Angiotensin-Converting Enzyme Effects of Smoking and Other Risk Factors for Cardiovascular Diseases

University dissertation from Linköping : Linköping University Electronic Press

Abstract: Cardiovascular diseases (CVDs) are the most common cause of death in Western countries. Smoking, hypertension, diabetes mellitus and hypercholesterolemia are considered as major risk factors. However, the underlying mechanisms by which these factors cause CVDs are not entirely clear. Angiotensin-converting enzyme (ACE) is a key enzyme in the renin-angiotensin-aldosterone system, converting angiotensin I to the vasoactive peptide angiotensin II. Besides being an important factor for normal regulation of blood pressure, ACE appears to be involved in the pathogenesis of atherosclerosis. Previous studies have shown an upregulation of ACE in atherosclerotic plaques. There is genetic polymorphism in the ACE gene (ACE I/D polymorphism) which is strongly connected to the levels of ACE in plasma, but has also been associated with higher risk for cardiovascular diseases. The aim of this thesis was to investigate ACE in vitro and in vivo, in relation to cardiovascular risk factors and CVDs. The results showed that nicotine and nicotine metabolites increase ACE activity in human endothelial cells in vitro. Smoking was associated with increased plasma ACE levels. This effect might be mediated by nicotine and nicotine metabolites. These results could explain one cellular mechanism by which smoking exerts negative effect on the vascular system. Extract of oral snuff inhibited ACE in human endothelial cells and in serum, whereas extract of cigarette smoke had no effect on endothelial ACE. If these results have any physiological relevance remains to be investigated. Cardiovascular risk factors and CVDs were associated with increased levels of ACE in plasma. No association between ACE D/D genotype and CVDs was found. Based on these results we suggest that an increased level of ACE, rather than ACE genotype, is associated with increased risk for CVDs.