The transcriptional regulation of calcium induced cell death in heart

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Recent studies demonstrated that the osteopontin (OPN), an acid phosphoprotein plays pivotal roles in cardiac hypertrophy and failure. An osteogenic transcription factor Runx2 regulates the expression of OPN in osteoblasts. In the present study, we attempted to examine the pathological role of Runx2 in cardiac hypertrophy and failure. We generated transgenic mice (TG) overexpressing Runx2. Two TG lines (low and high) were obtained and high-expressing TG (HE-TG) showed cardiac hypertrophy and premature death within 8 weeks of age. In addition, HE-TG mice demonstrated decreased fractional shortening assessed by echocardiography. In response to pressure overload, low expressing TG (LE-TG) demonstrated higher mortality and enhanced cardiac hypertrophic response after TAC. In conclusion, targeted expression of Runx2 in heart mediates cardiac dysfunction and hypertrophy in mice. Thus, Runx2 could be a novel therapeutic target for heart failure.