Depletion of Kindlin-2 induces cardiac dysfunction in mice.

Kindlin-2, a member of the Kindlin family focal adhesion proteins, plays an important role in cardiac development. It is known that defects in the Z-disc proteins lead to hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM). Our previous investigation showed that Kindlin-2 is mainly localized at the Z-disc and depletion of Kindlin-2 disrupts the structure of the Z-Disc. Here, we reported that depletion of Kindlin-2 leads to the disordered myocardial fibers, fractured and vacuolar degeneration in myocardial fibers. Interestingly, depletion of Kindlin-2 in mice induced cardiac myocyte hypertrophy and increased the heart weight. Furthermore, decreased expression of Kindlin-2 led to cardiac dysfunction and also markedly impairs systolic function. Our data indicated that Kindlin-2 not only maintains the cardiac structure but also is required for cardiac function.