Aquaporin-1 expression and angiogenesis in rabbit chronic myocardial ischemia is decreased by acetazolamide.
Aquaporin-1 (AQP1) is a water channel protein expressed in endothelial and epithelial cells of many tissues, including the vasculature, where it serves to increase water permeability of the cell membrane. Prior studies have also reported that AQP1 plays a central role in tumor angiogenesis by promoting endothelial cell migration. To investigate whether AQP1 might also influence vascular angiogenesis in ischemic myocardium, the expression level of AQP1 for 21 days post myocardial infarction in rabbit hearts was observed. Aquaporin-1 mRNA and protein levels in day 3, and peaked on day 7 post surgery. This correlated well with the pattern of neovascularization and increased water content of infarct border tissue, and suggested that AQP1 may be involved in myocardial angiogenesis in response to ischemia injury. These AQP1-induced changes were tempered by acetazolamide, a carbonic anhydrase inhibitor, which acted by downregulating AQP1 expression. Acetazolamide treatment did not significantly affect the expression of vascular endothelial growth factor in the tissues studied. Our findings indicate a novel role for AQP1 in postnatal angiogenesis, which has implications in diverse pathophysiological conditions including wound healing, tumor metastasis, and organ regeneration.
Ran
Xun
X
Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, PR China.
Wang
Haoyu
H
Chen
Yucheng
Y
Zeng
Zhi
Z
Zhou
Qin
Q
Zheng
Rong
R
Sun
Jiayang
J
Wang
Bing
B
Lv
Xiaoyan
X
Liang
Yujia
Y
Zhang
Ke
K
Liu
Weiqiang
W
D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D051398:Aquaporin 1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D015536:Down-Regulation; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D002257:Carbonic Anhydrase Inhibitors; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D051398:Aquaporin 1; D000086:Acetazolamide