Benzo[a]pyrene induces expression of matrix metalloproteinases and cell migration and invasion of vascular smooth muscle cells.
Benzo[a]pyrene (B[a]P) has been shown to accelerate atherosclerosis development in animal models. However, the mechanisms that B[a]P induces atherogenesis are unclear. Abnormal migration and invasion of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic lesions. In this article, we demonstrated that B[a]P promoted the migration and invasion of rat VSMCs. B[a]P increased the mRNA levels of matrix metalloproteinase (MMP) 1, 2, 3, and 9. The MMPs inhibitor GM6001 inhibited B[a]P-induced invasion of VSMCs. Among the MMPs mentioned above, MMP-3 had the maximal induction. Mechanistic studies indicate that B[a]P-induced transcriptional activation of MMP-3 is not mediated by AP-1, NF-kappaB. B[a]P-induced expression of MMPs was attenuated by alpha-naphthoflavone, the aryl hydrocarbon receptor antagonist. In addition, alpha-naphthoflavone inhibited B[a]P-induced migration and invasion of VSMCs. These results suggest that the aryl hydrocarbon receptor plays an important role in B[a]P-induced expression of MMPs and migration and invasion of VSMC. Our findings may reveal a novel role of B[a]P in inducing atherogenesis.
Meng
Dan
D
The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Tai-Yuan Road, Shanghai 200031, PR China.
Lv
Dan-Dan
DD
Zhuang
Xuliang
X
Sun
Heng
H
Fan
Li
L
Shi
Xiang-Lin
XL
Fang
Jing
J
D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects*
D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; D020782:Matrix Metalloproteinases