To investigate the role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in myocardial fibrosis.

During in vivo experiments using NLRP3-knockout and wild-type mice, myocardial fibrosis model was constructed via intraperitoneal injection of isoproterenol (ISO) . Masson staining was used to examine the cardiac fibrosis in mice; immunohistochemical staining with CD31 was used to label the cardiovascular density; Western blotting was used to detect the changes in expression of markers related to endothelial cells and mesenchymal cells. During the in vitro experiments, human umbilical vein endothelial cells (HUVEC) and small interfering RNA were used for silencing of NPRP3. Immunofluorescence co-staining with CD31 and a-SMA were used to examine the endothelial-mesenchymal transition.

NLRP3 knockout significantly reduced the ISO-induced myocardial collagen deposition and blood vessel density (P<0.05) , increase the expression of endothelial cell marker CD34 (P<0.05) , and reduce the expression of mesenchymal cell marker a-SMA and Vimentin (P<0.05) . CD31 and a-SMA immunofluorescence co-staining of HUVECs showed that TGF-β stimulation significantly reduced the expression of endothelial cell marker CD31 and increased the expression of mesenchymal cell marker a-SMA. Silencing of NLRP3 was able to significantly reverse such a change in phenotype (P<0.05) .

NLRP3 knockout may attenuate ISO-induced myocardial fibrosis by suppressing endothelial-mesenchymal transition (EndMT) .

Fibrosis; Heart failure; NLRP3; Isoproterenol