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.
Wang
D L
DL
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, R.O.C.
Tang
C C
CC
Wung
B S
BS
Chen
H H
HH
Hung
M S
MS
Wang
J J
JJ
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