Gene expression in endothelial cells and intimal smooth muscle cells in atherosclerosis-prone or atherosclerosis-resistant regions of the human aorta

• Published in: Journal of vascular research Vol. 45; no. 4; p. 303
• Main Authors: Wara, A K M Khyrul, Mitsumata, Masako, Yamane, Tetsu, Kusumi, Yoshiaki, Yoshida, Yoji
• Format: Journal Article
• Language: English
• Published: Switzerland 01-01-2008
• Subjects: Adult; Aged; Aorta - cytology; Aorta - metabolism; Atherosclerosis - etiology; Elastin - physiology; Endothelial Cells - metabolism; Endothelium, Vascular; Female; Gene Expression Profiling; Humans; Male; Middle Aged; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle - metabolism; RNA, Messenger - analysis; Stress, Mechanical
• ISSN: 1423-0135
• DOI: 10.1159/000113602

We compared the atherogenic gene expression in the intimas of atherosclerosis-prone regions (proximal walls), which are exposed to disturbed shear stress, and atherosclerosis-resistant regions (apices), which are exposed to unidirectional laminar shear stress, at the orifices of the intercostal arteries of human aortas.
Expression of mRNAs, detected by in situ RT-PCR, for IL-1 beta, TNF-alpha, VCAM-1, PAF receptor and GRP in endothelial cells (ECs), and of PDGF receptor beta (PDGFR-beta), MCP-1, GRP and collagen type-1 by smooth muscle cells (SMCs) in the proximal walls, was significantly enhanced, while seldom observed in the elastic-hyperplastic layer of the apices. Protein expression of PDGFR-beta, IL-1 beta and TNF-alpha was also observed on the proximal walls. SMC growth in the apices was inhibited. Cultured SMC growth and their expression of PDGFR-beta were also significantly inhibited by elastin.
These results suggest that the construction of the elastic-hyperplastic layer and the subsequent inhibition of SMC growth by elastin, with stabilized ECs under unidirectional laminar shear stress, resulted in atherosclerosis-resistant regions at the apices of human aortas, and that the continuous induction of atherogenic gene expression by ECs activated by disturbed shear stress inhibits the formation of atherosclerosis-resistant intima along the proximal walls.