Angiotensin II induces matrix metalloproteinase-9 expression via a nuclear factor-kappaB-dependent pathway in vascular smooth muscle cells.
Angiotensin II (AngII) is widely recognized as a critical regulator of the development of atherosclerosis. Matrix metalloproteinases (MMPs) are thought to participate in plaque destabilization through degradation of the extracellular matrix. In the present study, we investigated the potential mechanism of AngII-induced MMP-9 expression in vascular smooth muscle cells (VSMC). AngII upregulated the expression of MMP-9 significantly in VSMC obtained from rat aorta. RNAi-mediated knockdown of p65 and losartan, an inhibitor of AngII receptors subtype-1 (AT1), could abolish AngII-induced MMP-9 expression. In addition, AngII induced the NF-kappaB binding activity via AT1 and AT2 receptors in VSMC, and AngII-induced activation of NF-kappaB is not associated with significant downregulation of IkappaB. In summary, this study demonstrates that AngII stimulates NF-kappaB nuclear translocation in VSMC via AT1 and AT2. AngII increases the expression of MMP-9 in VSMC, and AT1 and NF-kappaB pathways have an important role in this response.
Guo
Rui-wei
RW
Department of Cardiology, Kunming General Hospital of Chengdu Military Area, Yunnan, 650032, China.
Yang
Li-xia
LX
Wang
Hong
H
Liu
Bei
B
Wang
Lei
L
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015870:Gene Expression; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation
D016328:NF-kappa B; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D020780:Matrix Metalloproteinase 9