Endothelial HSPA12B Exerts Protection Against Sepsis-Induced Severe Cardiomyopathy via Suppression of Adhesion Molecule Expression by miR-126.

Heat shock protein A12B is predominately expressed in endothelial cells (ECs) and has been reported to protect against cardiac dysfunction from endotoxemia or myocardial infarction. This study investigated the mechanisms by which endothelial protects polymicrobial sepsis-induced cardiomyopathy. Wild-type (WT) and endothelial Hduanyu184212B knockout mice were subjected to polymicrobial sepsis induced by cecal ligation and puncture (CLP). Cecal ligation and puncture sepsis accelerated mortality and caused severe cardiac dysfunction in mice compared with WT septic mice. The levels of adhesion molecules and the infiltrated immune cells in the myocardium of Hduanyu184212B^-/- septic mice were markedly greater than in WT septic mice. The levels of microRNA-126 (miR-126), which targets adhesion molecules, in serum exosomes from Hduanyu184212B^-/- septic mice were significantly lower than in WT septic mice. Transfection of ECs with adenovirus expressing Hduanyu184212B significantly increased miR-126 levels. Increased miR-126 levels in ECs prevented LPS-stimulated expression of adhesion molecules. In vivo delivery of miR-126 carried by exosomes into the myocardium of Hduanyu184212B^-/- mice significantly attenuated CLP sepsis increased levels of adhesion molecules, and improved CLP sepsis-induced cardiac dysfunction. The data suggest that Hduanyu184212B protects against sepsis-induced severe cardiomyopathy via regulating miR-126 expression which targets adhesion molecules, thus decreasing the accumulation of immune cells in the myocardium.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}