Interactions between cultured bovine arterial endothelial and smooth muscle cells; effects of modulated low density lipoproteins on cell proliferation and prostacyclin release

Abstract

We exposed bovine aortic endothelial cells in culture to native LDL (n-LDL) and LDL modulated by dimethylsulfoxide (DMSO-LDL), dimethylsulfoxide-soluble particles from cigarette smoke (DSP-LDL) or Cu²⁺ (Cu²⁺-LDL) to explore the hypothesis that these LDL-forms might influence interactions between endothelial and smooth muscle cells. It was shown that 3H-thymidine incorporation into endothelial cells was decreased by DMSO-LDL, DSP-LDL and Cu²⁺-LDL compared to n-LDL, while it was higher by DSP-LDL compared to its control i.e. DMSO-LDL. These effects could be transferred by conditioned medium to smooth muscle cell cultures. DSP-LDL or Cu²⁺-LDL decreased total cellular protein of endothelial cells.

Initial (15min) prostacyclin release from endothelial cells was increased by all LDL preparations compared to medium without LDL, most pronounced for Cu²⁺-LDL. If n-LDL was control, only Cu²⁺-LDL significantly increased the release of prostacyclin during 15min and during 24 h. The release of prostacyclin assayed after 24 h was depressed by DSP-LDL compared to DMSO-LDL. This study demonstrated that interactions between endothelial and smooth muscle cells could be influenced by LDL treated by dimethylsulfoxide-soluble particles from cigarette smoke or by Cu²⁺, and their effects were not similar. DSP-LDL, in contrast to Cu²⁺-LDL, significantly decreased the release of prostacyclin by endothelial cells after 24 h incubations and via endothelial cell conditioned medium stimulated smooth muscle cell proliferation judged by increased 3H-thymidine incorporation. The results might be of relevance for atherogenesis.

Key Words:

• atherosclerosis
• endothelial cells
• modulated LDL
• proliferation
• prostacyclin
• smooth muscle cells