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


RESULTS
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.


CONCLUSIONS
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.
Wara
A K M Khyrul
AK
Cardiology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Mitsumata
Masako
M
Yamane
Tetsu
T
Kusumi
Yoshiaki
Y
Yoshida
Yoji
Y
D000328:Adult; D000368:Aged; D001011:Aorta / Q000166:cytology* / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology*; D004549:Elastin / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013314:Stress, Mechanical
D012333:RNA, Messenger; D004549:Elastin