Intracellular signal transduction evoked by low-density lipoprotein in vascular smooth muscle cells

Low-density lipoprotein (LDL) is a well-known causal factor in the development of arteriosclerosis. In the present study, we evaluated LDL-evoked cellular signal transduction in cultured rat vascular smooth muscle cells (VSMC). The addition of LDL at concentrations of more than 50 ng/ml, and apolipoprotein B (Apo-B) at more than 5 ng/ml, induced rapid but transient increases in the inositol 1,4,5-trisphosphate (InsP3) level, and caused rapid phasic and subsequent tonic increases in cytosolic free Ca2+ concentration [( Ca2+]i) in a dose-dependent manner in VSMC. LDL and Apo-B also caused transient acidification followed by Na(+)-dependent and amiloride-sensitive alkalization of the cells due to stimulation of a Na+/H+ exchanger. The enhancement of thymidine incorporation induced by the addition of LDL correlated well with the degree of increment of [Ca2+]i increases by the lipoprotein. These results suggest that an increase in [Ca2+]i mediated by InsP3 and intracellular alkalization may function as an important signal for enhanced DNA synthesis induced by LDL in VSMC.