Osteopontin: At the cross-roads of myocyte survival and myocardial function

Heart failure represents a major cause of morbidity and mortality in Western society. Cardiac myocyte loss due to apoptosis plays a significant role in the progression of heart failure. The extracellular matrix (ECM) maintains the structural integrity of the heart and allows the transmission of electrical and mechanical signals during cardiac contraction and relaxation. Matricellular proteins, a class of non-structural ECM proteins, play a significant role in ECM homeostasis and intracellular signaling via their interactions with cell surface receptors, structural proteins, and/or soluble extracellular factors such as growth factors and cytokines. Osteopontin (OPN), also called cytokine Eta-1, is a member of the matricellular protein family. The normal heart expresses low levels of OPN. However, OPN expression increases markedly under a variety of pathophysiological conditions of the heart. Many human and transgenic mouse studies provide evidence that increased OPN expression, specifically in myocytes, is associated with increased myocyte apoptosis and myocardial dysfunction. This review summarizes OPN expression in the heart, and its role in myocyte apoptosis and myocardial function.