Nature of aortic smooth muscle cellular activity induced by cholesterol incorporation through an LDL-receptor-independent pathway: preventive role of trifluoperazine on such activity.
The present study was addressed to understand two specific issues: (a) whether atherogenic activity of smooth muscle cells could be initiated by incorporating cholesterol within their membranes through a LDL-receptor-independent pathway; and (b) whether trifluoperazine, which we had recently shown to prevent the cholesterol-induced atherogenesis in an experimental animal model system, could prevent such activity of these cells induced by cholesterol in vitro. The results of such a study revealed that trifluoperazine could prevent the cholesterol-induced stimulation of (a) DNA synthesis, (b) cholesterol synthesis, (c) intracellular cGMP levels, (d) intracellular free and esterified cholesterol accumulation, and (e) collagen secretion. Furthermore, the drug caused stimulation of cholesterol-induced suppression of LDL-receptor synthesis. On this basis, we suggest that acquisition of cholesterol by smooth muscle cells through the LDL-receptor-independent pathway may be the fundamental process responsible for atherogenic activity of these cells and that the drug trifluoperazine has the inherent capacity to prevent the membrane-cholesterol-modulated atherogenic activity of smooth muscle cells in vitro.
Mehta
U
U
Experimental Medicine Department, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
Kaul
D
D
D000818:Animals; D001011:Aorta; D001161:Arteriosclerosis / Q000517:prevention & control; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism* / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D011817:Rabbits; D011973:Receptors, LDL / Q000502:physiology*; D014268:Trifluoperazine / Q000494:pharmacology / Q000627:therapeutic use*
D011973:Receptors, LDL; D014268:Trifluoperazine; D003094:Collagen; D002784:Cholesterol; D006152:Cyclic GMP