Role for the PIP₂-binding protein myristoylated alanine-rich C-kinase substrate in vascular tissue: A novel therapeutic target for cardiovascular disease

In vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs), phosphatidylinositol 4,5-bisphosphate (PIP₂) acts as a substrate for phospholipase C (PLC)- and phosphoinositol 3-kinase (PI3K)-mediated signaling pathways and an unmodified ligand at ion channels and other macromolecules, which are key processes in the regulation of cell physiological and pathological phenotypes. It is envisaged that these distinct roles of PIP₂ are achieved by PIP₂-binding proteins, which act as PIP₂ buffers to produce discrete pools of PIP₂ that permits targeted release within the cell. This review discusses evidence for the expression, cell distribution, and role of myristoylated alanine-rich C-kinase substrate (MARCKS), a PIP₂-binding protein, in cellular signaling and function of VSMCs. The review indicates the possibilities for MARCKS as a therapeutic target for vascular disease involving dysfunctional cell proliferation and migration, endothelial barrier permeability, and vascular contractility such as atherosclerosis, systemic and pulmonary hypertension, and sepsis.