Atherosclerosis and Lipoproteins |
From the Department of Vascular Surgery, Imperial College at Charing Cross, London, UK.
Correspondence to Prof J.T. Powell, University Hospitals of Coventry and Warwickshire, Clifford Bridge Road, Walsgrave, Coventry CV2 2DX, UK. E-mail Janet.Powell@wh-tr.wmids.nhs.uk or j.powell{at}ic.ac.uk
AbstractAbdominal aortic aneurysm is a smoking-related disorder. Cadmium, inhaled from cigarettes, may accumulate in the aorta and facilitate weakening of the aorta through adverse effects on smooth muscle cell metabolism. Cadmium was measured by atomic absorption spectrometry in infrarenal aortas from 13 patients with abdominal aortic aneurysm and from 17 age- and sex-matched patients with normal-diameter abdominal aorta. Total cadmium content was associated with smoking, assessed as pack-years (r=0.54, P=0.004), but was similar in aneurysmal and undilated aortas. The cadmium content (mean±SE) was higher in the media (3.25±0.53 ng/mg dry wt, 7±1.2 µmol/L) than in the intima or adventitia (1.14±0.24 and 1.87±0.38 ng/mg dry wt, respectively; ANOVA, P<0.005). There was a strong correlation between medial cadmium content and pack-years of smoking (r=0.87, P<0.001). In aortic smooth muscle cells cultured on fibrillar collagen, cadmium inhibited DNA synthesis and collagen synthesis and diminished cell numbers (IC50 2 µmol/L, 6 µmol/L, and 6 µmol/L, respectively), but higher concentrations of cadmium were required for upregulation of metallothionein (EC50 23 µmol/L). The cadmium content of the aorta increases in direct proportion to the pack-years of cigarettes smoked, with selective accumulation in the medial layer. However, the cadmium content of aneurysmal aortas was not higher than that of nondilated aortas for patients with matched smoking history. In smokers, the level of cadmium accumulation is probably sufficient to impair the viability of cultured smooth muscle cells. Similar mechanisms could underlie the development of degenerative aortic disease in smokers.
Key Words: aortas aneurysm smoking muscle smooth collagen
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