Syndecan-4 deficiency accelerates the transition from compensated hypertrophy to heart failure following pressure overload.

Increasing evidence suggests that a mismatch between angiogenesis and myocardial growth contributes to the transition from adaptive cardiac hypertrophy to heart failure following pressure overload. Syndecan-4 is a transmembrane proteoglycan that binds to growth factors and extracellular matrix proteins and is critical in focal adhesion formation. However, its effects on coronary angiogenesis during pressure overload-induced heart failure have not been studied. Here, we hypothesize that syndecan-4 modulates cardiac remodeling in response to pressure overload through its ability to regulate adaptive angiogenesis. Syndecan-4 knockout (syndecan-4 KO) and wild-type (WT) mice were subjected to pressure overload induced by transverse aortic constriction (TAC). Syndecan-4 KO mice exhibited reduced capillary density, attenuated cardiomyocyte size, and worsened left ventricular cardiac function after TAC surgery compared with WT mice. Moreover, syndecan-4 KO mice showed a significant decrease in protein kinase C alpha expression. Our data suggest that syndecan-4 is essential for the compensated hypertrophy and the maintenance of cardiac function during the process of heart failure following pressure overload.