Overexpression of heme oxygenase-1 in coronary atherosclerosis of Japanese autopsies with diabetes mellitus: Hisayama study.
Few studies regarding the topographical expression of heme oxygenase-1 (HO-1) and its pathophysiological role in human coronary atherosclerotic lesions, particularly in relation to type 2 diabetes mellitus (DM) and intimal angiogenesis, have been reported. HO-1 expression was immunohistochemically examined in 312 tissue blocks of coronary arteries obtained from 53 Japanese autopsy cases in Hisayama cohort study that included 19 diabetic subjects and 34 age- and sex-matched non-diabetic subjects (56-93 years old, mean+/-S.D.: 73+/-10). The HO-1 was ubiquitously distributed in atherosclerotic intima, and was mainly expressed by macrophages and endothelial cells, and partly by smooth muscle cells. The prevalence of HO-1 expression increased as the lesion type (as classified by the American Heart Association (AHA) Committee) and stenotic grade progressed (p<0.0001), and was significantly higher in diabetic than in non-diabetic subjects (p<0.01). This HO-1 overexpression was associated with greater CD-68-positive macrophage infiltration (p=0.005). Interestingly, the distribution of HO-1-positive cells was accentuated in coronary atherosclerotic lesions with intimal microvessels in diabetic subjects (p<0.05), particularly those with hypercholesterolemia (p<0.05), and was preferentially distributed in the shoulder region of atherosclerotic lesion type IV in the AHA classification (p<0.01). In conclusion, HO-1 expression was distributed in overall human coronary atherosclerotic lesions, particularly in diabetic subjects, indicating that HO-1 expression is intimately associated with atherogenesis and may play an important role as an adaptive molecule in the inflammatory-repair process. The association of HO-1 overexpression with a greater extent of intraplaque angiogenesis suggests a multi-faceted role for HO-1 in modulating the progression of atherosclerosis.
Song
Jingyu
J
Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Sumiyoshi
Shinji
S
Nakashima
Yutaka
Y
Doi
Yasufumi
Y
Iida
Mitsuo
M
Kiyohara
Yutaka
Y
Sueishi
Katsuo
K
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D001344:Autopsy; D003324:Coronary Artery Disease / Q000208:ethnology* / Q000378:metabolism* / Q000473:pathology; D003331:Coronary Vessels / Q000201:enzymology / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000378:metabolism* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000208:ethnology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D018919:Neovascularization, Physiologic; D012307:Risk Factors
D051547:Heme Oxygenase-1