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(Hypertension. 1997;29:326.)
© 1997 American Heart Association, Inc.

Arthur C. Corcoran Memorial Lecture

Cholesterol Enhances Platelet-Derived Growth Factor-BB-Induced [Ca²⁺]_i and DNA Synthesis in Rat Aortic Smooth Muscle Cells

Agapios Sachinidis; Min Liu; Artur-Aron Weber; Claudia Seul; Volker Harth; Stefan Seewald; Yon Ko; Hans Vetter

From the Medizinische Universitäts-Poliklinik, Bonn, Germany.

Correspondence to PD Dr A. Sachinidis, Medizinische Universitäts-Poliklinik, Wilhelmstr 35–37, 53111 Bonn, Germany

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 µg/mL cholesterol, 100 µg/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°C and 40°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_i 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.

Key Words: cholesterol • vascular smooth muscle cells • platelet-derived growth factor

Abbreviations: DMEM = Dulbecco’s modified Eagle’s medium • PC = dipalmitoylphosphatidylcholine • PDGF = platelet-derived growth factor • VSMC = vascular smooth muscle cell(s)

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