONCLUSIONS
  Pioglitazone treatment suppressed excess lipid accumulation and superoxide production in the aorta in an angiotensin II-induced rat model of hypertension.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Higashikuni
authors.forename: Makiko
authors.initials: M
authors.lastname: Hongo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Imai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Ishizaka
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000804:Angiotensin II / Q000737:chemistry*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008297:Male; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D008055:Lipids; D047495:PPAR gamma; D045162:Thiazolidinediones; D013481:Superoxides; D000804:Angiotensin II; D055372:AMP-Activated Protein Kinases; D000077205:Pioglitazone