Syndecan 4 signaling is required for exercise-induced cardiac hypertrophy.

Cardiac hypertrophy can be broadly classified as either physiological or pathological. Physiological stimulus such as exercise cause adaptive cardiac hypertrophy and normal heart function. Pathological stimulus such as hypertension and aortic valvular stenosis cause maladaptive cardiac remodeling and ultimately heart failure. Syndecan 4(synd4) is a transmembrane proteoglycan and identified to be involved in cardiac adaptation after injury. Whether it takes part in physiological cardiac hypertrophy is unclear. We observed up-regulation of synd4 in exercise-induced hypertrophic myocardium. To evaluate the role of synd4 in the physiological form of cardiac hypertrophy, mice lacking synd4 (synd4-/-) were exercised by swimming for 4 weeks. Ultrasonic cardiogram (UCG) and histological analysis revealed that swimming-induced the hypertrophic phenotype was blunted in syn4-/- compared with WT mice. The swimming-induced activation of Akt, a key molecule in physiological hypertrophy was also decreased than that seen in wild-type controls. In cultured cardiomyocytes, synd4 over expression could induce cell enlargement, protein synthesis, and distinct physiological molecular alternation. Akt activation was also observed in synd4 over expressed cardiomyocytes. Furthermore inhibition of Protein kinase C (PKC) prevented the synd4 induced hypertrophic phenotype and Akt phosphorylation. This study identified an essential role of synd4 in mediation of physiological cardiac hypertrophy.