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

Abstract

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 II-induced VSMC phenotypic transformation and vascular remodeling in hypertension.

METHODS:

Primary VSMCs from the aorta of NLRP3 knockout (NLRP3-/-) mice and wild-type (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 II-induced NLRP3 inflammasome activation, phenotypic transformation from a contractile phenotype to a synthetic phenotype and proliferation in primary mice VSMCs. Ang II-induced hypertension and vascular remodeling in WT mice were attenuated in NLRP3-/- mice. Furthermore, Ang II-induced 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 II-induced VSMC phenotypic transformation and proliferation as well as vascular remodeling and hypertension.

• Authors: Xing-Sheng Ren, Ying Tong, Li Ling, Dan Chen, Hai-Jian Sun, Hong Zhou, Xiao-Hong Qi, Qi Chen, Yue-Hua Li, Yu-Ming Kang, Guo-Qing Zhu
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 44 Issue 6 Pg. 2269-2280 ( 2017) ISSN: 1421-9778 [Electronic] Germany
• PMID: 29262411 (Publication Type: Journal Article)
• Copyright: © 2017 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Angiotensin II

Topics

• Angiotensin II (metabolism)
• Animals
• Blood Pressure
• Cells, Cultured
• Gene Deletion
• Hypertension (genetics, metabolism, physiopathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Muscle, Smooth, Vascular (metabolism, physiopathology)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Vascular Remodeling