© 2000 American Heart Association, Inc.
Integrative Physiology |
Phenotypic and Functional Changes in Regenerated Porcine Coronary Endothelial Cells
Increased Uptake of Modified LDL and Reduced Production of NO
From the Institut de Recherches Servier, Suresnes, France.
Correspondence to Paul M. Vanhoutte, Institut de Recherches Internationales Servier, 6 Place des Pléiades, 92415 Courbevoie, France. E-mail vanhoutt{at}servier.fr
Abstract—Porcine coronary arteries with regenerated endothelium exhibit impaired endothelium-dependent relaxations. Experiments were designed to analyze the structural and functional changes occurring in regenerated endothelial cells. Primary cultures from regenerated endothelium contained giant endothelial cells, with an increased number of cells with diameter >14.5 µm, a reduced ability to proliferate, and signs of apoptosis. The uptake of fluorescent acetylated LDL was increased 2-fold in cultures from regenerated endothelium. The increased uptake of acetylated LDL was confirmed ex vivo in injured coronary arteries. In cultures from regenerated endothelium, cGMP production was decreased under basal conditions and during stimulation with serotonin, bradykinin, and A23187. Thus, during regeneration, there is accelerated senescence of endothelial cells accompanied by increased incorporation of modified LDL and reduction of NO production without decrease in endothelial NO synthase expression. These alterations help to explain the altered endothelium-dependent responses 28 days after balloon injury.
Key Words: endothelial dysfunction • modified LDL • cGMP • endothelial NO synthase • senescence
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