[Rosiglitazone enhances the anti-atherosclerotic effects of peroxisome proliferator-activated receptor gamma1 gene transfer in apolipoprotein-knock out mice].
OBJECTIVE
To explore if PPARgamma agonist rosiglitazone could enhance the anti-atherosclerotic effects of mouse peroxisome proliferator-activated receptor gamma1 (PPARgamma1) gene transfer in apolipoprotein-knock out mice.


METHODS
Adult ApoE-knock out mice were fed a Western-diet for 20-weeks and then injected with PBS, Ad. PPARgamma1 (5 x 10(8)pfu) or Ad. GFP (5 x 10(8)pfu) via jugular vein. Another group of mice were intervened with rosiglitazone (dissolved in 0.5% cellulose acetate, 4 mg.kg(-1).d(-1), per gavage) 1 week before Ad. PPARgamma1 injection (n = 10, each group). Two weeks later, the lipid core and plaque composition were characterized with oil red O staining and Movat method respectively. The expression of PPARgamma, SM-actin, MOMA-2, MMP-9/TIMP-1, CD40/CD40L and TF antigens in aortic roots and plaques among four groups were compared semi-quantitatively using immunohistochemical technology.


RESULTS
All parameters were similar between AdGFP and PBS groups (P > 0.05). The area of plaque were significantly decreased and oil red O staining area significantly increased in AdPPARgamma1 [(0.86 +/- 0.12) mm(2), (150 +/- 35) x 10(3) microm(2)] and AdPPARgamma1 + RO [(0.79 +/- 0.15) mm(2), (270 +/- 49) x 10(3) microm(2)] treated mice compared with AdGFP group [(0.98 +/- 0.17) mm(2), (80 +/- 21) x 10(3) microm(2)] all P < 0.05. Elastic fiber, collagen and proteoglycan in plaques were also significantly increased in AdPPARgamma1 and AdPPARgamma1 + RO groups. Upregulation of PPARgamma, SM-actin, TIMP-1 antigen activity and downregulation of MOMA-2, MMP-9, CD40/CD40L and TF antigen activity in AdPPARgamma1 and most significantly in AdPPARgamma1 + RO group were observed (P < 0.05).


CONCLUSIONS
Anti-atherosclerotic effects of PPARgamma1 gene transfer in ApoE-knock out mice could be enhanced by PPARgamma agonist rosiglitazone.
Hu
Qin
Q
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital, Shandong University, Jinan 250012, China.
Zhang
Yun
Y
Zhang
Xian-Jun
XJ
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics*; D018014:Gene Transfer Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014162:Transfection
D001057:Apolipoproteins E; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones; D000077154:Rosiglitazone