Cardiomyocyte-Specific Deletion of the Vitamin D Receptor Gene Results in Cardiac Hypertrophy

• DOI: 10.1161/circulationaha.111.032680
• Publication Date: 2011-09-27T06:27:31Z
• Authors: Songcang Chen; Christopher S. Law; Christopher L. Gr...; Keith Olsen; Ting-Ting Hong; Yan Zhang; Yerem Yeghiazarians; David G. Gardner
• Keywords: Mice, Inbred C57BL; Mice, Knockout; Mice; Mice, 129 Strain; Gene Targeting; Animals; Receptors, Calcitriol; Cardiomegaly; Myocytes, Cardiac; Gene Deletion; 3. Good health

Background— A variety of studies carried out using either human subjects or laboratory animals suggest that vitamin D and its analogues possess important beneficial activity in the cardiovascular system. Using Cre-Lox technology we have selectively deleted receptor (VDR) gene cardiac myocyte an effort to better understand role regulating structure function. Methods Results— Targeted deletion exon 4 coding sequence VDR resulted increase size left ventricular weight/body weight versus controls both at baseline following a 7-day infusion isoproterenol. There was no interstitial fibrosis. These knockout mice demonstrated reduction end-diastolic end-systolic volume by echocardiography, activation fetal program (ie, increased atrial natriuretic peptide alpha skeletal actin expression), expression modulatory calcineurin inhibitory protein 1 (MCIP1), direct downstream target calcineurin/nuclear factor activated T cell signaling. Treatment neonatal cardiomyocytes with 1,25-dihydroxyvitamin partially reduced isoproterenol-induced MCIP1 mRNA levels promoter activity. Conclusions— Collectively, these demonstrate D-VDR signaling system possesses direct, antihypertrophic heart. This appears involve, least part, suppression prohypertrophic calcineurin/NFAT/MCIP1 pathway. identify potential mechanism account for reported effects