Biochemistry & Pharmacology: Open Access

Biochemistry & Pharmacology: Open Access
Open Access

ISSN: 2167-0501

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Editorial - (2014) Volume 3, Issue 1

On the Role of Aquaporins in Myocardial Injury

Marcelo Ozu*
Laboratorio de Biomembranas, Department of Physiology and Biophysics, School of Medicine, University of Buenos Aires, Argentina
*Corresponding Author: Marcelo Ozu, Laboratorio de Biomembranas, Department of Physiology and Biophysics, School of Medicine, University of Buenos Aires, Paraguay 2155, 7º Piso C1121ABG Ciudad Autónoma De Buenos Aires Buenos Aires, Argentina, Tel: +054-11-5950-9500 Exn. 2145 Email:

Abstract

The presence of aquaporins in the cardiovascular system has been well documented, however our knowledge
about their role in myocardial pathophysiology is now being elucidated. A brief overview of the presence, function and
regulation of aquaporins in myocardial injury is here presented.

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Editorial Text

Cardiopulmonary bypass (CPB) renders the myocardium susceptible to water imbalance and subsequent Myocardial edema (ME) as a consequence of decreased cardiac energy supply [1]. Factors leading to ME include hemodilution, ischemia and reperfusion, as well as osmotic gradients arising from pathological changes of the physiological state.

Several members of the aquaporin (AQP) family have been described in the myocardium [2]. The mRNA expression of AQP -1, -3, -5, -7, -9, -10, and -11 was detected in human hearts, while AQP -1, -4, -6, -7, -8, and -11 were detected in hearts from mice and rats [3]. The protein expression of AQP6 was detected inside the myocytes in mice, while AQP4 was exclusively observed on the intercalated discs between cardiac myocytes [4].

Experiments with AQP1 knock-out mice showed microcardia, decreased myocyte dimensions and low blood pressure [5]. On the other hand, knock-out mice for AQP7 showed a conserved cardiac morphology, although low content of glycerol and ATP was observed [6].

Nowadays, research is focused on the role that aquaporins play in myocardial injury. AQP -1, -4, and -6 seems to play different roles in myocardial infarction (MI) in mouse hearts. While the time dependent pattern of the observed up-regulated expression of AQP4 in MI coincides with that of ME and cardiac dysfunction, the expression of AQP1 and AQP6 persistently increase [4].

One of the first reports of aquaporins in heart revealed that AQP1 colocalizes with Caveolin-3 at 20°C and 37°C in rats [7]. Interestingly, when rat cardiac myocytes were exposed to hypertonic media AQP1 was reversibly internalized [7]. In addition, a more recent report showed that AQP1 cosegragates with Caveolin-1 in mice [5]. Recent works demonstrated that the levels of AQP1 mRNA and protein increase 12 hours after global myocardial ischemia in goats following CPB [8]. Moreover, the treatment with HgCl2 reduced ME, indicating that AQP1 is involved in the development of edema [8]. Other works showed that AQP1 expression is inversely correlated with the protein expression of Connexin 43 in goats following CPB [9]. Altogether, these evidences suggest an important role of AQP1 in the regulation of Connexin 43 in the progression of ME, and a related localization of AQP1 and Caveolin-1.

In mouse hearts AQP1 was shown to be localized at caveolae but also in endothelial cell membranes. Cardioplegia, ischemia and hypoxia decrease AQP1 mRNA as well as total protein expression and glycosylation [10]. In endothelium, AQP1 does not regulate the endothelium-derived hyperpolarizing factor (EDH (F)) or NOdependent relaxation, but its deletion increases prostanoids-dependent relaxation in resistance vessels [5]. AQP1 is involved in vascular angiogenesis in ischemic myocardium after myocardial infarction in rabbit hearts [11]. Acetazolamide (a carbonic anhydrase inhibitor) tempered the effects induced by AQP1 down regulating its expression [11].

The aquaporins expression in heart is regulated by changes of osmolarity. In this sense, it was demonstrated that hyperosmotic NaCl injections induce an up-regulation of AQP1 mRNA and the glycosylated fraction of the AQP1 protein in mice [12]. In the case of AQP4, it was demonstrated that both the mRNA and protein expression decreased in the mouse heart after hyperosmotic NaCl injections [12]. In rats AQP1 can be differentially regulated in response to hydration status [13]. By other side, experiments with AQP4 KO mice demonstrated that the cardiac weight index was increased after the treatment with Isoproterenol (a b-receptor agonist) and that the expression levels of FKBP12.6 (the cardiomyocyte subtype of the FK506 binding protein, which is essential for tight closing of the RyR2 channels during diastole), SERCA2a (sarcoplasmic reticulum Ca2+-ATPase2a), and CASQ2 (calsequestrin 2) were downregulated. In addition, the diastolic calcium concentrations increased [14]. According to the authors, these results indicate that AQP4 KO causes abnormalities of calcium modulating proteins leading to an exacerbation of risk for cardiac arrhythmias and failure. These changes are likely due to an increase in pro-inflammatory factors (ETA, pPKCε, NADPH oxidase p67phox) which are exacerbated by stress [14]. Other works demonstrated that AQP4 KO mice undergoing global ischemia and reperfusion had reduced infarct size and attenuated left ventricular end-diastolic pressure during reperfusion after cardiac ischemic injury [15]. Also AQP4 KO cardio-myocytes were partially resisted to hypoosmotic stress in the presence of hypercontracture of the left coronary artery [15]. Other evidences indicate that Diazoxide (a mitochondrial KATPchannel opener) may have impact on myocardial water balance and glycerol uptake by decreasing the relative expression of AQP7 during coronary artery bypass grafting in patients with stable coronary artery disease [16].

The role that aquaporins play in myocardial injury is being studied at present. Recent research evidences the importance of AQPs in the development of edema following cardiopulmonary bypass. Changes of water balance and alterations of the calcium homeostasis are associated with the myocardial aquaporins function. Further research of AQP regulation will contribute important knowledge about myocardial injury and possible treatment.

References

  1. Toraman F, Evrenkaya S, Yuce M, Turek O, Aksoy N, et al. (2004) Highly positive intraoperative fluid balance during cardiac surgery is associated with adverse outcome. Perfusion 19: 85-91.
  2. Egan JR, Butler TL, Au CG, Tan YM, North KN, et al. (2006) Myocardial water handling and the role of aquaporins. Biochim Biophys Acta 1758: 1043-1052.
  3. Butler TL, Au CG, Yang B, Egan JR, Tan YM, et al. (2006) Cardiac aquaporin expression in humans, rats, and mice. Am J Physiol Heart Circ Physiol 291: H705-713.
  4. Zhang HZ, Kim MH, Lim JH, Bae HR (2013) Time-dependent expression patterns of cardiac aquaporins following myocardial infarction. J Korean Med Sci 28: 402-408.
  5. Montiel V, Gomez EL, Bouzin C, Esfahani H, Romero Perez M, et al. (2014) Genetic deletion of aquaporin-1 results in microcardia and low blood pressure in mouse with intact nitric oxide-dependent relaxation, but enhanced prostanoids-dependent relaxation. Pflugers Arch. Eur J Physiol 466: 237-251.
  6. Hibuse T, Maeda N, Nakatsuji H, Tochino Y, Fujita K, et al. (2009) The heart requires glycerol as an energy substrate through aquaporin 7, a glycerol facilitator. Cardiovasc Res 83: 34-41.
  7. Page E, Winterfield J, Goings G, Bastawrous A, Upshaw-Earley J, et al. (1998) Water channel proteins in rat cardiac myocyte caveolae: osmolarity-dependent reversible internalization. Am J Physiol Heart Circ Physiol 274:H1988-H2000.
  8. Ding FB, Yan YM, Huang JB, Mei J, Zhu JQ, et al. (2013) The involvement of AQP1 in heart oedema induced by global myocardial ischemia. Cell Biochem Funct 31: 60-64.
  9. Yan Y, Huang J, Ding F, Mei J, Zhu J, et al. (2013) Aquaporin 1 plays an important role in myocardial edema caused by cardiopulmonary bypass surgery in goat. Int J Mol Med 31: 637-643.
  10. Rutkovskiy A, Bliksøen M, Hillestad V, Amin M, Czibik G, et al. (2013) Aquaporin-1 in cardiac endothelial cells is downregulated in ischemia, hypoxia and cardioplegia. J Mol Cell Cardiol 56: 22-33.
  11. Ran X, Wang H, Chen Y, Zeng Z, Zhou Q, et al. (2010) Aquaporin-1 expression and angiogenesis in rabbit chronic myocardial ischemia is decreased by acetazolamide. Heart Vessels 25: 237-247.
  12. Rutkovskiy A, Mariero LH, Nygård S, Stensløkken KO, Valen G, et al. (2012) Transient hyperosmolality modulates expression of cardiac aquaporins. Biochem Biophys Res Commun 425: 70-75.
  13. Netti VA, Vatrella MC, Chamorro MF, Rosón MI, Zotta E, et al. (2014) Comparison of cardiovascular aquaporin-1 changes during water restriction between 25- and 50-day-old rats. Eur J Nutr 53: 287-295.
  14. Cheng YS, Tang YQ, Dai DZ, Dai Y (2012) AQP4 knockout mice manifest abnormal expressions of calcium handling proteins possibly due to exacerbating pro-inflammatory factors in the heart. Biochem Pharmacol 83: 97-105.
  15. Rutkovskiy A, Stensløkken KO, Mariero LH, Skrbic B, Amiry-Moghaddam M, et al. (2012) Aquaporin-4 in the heart: expression, regulation and functional role in ischemia. Basic Res Cardiol 107: 280.
  16. Shalaby A, Mennander A, Rinne T, Oksala N, Aanismaa R, et al. (2011) Aquaporin-7 expression during coronary artery bypass grafting with diazoxide. Scand Cardiovasc J 45: 354-359.
Citation: Ozu M (2014) On the Role of Aquaporins in Myocardial Injury. Biochem Pharmacol 3:e155.

Copyright: © 2014 Ozu M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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