NLRP3 gene deletion attenuated Angiotensin II-induced vascular smooth muscle cell phenotypic transformation, proliferation, vascular remodeling, and hypertension in mice.
Does NLRP3 gene deletion prevent Angiotensin II-induced vascular smooth muscle cell phenotypic transformation and vascular remodeling?
NLRP3 gene deletion protects against Angiotensin II-induced vascular remodeling and hypertension by preventing vascular smooth muscle cell phenotypic transformation.
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.
Ren et al. (Sun,) conducted a other in Hypertension and vascular remodeling. NLRP3 gene deletion vs. Wild-type (WT) mice was evaluated on NLRP3 inflammasome activation, phenotypic transformation, proliferation, vascular remodeling, and hypertension. NLRP3 gene deletion attenuated Angiotensin II-induced vascular smooth muscle cell phenotypic transformation, proliferation, vascular remodeling, and hypertension in mice.