Long-term nicotine exposure increases aortic endothelial cell death and enhances transendothelial macromolecular transport in rats.

Abstract

Repeated endothelial cell injury has been suggested as an initiating factor in atherogenesis. Dying or dead endothelial cells have been shown to make significant contributions to the local enhancement of transendothelial macromolecular transport. Since cigarette smoking is one of the major risk factors for atherosclerosis, we examined the hypothesis that smoking accelerates atherogenesis by increasing the frequency of endothelial cell death and hence transendothelial macromolecular transport. Sixteen male Sprague-Dawley rats were given nicotine at a weight-adjusted dose of 5 mg/kg body wt per day in their drinking water over a period of 6 weeks. A group of 16 age-matched male Sprague-Dawley rats not exposed to nicotine and maintained over the same time period served as the control group. In en face preparations of thoracic aorta, immunoglobulin G-containing dying or dead endothelial cells were identified by the indirect immunoperoxidase method, and endothelial leakage to Evans blue-albumin (EBA) complexes (5 minutes after intravenous injection) was visualized by fluorescence microscopy. The results showed that in nicotine-treated rats, 51% of dead endothelial cells were associated with EBA leakage, which was responsible for 57% of total EBA leaky foci. C igarette smoking is generally accepted to be one of the major risk factors for coronary heart disease. 1 -6 The potential for developing coronary heart disease in male cigarette smokers is approximately two times greater than in male nonsmokers. 7Large epidemiological surveys have shown that the incidence of morbidity and mortality from coronary heart disease increases progressively with the number of cigarettes smoked. 68 Smoking cessation has been demonstrated to be associated with a decline in cardiovascular death.9 Autopsy studies have also revealed the increased occurrence of advanced atherosclerotic le-

Macro-microangiopathy and endothelial dysfunction in NIDDM patients with and without diabetic nephropathy

“…The association between smoking and elevated TER alb in our NIDDM patients has also been demonstrated in non-diabetic subjects [52]. Several factors may contribute such as carbon monoxide [53], nicotine [54], and acute intermittent blood pressure elevation in association with smoking [55].…”

“…Furthermore, repeated endothelial cell injury and increased lipid entry have been suggested as initiating events in atherogenesis [60]. Animal studies have demonstrated increased aortic endothelial cell death and enhanced transendothelial macromolecular transport in experimental diabetes, hypertension, and during nicotine consumption [54,61,62]. Diabetes, hypertension, cigarette smoking are well-known risk factors for macroangiopathy.…”

Nornicotine impairs endothelial cell-cell adherens junction complexes in EA.hy926 cell line via structural reorganization of F-actin

“…Yet In our unpublished studies, 24 h treatment of EA.hy926 cells with 25% and 50% CSE prepared from burning three cigarettes per 10 ml culture medium induced mostly early apoptosis (unpublished data). An in vivo increase in cell death frequency was observed by Lin et al following treatment of rats with nicotine [33].…”

Effects of cigarette smoking on early medial collateral ligament healing in a mouse model

“…[33][34][35] In this study, the lack of evidence for apoptosis in either the smoking animals or the nonsmoking controls demonstrated that programmed cell death is not a normal part of the early healing response in the mouse MCL and that increased apoptosis was not responsible for the decreased cell density in the injured ligament of mice exposed to cigarette smoke.…”