NLRP3 Gene Deletion Attenuates Angiotensin II-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells and Vascular Remodeling

作者：Ren, Xing-Sheng; Tong, Ying; Ling, Li; Chen, Dan; Sun, Hai-Jian; Zhou, Hong; Qi, Xiao-Hong; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing^*

来源：Cellular Physiology and Biochemistry, 2017, 44(6): 2269-2280.

DOI：10.1159/000486061

• Nlrp3 inflammasome
• Angiotensin
• Vascular remodeling
• Vascular smooth muscle cells
• Phenotypic transformation
• Hypertension

Background/Aims: Angiotensin (Ang) II plays vital roles in vascular inflammation and remodeling in hypertension. Phenotypic transformation of vascular smooth muscle cells (VSMCs) is a major initiating factor for vascular remodeling. The present study was designed to determine the roles of NLRP3 inflammasome activation in Ang IIinduced VSMC phenotypic transformation and vascular remodeling in hypertension. Methods: Primary VSMCs from the aorta of NLRP3 knockout (NLRP3(-/-)) mice and wildtype (WT) mice were treated with Ang II for 24 h. Subcutaneous infusion of Ang II via osmotic minipump for 2 weeks was used to induce vascular remodeling and hypertension in WT and NLRP3(-/-) mice. Results: NLRP3 gene deletion attenuates Ang IIinduced NLRP3 inflammasome activation, phenotypic transformation from a contractile phenotype to a synthetic phenotype and proliferation in primary mice VSMCs. Ang IIinduced hypertension and vascular remodeling in WT mice were attenuated in NLRP3(-/-) mice. Furthermore, Ang IIinduced NLRP3 inflammasome activation, phenotypic transformation and proliferating cell nuclear antigen (PCNA) upregulation were inhibited in the media of aorta of NLRP3(-/-) mice. Conclusions: NLRP3 inflammasome activation contributes to Ang IIinduced VSMC phenotypic transformation and proliferation as well as vascular remodeling and hypertension.

• 出版日期2017
• 单位南京医科大学; 西安交通大学