Endothelial Cell Apoptosis is Responsible for the Formation of Coronary Thrombotic Atherosclerotic Plaques

Endothelial Cell Apoptosis is Responsible for the Formation of Coronary Thrombotic Atherosclerotic Plaques

FENG XU,^1,2 YANING SUN,³ YUGUO CHEN,^1,2 YI SUN,^1,2 RUIJIAN LI,^1,2 CHUNXI LIU,¹ CHENG ZHANG,^1,4 RONG WANG¹ and YUN ZHANG^1,4

¹Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Jinan, China
²Department of Emergency Medicine and Center of Chest Pain, Qilu Hospital of Shandong University, Jinan, China
³Department of Cardiology, Shandong Province Hospital affiliated to Shandong University, Jinan, China
⁴Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China

Ischemic manifestations of atherosclerosis are mainly due to thrombus formation upon superficially eroded (denudation of luminal endothelium) plaques or deeply ruptured (fibrous cap rupture) plaques. Eroded plaques, atherosclerotic plaques without rupture, are found common in young patients of sudden death with coronary thrombosis. Our study aimed to investigate the role of endothelial cell (EC) apoptosis in eroded plaque with thrombosis using an atherosclerotic rabbit model. Atherosclerotic plaques were established by post-balloon-injury high-cholesterol feeding in 33 rabbits. After three-month feeding, a 2-cm segment of plaque-rich abdominal aorta for each animal was clamped in vivo and filled with staurosporine, which induces endothelial apoptosis, or saline for 20 minutes. Three days later, serum lipids and high sensitive C-reactive protein (hs-CRP), a valuable inflammatory parameter, were quantified, and abdominal aorta angiography was conducted. In addition, immunohistochemistry staining was performed for all processed aortae. In the staurosporine-treated aorta, endothelium integrity of plaques was disrupted partially or in large areas, but fibrous cap rupture was not observed, the findings of which were similar to eroded plaques detected in human subjects. As compared to saline controls, staurosporine-treated rabbits showed higher apoptosis scores and thrombotic scores, and more angiographic overt thrombosis and histological thrombosis (P < 0.01, respectively), despite the similar serum levels of lipids and hs-CRP. We further confirmed that apoptosis score was linearly associated with thrombotic score. These results suggest that endothelial apoptosis may be an independent risk factor for thrombosis. In conclusion, the increase in endothelial apoptosis is involved in the formation of thrombotic eroded plaques.

Keywords —— Atherosclerosis; Eroded plaque; Endothelial cell; Apoptosis; Sudden coronary death.

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Tohoku J. Exp. Med., 2009, 218, 25-33

Correspondence: Yuguo Chen, M.D., Ph.D., 107 Wenhua Xi Road, Department of Emergency Medicine and Center of Chest Pain, Qilu Hospital of Shandong University, Jinan, 250012, P.R. China.

e-mail: warmsunlight2006@yahoo.com.cn