title: Cholesterol enhances platelet-derived growth factor-BB-induced [Ca2+]i and DNA synthesis in rat aortic smooth muscle cells.
abstract: In the present study, we describe possible mechanisms by which hypercholesterolemia may contribute to the development of cardiovascular diseases. Treatment of rat aortic smooth muscle cells for 20 hours with cholesterol-rich liposomes (500 micrograms/mL cholesterol, 100 micrograms/mL low-density lipoprotein) resulted in a 76 +/- 12% increase in total cholesterol content. The effects of cholesterol enrichment were examined by determination of changes in cell membrane fluidity. Fluidity of the cholesterol-enriched cell membranes was decreased at all temperatures between 15 degrees C and 40 degrees C. Changes in membrane fluidity in whole cell membranes represented changes in fluidity of microsomal membranes isolated by Percoll gradient ultracentrifugation. The basal [Ca2+]i and the maximal platelet-derived growth factor (PDGF)-BB-induced [Ca2+]i was elevated by 30% and 90% in cholesterol-enriched cells, respectively. In contrast, the resting pH, and the PDGF-BB-induced stimulation of the Na+/H+ exchange were not affected in cholesterol-enriched cells. The effect of PDGF-BB on [3H]thymidine incorporation in cholesterol-enriched cells was elevated by 40% in comparison with untreated cells. Our findings show that cellular cholesterol may be involved in the development of vascular diseases via modulation of the PDGF-induced increase in [Ca2+]i and DNA synthesis in vascular smooth muscle cells.
authors.affiliation: Medizinische Universitäts-Poliklinik, Bonn, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Sachinidis
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: A A
authors.initials: AA
authors.lastname: Weber
authors.forename: C
authors.initials: C
authors.lastname: Seul
authors.forename: V
authors.initials: V
authors.lastname: Harth
authors.forename: S
authors.initials: S
authors.lastname: Seewald
authors.forename: Y
authors.initials: Y
authors.lastname: Ko
authors.forename: H
authors.initials: H
authors.lastname: Vetter
mesh_terms: D000818:Animals; D000077214:Becaplermin; D002118:Calcium / Q000378:metabolism*; D002784:Cholesterol / Q000494:pharmacology*; D008078:Cholesterol, LDL / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D004357:Drug Synergism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008081:Liposomes / Q000494:pharmacology; D008560:Membrane Fluidity / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D008078:Cholesterol, LDL; D008081:Liposomes; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D004247:DNA; D002784:Cholesterol; D002118:Calcium