Smoking, cadmium accumulation and aortic aneurysm

Background: Smoking is an important risk factor for abdominal aortic aneurysm (AAA), a disorder associated with loss of medial smooth muscle cells. Cadmium, one of the toxic components inhaled in cigarette smoke, is known to alter the metabolism of aortic smooth muscle cells. This was an investigation of the hypothesis that excess cadmium accumulation in the abdominal aorta is associated with the development of aneurysms. Methods: Samples of abdominal aorta were obtained at the time of surgery from 12 patients with AAA (seven men and five women, mean age 72 years) and at autopsy from 17 patients (ten men and seven women, mean age 76 years) with an undilated aorta (diameter 1·6–2·2 cm). The smoking history of all patients was noted. The aorta was dissected into three layers, intima, media and adventitia; each was dried to a constant weight, hydrolysed and cadmium was measured by atomic absorption spectrometry. In separate experiments 5‐bromo‐2′‐deoxyuridine uptake and picogreen assay of DNA were used to investigate the effect of cadmium on the proliferation of cultured aortic smooth muscle cells. Results: The mean(s.e.) cadmium content of the intima, media and adventitia was 1·14(0·24), 3·25(0·53) and 1·87(0·38) ng per mg dry weight respectively; the medial concentration was significantly higher than the concentration in the other two layers ( P < 0·005). The medial cadmium content was similar in AAA and normal diameter aortas: 3·65(1·00) and 2·97(0·59) ng per mg dry weight respectively. Only trace amounts of cadmium were present in the aorta of those who had never smoked and there was a strong positive association between medial cadmium content and pack‐year history of smoking ( r s = 0·87, P < 0·001). Cadmium inhibited the proliferation of smooth muscle cells cultured on polymeric collagen, 5‐bromo‐2′‐deoxyuridine uptake (IC 50 1·4 nmol l −1 ) and DNA content (IC 50 6·3 nmol l −1 ). Cadmium was less toxic, by more than tenfold, to smooth muscle cells cultured on fibronectin, monomeric collagen or plastic. Conclusion: Cadmium accumulates selectively in the medial layer of the abdominal aorta of smokers, where it may inhibit DNA synthesis and proliferation of smooth muscle cells. The toxic effects of cadmium on cultured smooth muscle cells depend on their underlying matrix and this may explain why the accumulation of cadmium in aortic media was not associated with the development of aneurysms. © 2000 British Journal of Surgery Society Ltd