Discovery of aquaporins nearly 30 years ago has substantially broadened our understanding of cellular water transport. Aquaporins are expresed in the majority of tissues where filtration and separation of fluids takes place. Aquaporins have been extensively studied in the brain, kidney, eyes and other organs, but cardiac aquaporins have not been brought into focus yet. Cardiac aquaporins may potentially influence formation and resolution of tissue edema which is an integral part of ischemic damage. We studied expression of AQP1 and -4 in the mouse and human heart. AQP1 was found expressed exclusively in endothelial cells, both on basal and apical membranes, and in submembrane domain – in caveolae. AQP4, conversely, was found only in cardiomyocytes. Both proteins were uniformly distributed over the cell membranes. Both aquaporins were downregulated on mRNA and protein levels by acute myocardial ischemia and chronic exposure to normobaric hypoxia. At the same time, plasma hyperosmolarity regulated them differentially. AQP1 expression was induced, while AQP4 was inhibited. AQP4 ablation was found to decrease cardiac ischemic injury both in the model of isolated heart perfusion and induced infarction in vivo. The effect may partially be explained by a minor reduction in myocardial water accumulation, however, survival cell signaling pathways may also be involved.

Conclusion: 

AQP1 and -4 have different cellular localization in the heart. Their expression appears to decrease during ischemia and hypoxia and changes in opposite directions in response to hyperosmolarity. AQP4 contributes to myocardial ischemic injury, however, the precise mechanisms are still unclear.