Cadmium Accumulation in Aortas of Smokers

Abstract

Abstract-Abdominal 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 (rϭ0.54, Pϭ0.004), but was similar in aneurysmal and undilated aortas. The cadmium content (meanϮSE) was higher in the media (3.25Ϯ0.53 ng/mg dry wt, 7Ϯ1.2 mol/L) than in the intima or adventitia (1.14Ϯ0.24 and 1.87Ϯ0.38 ng/mg dry wt, respectively; ANOVA, PϽ0.005). There was a strong correlation between medial cadmium content and pack-years of smoking (rϭ0.87, PϽ0.001). In aortic smooth muscle cells cultured on fibrillar collagen, cadmium inhibited DNA synthesis and collagen synthesis and diminished cell numbers (IC 50 2 mol/L, 6 mol/L, and 6 mol/L, respectively), but higher concentrations of cadmium were required for upregulation of metallothionein (EC 50 23 mol/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 Ⅲ aneurysm Ⅲ smoking Ⅲ muscle smooth Ⅲ collagen C admium is one of the many toxic components of inhaled tobacco smoke. The amount of cadmium inhaled from each pack of 20 cigarettes is Ϸ16 g. 1 Cadmium has a long elimination time (estimated at 10 to 30 years), providing the possibility for the accumulation of substantial amounts of cadmium during the lifetime of a smoker. There are reports that cadmium alters the metabolism of cultured human aortic smooth muscle cells and the processing of collagen. 2,3 Cadmium also blocks calcium channels and inhibits ATPases and other ion transport systems.Smoking is the most consistent risk factor for the development and expansion of abdominal aortic aneurysms (AAAs). 4,5 The histological features of AAA include atherosclerosis, loss of medial smooth muscle (with evidence of apoptosis), and loss of elastin (with remodeling of the connective tissue). Therefore, we wished to investigate the hypothesis that cadmium, from cigarettes, accumulates in the infrarenal abdominal aorta, thus stimulating aneurysmal dilatation. To test this hypothesis, we compared the concentration of cadmium in infrarenal aortas from patients with and without AAAs.After finding that the highest concentration of cadmium was in the medial layer of the aorta, we investigated whether similar concentrations of cadmium altered the metabol...

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