Abstract
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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Takata K, Matsuzaki T, Tajika Y (2004) Aquaporins: water channel proteins of the cell membrane. Prog Histochem Cytochem 39:1–83
Hasegawa H, Lian SC, Finkbeiner WE, Verkman AS (1994) Extrarenal tissue distribution of CHIP28 water channels by in situ hybridization and antibody staining. Am. J. Physiol 266: C893–C903
Nielsen S, King LS, Christensen BM, Agre P (1997) Aquaporins in complex tissues. II. Subcelluar distribution in respiratory and glandular tissues of rat. Am J Physiol 273:C1549–C1561
Nielsen S, Smith BL, Christensen EI, Agre P (1993) Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia. Proc Natl Acad Sci USA 90:7275–7279
Jonker S, Davis LE, van der Bilt JD, Hadder B, Hohimer AR, Giraud GD, Thornburg KL (2003) Anaemia stimulates aquaporin 1 expression in the fetal sheep heart. Exp Physiol 88:691–698
Suleymanian MA, Baumgarten CM (1996) Osmotic gradientinduced water permeation across the sarcolemma of rabbit ventricular myocytes. J Gen Physiol 107:503–514
Page E, Winterfield J, Goings G, Bastawrous A, Upshaw-Earley J (1998) Water channel proteins in rat cardiac myocyte caveolae: osmolarity-dependent reversible internalization. Am J Physiol 274: H1988–H2000
Butkus A, Alcorn D, Earnest L, Moritz K, Giles M, Wintour EM (1997) Expression of aquaporin-1 (AQP1) in the adult and developing sheep kidney. Biol Cell 89:313–320
Jonker S, Davis LE, van der Bilt JD, Hadder B, Hohimer AR, Giraud GD, Thornburg KL (2003) Anaemia stimulates aquaporin 1 expression in the fetal sheep heart. Exp Physiol 88:691–698
Saadoun S, Papadopoulos MC, Hara-Chikuma M, Verkman AS (2005) Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature 434:786–792
Ma B, Xiang Y, Mu SM, Li T, Yu HM, Li XJ (2004) Effects of acetazolamide and anordiol on osmotic water permeability in AQP1-cRNA injected Xenopus oocyte. Acta Pharmacol Sin 25:90–97
Xiang Y, Ma B, Li T, Gao JW, Yu HM, Li XJ (2004) Acetazolamide inhibits aquaporin-1 protein expression and angiogenesis. Acta Pharmacol Sin 25:812–816
Park JW, Roh HY, Jung IS, Yun YP, Yi KY, Yoo SE, Kwon SH, Chung HJ, Shin HS (2005) Effects of [5-(2-methoxy-5-fluorophenyl) furan-2-ylcarbonyl] guanidine (KR-32560), a novel sodium/hydrogen exchanger-1 inhibitor, on myocardial infarct size and ventricular arrhythmias in a rat model of ischemia/reperfusion heart injury. J Pharmacol Sci 98:439–449
Zheng W, Weiss RM, Wang X, Zhou R, Arlen AM, Lei L, Lazartigues E, Tomanek RJ (2004) DITPA stimulates arteriolar growth and modifies myocardial postinfarction remodeling. Am J Physiol Heart Circ Physiol 286:H1994–H2000
Lanza R, Moore MA, Wakayama T, Perry AC, Shieh JH, Hendrikx J, Leri A, Chimenti S, Monsen A, Nurzynska D, West MD, Kajstura J, Anversa P (2004) Regeneration of the infarcted heart with stem cells derived by nuclear transplantation. Circ Res 94:820–827
Rosolowsky M, Weiss HR (1986) Quantitative morphometric determination of arteriolar and capillary perfusion within ischemic rabbit left ventricle. Microvasc Res 32:99–111
Couffinhal T, Silver M, Zheng LP, Kearney M, Witzenbichler B, Isner JM (1998) A mouse model of angiogenesis. Am J Pathol 152:1667–1679
Weis S, Shintani S, Weber A, Kirchmair R, Wood M, Cravens A, McSharry H, Iwakura A, Yoon Y, Himes N, Burstein D, Doukas J, Soll R, Losordo D, Cheresh D (2004) Src blockade stabilizes a Flk/cadherin complex, reducing edema and tissue injury following myocardial infarction. J. Clin. Invest 113:885–894
Ma B, Xiang Y, Li T, Yu HM, Li XJ (2004) Inhibitory effect of topiramate on Lewis lung carcinoma metastasis and its relation with AQP1 water channel. Acta Pharmacol Sin 25(1):54–60
Heba G, Krzeminski T, Porc M, Grzyb J, Ratajska A, Dembinska-Kiec A (2001) The time course of tumor necrosis factor-α, inducible nitric oxide synthase and vascular endothelial growth factor expression in an experimental model of chronic myocardial infarction in rats. J Vasc Res 38:288–300
Fukuda S, Kaga S, Sasaki H, Zhan L, Zhu L, Otani H, Kalfin R, Das DK, Maulik N (2004) Angiogenic signal triggered by ischemic stress induces myocardial repair in rat during chronic infarction. J Mol Cell Cardiol 36:547–559
Kawata H, Yoshida K, Kawamoto A, Kurioka H, Takase E, Sasaki Y, Hatanaka K, Kobayashi M, Ueyama T, Hashimoto T, Dohi K (2001) Ischemic preconditioning upregulates vascular endothelial growth factor mRNA expression and neovascularization via nuclear translocation of protein kinase C epsilon in the rat ischemic myocardium. Circ Res 13:696–704
Camerino GM, Nicchia GP, Dinardo MM, Ribatti D, Svelto M, Frigeri A (2006) In vivo silencing of aquaporin-1 by RNA interference inhibits angiogenesis in the chick embryo chorioallantoic membrane assay. Cell Mol Biol (Noisy-le-grand) 52(7):51–56
Kaneko K, Yagui K, Tanaka A, Yoshihara K, Ishikawa K, Takahashi K, Bujo H, Sakurai K, Saito Y (2008) Aquaporin 1 is required for hypoxia-inducible angiogenesis in human retinal vascular endothelial cells. Microvasc Res 75(3):297–301
Ogura T, Imanishi S, Shibamoto T (2002) Osmometric and watertransporting properties of guinea pig cardiac myocytes. Jpn J Physiol 52(4):333–342
Ruiz-Ederra J, Verkman AS (2006) Accelerated cataract formation and reduced lens epithelial water permeability in aquaporin-1-deficient mice. Invest Ophthalmol Vis Sci 47(9):3960–3967
Hub JS, de Groot BL (2006) Does CO2 permeate through Aquaporin-1? Biophys J 91(3):842–848
Xiang Y, Ma B, Li T, Yu HM, Li XJ (2002) Acetazolamide suppresses tumor metastasis and related protein expression in mice bearing Lewis lung carcinoma. Acta Pharmacol Sin 23:745–751
Banai S, Chandra M, Lazarovici G, Keshet E, Pinson A, Shweiki D (1994) Upregulation of vascular endothelial growth factor expression induced by myocardial ischemia: implication for coronary angiogenesis. Cardiovasc Res 28:1176–1179
Matsunaga T, Warltier DC, Weihrauch DW, Moniz M, Tessmer J, Chilian WM (2000) Ischemia-induced coronary collateral growth is dependent on vascular endothelial growth factor and nitric oxide. Circulation 102:3098–3103
Biselli PM, Guerzoni AR, de Godoy MF, Pavarino-Bertelli EC, Goloni-Bertollo EM (2008) Vascular endothelial growth factor genetic variability and coronary artery disease in Brazilian population. Heart Vessels 23(6):371–375
Doi K, Ikeda T, Marui A, Kushibiki T, Arai Y, Hirose K, Soga Y, Iwakura A, Ueyama K, Yamahara K, Itoh H, Nishimura K, Tabata Y, Komeda M (2007) Enhanced angiogenesis by gelatin hydrogels incorporating basic fibroblast growth factor in rabbit model of hind limb ischemia. Heart Vessels 22(2):104–108
Ruiz-Ederra J, Verkman AS (2007) Aquaporin-1 independent microvessel proliferation in a neonatal mouse model of oxygeninduced retinopathy. Invest Ophthalmol Vis Sci 48(10):4802–4810
Author information
Authors and Affiliations
Corresponding author
Additional information
These authors contributed equally to this work.
Rights and permissions
About this article
Cite this article
Ran, X., Wang, H., Chen, Y. et al. Aquaporin-1 expression and angiogenesis in rabbit chronic myocardial ischemia is decreased by acetazolamide. Heart Vessels 25, 237–247 (2010). https://doi.org/10.1007/s00380-009-1179-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00380-009-1179-5