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.
Ogihara
T
T
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Morita
R
R
Morimoto
S
S
Imanaka
S
S
Fukuo
K
K
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001055:Apolipoproteins B / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005260:Female; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D000584:Amiloride; D015544:Inositol 1,4,5-Trisphosphate; D004247:DNA; D012964:Sodium; D002118:Calcium