Differential expression of protease-activated receptors 1, 2, and 4 on human endothelial cells from different vascular sites.
OBJECTIVE
Protease-activated receptors (PARs) mediate DNA synthesis in endothelial cells when activated by serine proteases. However, despite the existence of heterogeneity among endothelial cells from each tissue, the responses to PAR-1, PAR-2, and PAR-4 activation are poorly defined and compared between endothelial cells from different sites. The aim of this study was to investigate whether PAR-mediated DNA synthesis differed in various endothelial cell types.


METHODS
We examined the incorporation of BrdU by human pulmonary artery endothelial cells (HPAECs), human aortic endothelial cells (HAECs), and human umbilical vein endothelial cells (HUVECs).


RESULTS
When the endothelial cells were treated with the selective PAR-1-activating peptide, SFLLRN, HAECs showed the highest BrdU incorporation rate (182 +/- 28%). In contrast, treatment with the PAR-2-activating peptide, SLIGKV, resulted in the highest BrdU incorporation rate (173 +/- 37%) in HPAECs, when pretreated with TNF-alpha. The PAR-4-activating peptide, GYPGQV, induced DNA synthesis in HPAECs and HAECs, but not in HUVECs.


CONCLUSIONS
These findings suggest that each PAR preferentially targets an endothelial cell type, and thus plays a distinct role in diverse physiological or pathological conditions.
Fujiwara
Masakazu
M
Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
Jin
Enjing
E
Ghazizadeh
Mohammad
M
Kawanami
Oichi
O
D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D044463:Receptor, PAR-1 / Q000096:biosynthesis* / Q000187:drug effects; D044464:Receptor, PAR-2 / Q000096:biosynthesis* / Q000187:drug effects; D018179:Receptors, Thrombin / Q000096:biosynthesis* / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013917:Thrombin / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D009842:Oligopeptides; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C109968:seryl-leucyl-isoleucyl--glycyl-lysyl-valine; D013917:Thrombin; C112908:protease-activated receptor 4