lood vessels distribute entire body, supplying oxygen and nutrient. Endothelial cells (ECs) cover the entire inner lumen of the
vessels and form interface between blood and vasculature; therefore receive continuous mechanical and/or chemical stresses.
Accumulation of damages to ECs is thought to be the primary cause of various vascular diseases including atherosclerosis, diabetic
vascular complication and so forth. We recently isolated vasohibin-1 (VASH1) as a novel angiogenesis inhibitor produced by ECs,
and its homologue vasohibin-2 (VASH2). Human VASH1 gene is encoded in 14q24.3 while human VASH2 gene is encoded in
1q32.3, and these 2 molecules are highly conserved between species.
Angiogenesis is controlled by the local balance between its stimulators and inhibitors. In general, angiogenesis stimulators
promote EC survival, whereas angiogenesis inhibitors induce EC death and vascular regression. Since VASH1 is synthesized by
ECs and inhibits angiogenesis, VASH1 can be a suicidal molecule. We therefore characterized the role of VASH1 in EC survival/
death. To our surprise, overexpression of VASH1 in ECs increased stress resistance and prevented cell death induced by cellular
stresses including H2O2 or serum starvation, whereas the knockdown of VASH1 induced premature senescence of ECs, and
those ECs were easily killed by cellular stresses. These results indicate that VASH1 plays important role not only in angiogenesis
inhibition but also in vascular maintenance. The molecular mechanism of VASH1-mediated stress resistance and possible relation
to glomerular function will be discussed in the meeting.
Dr. Sato is a full Professor of the Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University. He received his M.D. from Kobe University in 1978 and his Ph.D. from Kyushu University in 1987. He was a postdoctoral fellow at New York University Medical Center from 1987 to 1989. He returned to Oita Medical University as an assistant Professor in 1989, and promoted to the present position in 1994. He published more than 150 peer-reviewed original papers, and is now appointed as the president of the Japanese Vascular Biology and Medicine Organization
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