microRNA-135a-5p regulates NOD-like receptor family pyrin domain containing 3 inflammasome-mediated hypertensive cardiac inflammation and fibrosis via thioredoxin-interacting protein.

Hypertension is a severe public health problem that induces cardiac injury with alterations of gene expressions. The current study sought to evaluate the mechanism of microRNA(miR)-135a-5p in NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediation of cardiac inflammation and hypertensive cardiac fibrosis. Firstly, hypertensive mouse models were established using angiotensin II (Ang II), followed by miR-135a-5p agomir treatment. Subsequently, mouse blood pressure and basic cardiac function indexes, histopathological changes, and cardiac fibrosis were all determined, in addition to detection of factors related to inflammation and fibrosis. Additionally, mice cardiac fibroblasts (CFs) were isolated and treated with Ang II. The binding relationship of miR-135a-5p and thioredoxin-interacting protein (TXNIP) was predicted and testified, while the interaction of TXNIP and NLRP3 was detected by means of a co-immunoprecipitation assay. It was found that miR-135a-5p was poorly-expressed in Ang II-treated mice and further exerted cardioprotective effects against hypertensive heart diseases. Moreover, over-expression of miR-135a-5p resulted in inhibition of inflammatory infiltration and almost eliminated cardiac fibrosis, as evidenced by decreased Collagen (COL)-I, COL-III, a-smooth muscle actin, NLRP3, tumor necrosis factor-α, and interleukin-6. Mechanically, miR-135a-5p inhibited TXNIP expression to block the binding of TXNIP and NLRP3. On the other hand, TXNIP up-regulation reversed the protective role of miR-135a-5p over-expression in CFs. Collectively, our findings indicated that miR-135a-5p over-expression inhibited TXNIP expression to block the binding of TXNIP and NLRP3, thereby alleviating hypertensive cardiac inflammation and fibrosis.