Effect of hypoxia and hypoxia/reoxygenation on proteoglycan metabolism by vascular smooth muscle cells

• Published in: Atherosclerosis 1999-03, Vol.143 (1), p.135-144
• Main Authors: Figueroa, Julio E., Tao, Zhuo, Sarphie, Theodore G., Smart, Frank W., Glancy, D.Luke, Vijayagopal, Parakat
• Format: Article
• Language: English
• Subjects: Aorta; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Hypoxia; Cells, Cultured; Humans; Hypoxia/reoxygenation; LDL-binding; Lipoproteins, LDL - metabolism; Medical sciences; Microscopy, Electron, Scanning; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - ultrastructure; Oxygen - physiology; Protein Biosynthesis; Proteoglycan synthesis; Proteoglycans - biosynthesis; Proteoglycans - metabolism; Smooth muscle cells
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(98)00292-5

Hypoxia and hypoxia/reoxygenation are known to affect vascular smooth muscle cell physiology. In this study, we first investigated proteoglycan synthesis by human aortic smooth muscle cells exposed to normoxia, hypoxia, or hypoxia/reoxygenation. We then compared the newly synthesized proteoglycans from normoxic and hypoxic-reoxygenation cultures for their ability to bind low density lipoprotein (LDL). Confluent smooth muscle cells under normoxia, hypoxia, or hypoxia/reoxygenation were pulsed with [ 35S]sulfate, and secreted and cell-associated proteoglycans were analyzed. Secreted proteoglycans in cultures exposed to hypoxia (4 h)/reoxygenation (19 h) increased 28% over those of cells continuously exposed to normoxia. Cell-associated proteoglycans did not differ significantly between the two groups. In contrast, hypoxia (4 h) followed by a 30-min reoxygenation produced a 37% decrease in newly synthesized proteoglycans. Hypoxia alone also resulted in a 24% decrease in secreted proteoglycans and a 20% decrease in cell-associated proteoglycans. Proteoglycans newly synthesized by smooth muscle cells exposed to normoxia and hypoxia/reoxygenation did not differ in their charge densities and molecular size but did differ in glycosaminoglycan composition. Exposure of smooth muscle cells to hypoxia/reoxygenation produced a 60% increase in a proteoglycan subfraction that bound LDL with very high affinity. The incorporation of [ 3H]leucine into total cellular protein decreased significantly following exposure of smooth muscle cells to hypoxia as well as hypoxia/reoxygenation. These results indicate that hypoxia and hypoxia/reoxygenation cause major alterations in proteoglycan metabolism by vascular smooth muscle cells.