Cyclical strain increases endothelin-1 secretion and gene expression in human endothelial cells.
We examined the effects of cyclical strain on endothelin-1 (Et-1) secretion and Et-1 mRNA levels in human umbilical vein endothelial cells. Cultured endothelial cells grown on a flexible membrane base were deformed by vacuum to 20% of maximum strain, at 60 cycles/min, for various time periods. The rate of Et-1 release from strain- treated cells and their Et-1 mRNA levels were measured. Cells subjected to strain increased their Et-1 secretion into the culture medium from 0.17 ng/hr/10(6) cells to 0.44 ng/hr/10(6) cells. Concomitantly, the Et-1 mRNA levels in strained cells increased 1.4-, 2.1- or 2.6- fold (vs control unstrained cells) after 0.25, 0.5 or 6 hours of strain, respectively. Cells exposed to longer periods of strain (> 6 hrs) did not further increase their mRNA expression. Pretreatment with calphostin C, a specific inhibitor of protein kinase C, before straining completely abolished Et-1 mRNA expression. These results indicate that mechanical strain can modulate the secretion of Et-1 from endothelial cells by increasing Et-1 mRNA levels via the protein kinase C pathway. Elevation of Et-1 secretion and gene expression in endothelial cells under physiological strain might influence normal or pathological states of the vasculature and cardiac growth.
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, R.O.C.
D L
DL
Wang
C C
CC
Tang
B S
BS
Wung
H H
HH
Chen
M S
MS
Hung
J J
JJ
Wang
D002478:Cells, Cultured; D016232:Endothelins / Q000096:biosynthesis / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D013314:Stress, Mechanical; D013997:Time Factors; D014471:Umbilical Veins
D016232:Endothelins; D012333:RNA, Messenger; D011493:Protein Kinase C