- 作者: Ashwani K Khanna
- 作者服務機構: Department of Medicine (Cardiology), University of Maryland, Baltimore, USA
- 中文摘要: --
- 英文摘要:
Cyclin kinase inhibitor p21 is one of the most potent inhibitors of aortic smooth muscle cell
proliferation, a key mediator of atherosclerosis. This study tests if p2l deficiency will result in
severe atherosclerosis in a mouse model. p21-/- and strain matched wild type mice were fed with
high fat diet for 21 weeks. Analysis for biochemical parameters (cholesterol, triglycerides) in
serum and mRNA expression of CD36, HO-1, TGF-β, IFN-γ, TNF-α, PPAR-γ and NADPH
oxidase components (p22phox, NOX-1 and Rac-1) was performed in aortic tissues by Real Time
PCR. p21-/- mice gained significantly (p<0.01) more weight than wild type mice, triglycerides
(p<0.05) and cholesterol levels (p<0.01) were more pronounced in the sera of p21-/- compared to
wild type mice fed with high fat diet. High fat diet resulted in significantly decreased TGF-β
(p<0.02), HO-l (p<0.02) and increased CD36 (p<0.03) mRNA expression in aortic tissues of
p21-/- mice compared to animal fed with regular diet. IFN-γ mRNA expression (235 ± 11 folds)
increased significantly in high fat diet fed p21-/- mice and a multifold modulation of PPAR-
γ (136 ± 7), p22phox, NOX-1 and Rac-1 (15-35-folds) mRNA in aortic tissues from p21-/- mice
compared to the wild type mice. Severity of atherosclerotic lesions was significantly higher in
p21-/- compared to wild type ice. The results demonstrate that the deficiency of p21 leads to
altered expression of pro-atherogenic genes, and severe atherosclerosis in mice fed with high fat
diet. This opens the possibility of p21 protein as a therapeutic tool to control progression of
atherosclerosis. - 中文關鍵字: --
- 英文關鍵字: --