Dec1 deficiency protects the heart from fibrosis, inflammation, and myocardial cell apoptosis in a mouse model of cardiac hypertrophy.

Cardiac inflammation and fibrosis triggered by left ventricular pressure overload are the major causes of heart dysfunction. Differentiated embryonic chondrocyte gene 1 (Dec1) is a basic helix-loop-helix transcription factor that is comprehensively involved in inflammation and tissue fibrosis, but its role in cardiac hypertrophy remains unclear. This study explored the effects of Dec1 on cardiac fibrosis, inflammation, and apoptosis in hypertrophic conditions. Transverse aortic constriction (TAC) was performed to induce cardiac hypertrophy in wild-type (WT) mice and in Dec1 knock out (KO) mice for 4 weeks. Using the TAC mouse model, prominent differences in cardiac hypertrophy at the morphological, functional, and molecular levels were delineated by Masson's Trichrome and TUNEL staining, immunohistochemistry, RT-PCR and Western Blot. DNA microarray and microRNA (miRNA) array analyses were carried out to identify gene and miRNA expression patterns. Dec1KO mice exhibited a more severe hypertrophic heart, whereas WT mice showed a more pronounced perivascular fibrosis after TAC at 4 weeks. The Dec1 deficiency promoted M2 phenotype macrophages. Dec1KO TAC mice showed fewer apoptotic cells than WT TAC mice. APEX1, WNT16, FGF10 and MMP-10 were differentially expressed according to DNA microarray analysis and expression levels of those genes and the corresponding miRNAs (miR-295, miR-200 b, miR-130a, miR-92a) showed the same trends. Furthermore, luciferase reporter assay confirmed that FGF10 is the direct target gene of miR-130. In conclusion, a Dec1 deficiency protects the heart from perivascular fibrosis, regulates M1/M2 macrophage polarization and reduces cell apoptosis, which may provide a novel insight for the treatment of cardiac hypertrophy.