Angiotensin-converting enzyme expression in human carotid artery atherosclerosis

Angiotensin-converting enzyme (ACE) inhibitors reduce the progression of at herosclerosis in animal models and reinfarction rates after myocardial infa rction in humans. Although expression of components of the renin-angiotensi n system has been reported in human coronary arteries, no data regarding th eir presence in carotid arteries, a frequent site for the occurrence of ath erosclerosis plaques, are available. The following study sought to determin e whether ACE mRNA and protein can be detected in human carotid atheromatou s lesions. Twenty-four intact endarterectomy specimens were obtained from p atients with severe carotid occlusive disease (17 males and 7 females, aged 68+/-1 years) and fixed within 30 minutes. Carotid artery specimens contai ned advanced Stary type V and VI lesions, and human ACE mRNA expression and protein were localized in cross sections by the combination of in situ hyb ridization and immunohistochemistry. Cell type-specific antibodies were use d to colocalize ACE to smooth muscle cells, endothelial cells, macrophages, or lymphocytes. ACE protein was localized in the intima, whereas the overl ying media was largely free of ACE staining. In less complicated lesions, A CE staining was modest and could be visualized in scattered clusters of mac rophages and on the luminal side of carotid artery vascular endothelium. Sm ooth muscle cells were largely negative. ACE staining increased as lesions became more complex and was most prominent in macrophage-rich regions. The shoulder regions of plaques contained numerous ACE-positive macrophage foam cells and lymphocytes. In these areas, microvessels were positive for endo thelial cell and smooth muscle cell ACE expression. However, microvessels i n plaques free of inflammatory cells were stained only faintly for ACE expr ession. Labeling for ACE mRNA mirrored the pattern of protein expression, l ocalizing ACE mRNA to macrophages and microvessels within the intima. In co nclusion, atherosclerosis alters carotid artery ACE production, increasing transcription and translation within regions of plaque inflammation. These data provide another important mechanism by which inflammation associated w ith increased ACE expression may contribute to the progression of atheroscl erosis.