Phenotypic and functional changes in regenerated porcine coronary endothelial cells - Increased uptake of modified LDL and reduced production of NO

Porcine coronary arteries with regenerated endothelium exhibit impaired end othelium-dependent relaxations, Experiments were designed to analyze the st ructural 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 mu m, a reduce d ability to proliferate, and signs of apoptosis, The uptake of fluorescent acetylated LDL was increased 2-fold in cultures from regenerated endotheli um. The increased uptake of acetylated LDL was confirmed ex vivo in injured coronary arteries. In cultures from regenerated endothelium, cGMP producti on was decreased under basal conditions and during stimulation with seroton in, 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 endo thelium-dependent responses 28 days after balloon injury.