Early Growth Response Factor-1 Is Associated With Intraluminal Thrombus Formation in Human Abdominal Aortic Aneurysm

• Published in: Journal of the American College of Cardiology 2009-03, Vol.53 (9), p.792-799
• Main Authors: Shin, In-Soon, MS, Kim, Jeong-Min, BS, Kim, Koung Li, MS, Jang, Shin Yi, PhD, Jeon, Eun-Seok, MD, PhD, Choi, Seung Hyuk, MD, PhD, Kim, Duk-Kyung, MD, PhD, Suh, Wonhee, PhD, Kim, Young-Wook, MD, FACS
• Format: Article
• Language: English
• Subjects: Abdomen; abdominal aortic aneurysm; Aged; Animals; Aortic Aneurysm, Abdominal - physiopathology; Aortic Aneurysm, Abdominal - surgery; Biological and medical sciences; Blood and lymphatic vessels; Blood clots; Blood platelets; Cardiology; Cardiology. Vascular system; Cardiovascular; Cell culture; Dehydrogenases; Deoxyribonucleic acid; Diseases of the aorta; DNA; Early Growth Response Protein 1 - biosynthesis; early growth response-1; Endothelium, Vascular - physiopathology; Female; Humans; Inflammation - physiopathology; Internal Medicine; Male; Medical sciences; Mice; Models, Biological; Muscle, Smooth, Vascular - physiopathology; Muscular system; Pathogenesis; Polymerase chain reaction; Shear stress; Smooth muscle; Studies; Thromboembolism - physiopathology; thrombus; Time Factors; tissue factor; Up-Regulation
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2008.10.055

Objectives The goal of this study was to investigate the expression of early growth response-1 (Egr-1), a vascular pathogenic transcription factor, and its potential relationship with tissue factor (TF), a key player during the thrombus formation in the abdominal aortic aneurysm (AAA) wall. Background Although intraluminal thrombus is a common finding in human AAA, the molecular mechanism of the thrombus formation has not been studied. Methods During the elective AAA repair, specimens were taken from the thrombus-covered and thrombus-free portions of the aneurysmal wall in each of 16 patients with AAA and analyzed to assess the differential expression of Egr-1 and TF. The proinflammatory and prothrombogenic activities of Egr-1 in vasculature were evaluated in vitro and in vivo by overexpressing it using adenovirus. Results The expression of both Egr-1 and TF was significantly increased in the thrombus-covered wall compared with the thrombus-free wall, in which their up-regulation in the thrombus-covered wall was strongly correlated with each other (p < 0.005, r = 0.717). Adenoviral overexpression of Egr-1 in human vascular smooth muscle and endothelial cells was found to up-regulate the expression of TF and inflammation-related genes. Moreover, Egr-1 overexpression in endothelial cells increased their adhesiveness to monocytes and also substantially promoted the intravascular thrombus formation in vivo, as shown in the inferior vena cava ligation experiment of the rat. Conclusions The present study demonstrates the differential up-regulation of Egr-1 in the thrombus-covered wall of human AAA and also suggests its possible contribution to the thrombogenic and inflammatory pathogenesis in human AAA.