Gene expression analysis in heart from wild-type or ADAM12 knockout mice under heart failure condition.

To investigated global changes caused by pressure overload-induced heart failure in ADAM12 knockout mice using a microarray analysis. A disintegrin and metalloproteinase (ADAM) 12 is has long been considered to promote cardiac dysfunction based on according to the finding report that a small molecule ADAM12 inhibitor, KB-R7785 ameliorated cardiac function in a transverse aortic constriction (TAC) model by inhibiting the through inhibition of proteolytic activation of HB-EGF signaling. HoweverOn the other hand, this compound has poor selectivity for ADAM12, and the role of ADAM12 inon cardiac dysfunction has not yet been investigated usingby genetic loss-of-function mice. Anoperation. ADAM12 deficiency resulted in significantly more expanded cardiac fibrosis accompanied byaccompanying with increased collagen-related gene expression in their failing hearts. The results of a genome-wide transcriptional analysis suggested a strongly enhanced highly elevated focal adhesion- and fibrosis-related signaling pathway in ADAM12 knockout hearts. The present results study revealed that the loss of ADAM12 enhanced focal adhesion and canonical TGF-β signaling by regulating the abundance of the integrin β1 and TGF-β receptors. To evaluate heart RNAs two weeks after TAC surgery in order to observe characteristic changes in the genes of signaling elements. Three biological replicates from each genotypes were used. The analysis was performed using Affymetrix Mouse Clariom D (MTA 1.0) array.