Phenotypic and Functional Changes in Regenerated Porcine Coronary Endothelial Cells

Abstract

Porcine coronary arteries with regenerated endothelium exhibit impaired endothelium-dependent relax-ations. 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 m, 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. (Circ Res. 2000;86:854-861.)

Aging Enhances the Sensitivity of Endothelial Cells Toward Apoptotic Stimuli

“…Recent studies further demonstrate that senescent endothelial cells are detectable in reendothelialized areas of the vascular wall after repeated balloon injury. 41,42 In accordance with the data of the present study, these regenerated endothelial cells were characterized by a reduced NO synthesis. 41 Therefore, one may hypothesize that the reendothelialized regions are predisposed to apoptosis induction, which may accelerate endothelial cell aging and further reduce NO synthesis.…”

Novel Stable Camptothecin Derivatives Replacing the E-Ring Lactone by a Ketone Function Are Potent Inhibitors of Topoisomerase I and Promising Antitumor Drugs

“…A primary culture of porcine aortic endothelial cells (PAEC) was used to investigate the effect of the drugs on rapidly proliferating normal cells (doubling time of 17 h). The PAEC cells were collected and cultured as described previously (Fournet-Bourguignon et al, 2000). All of the cells were grown at 37°C in a humidified atmosphere containing 5% CO 2 in RPMI 1640 or Dulbecco's modified Eagle's medium media supplemented with 10% fetal calf serum, 2 mM glutamine, 100 IU/ml penicillin, and 100 g/ml streptomycin.…”

Upregulation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in endothelial cells by nitric oxide deficiency

“…Impaired endothelium-dependent vasorelaxation precedes the development of clinical manifestations of the disease and is detectable even before angiographic manifestations become apparent (2,9,14,20,36). One of the mechanisms leading to endothelial dysfunction is the accumulation of an endogenous inhibitor of eNOS, asymmetric dimethylarginine (ADMA) (1,8,13,31,43,46). Plasma levels of ADMA are elevated in patients with chronic renal failure (11,21,22,32,34,44,49), hypercholesterolemia (8, 9, 29, 47), occlusive vascular disease, and hypertension (1, 5, 14, 16 -18, 20, 42, 43, 48) and associated with reduced NO production and impaired endotheliumdependent vasodilation.…”