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.

NR4A1 Promotes Diabetic Nephropathy by Activating Mff-Mediated Mitochondrial Fission and Suppressing Parkin-Mediated Mitophagy

“…Chronic hyperglycemia has also been acknowledged to play a decisive role in the development of DN [3]. At the molecular level, several of the biological processes affected by high glucose, including glomerular apoptosis, interstitial fibrosis, and metabolic reprogramming [4,5], are tightly linked to mitochondrial homeostasis, and each of these processes is strongly affected by alterations in the balance of mitochondrial dynamics [6,7], including mitochondrial fission and mitophagy [8]. These facts indicate that changes in mitochondrial morphology may underlie many of the phenotypes that control the pathological progression of DN.…”

Cathepsin B-Mediated NLRP3 Inflammasome Formation and Activation in Angiotensin II -Induced Hypertensive Mice: Role of Macrophage Digestion Dysfunction

“…As a pattern recognition receptor, NLRP3 is upregulated by stimulation with pathogen-associated molecular patterns (PAMPs) [4], which are recruited by the adapter protein apoptosisassociated speck-like protein containing CARD (ASC), and then converts pro-caspase-1 into cle-caspase-1 (cleaved form) [5]. NLRP3 inflammasome activation transforms proinflammatory cytokines such as interleukin (IL)-1β and IL-18 from their immature "pro" forms to their active forms, which have different effects in different cell types, including phenotypic transformation, cell pyroptosis, and cell membrane permeability [6][7][8]. In macrophages, NLRP3 inflammasome activation is critical in the formation of foam cells and other atherosclerotic lesions in response to proatherogenic stimuli such as cholesterol crystals [9,10].…”

Mammalian STE20-Like Kinase 1 Deletion Alleviates Renal Ischaemia-Reperfusion Injury via Modulating Mitophagy and the AMPK-YAP Signalling Pathway

“…Unfortunately, although reperfusion restores blood flow to infarcted kidney tissues, the reperfusion itself also induces additional damage to the kidney tissue, which is referred to as ischemia-reperfusion (I/R) injury [2, 3]. In spite of the extensive research that has been carried out over the past six decades in the field of renal IR injury [4, 5], the pathogenesis of reperfusion-mediated kidney damage is poorly understood [6]. …”