Authors: Kazunori Otsui Nobutaka Inoue Seiichi Kobayashi Rio Shiraki Tomoyuki Honjo Motonori Takahashi Kenichi Hirata Seinosuke Kawashima Mitsuhiro Yokoyama
Publish Date: 2007/11/26
Volume: 22, Issue: 6, Pages: 416-422
Abstract
Tolllike receptors TLRs play an essential role in innate immunity as components of the primary defense system against microbial infections It has become evident that TLRs are also involved in the pathogenesis of various cardiovascular diseases However the expression patterns of TLRs in the human coronary arteries of coronary artery disease CAD patients and the regulatory mechanisms of their expression remain unknown The TLR4 expression patterns were invstigated by immunohistochemical analysis of coronary specimens obtained from autopsy cases or CAD patients by using directional coronary atherectomy In atherosclerotic coronary arteries n = 8 TLR4 immunoreactivity was colocalized with infiltrating inflammatory cells Interestingly vascular smooth muscle cells of atherosclerotic coronary arteries intensely expressed TLR4 even in the regions that had few inflammatory cells In contrast TLR4 expression was barely detected in the vascular smooth muscle cells of nonatherosclerotic coronary arteries n = 4 Furthermore intense expression of smooth muscle TLR4 was observed in the coronary arteries of CAD patients n = 52 Stimulation with tumor necrosis factor α and angiotensin II increased the expression of TLR4 mRNA in cultured human vascular smooth muscle cells Candesartan an antagonist of the angiotensin II type 1 receptor AT1 and Nacetylcystine inhibited angiotensin IIinduced TLR4 mRNA expression in these cells These findings suggest that the vascular smooth muscle cells of atherosclerotic coronary arteries may be activated to express TLR4 Furthermore proinflammatory cytokines and oxidative stress in the inflammatory lesions might contribute to the enhanced expression of TLR4 in vascular smooth muscle cells of atherosclerotic arteries
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