Aquaporin Channels in the Heart—Physiology and Pathophysiology

Abstract

Mammalian aquaporins (AQPs) are transmembrane channels expressed in a large variety of cells and tissues throughout the body. They are known as water channels, but they also facilitate the transport of small solutes, gasses, and monovalent cations. To date, 13 different AQPs, encoded by the genes AQP0–AQP12, have been identified in mammals, which regulate various important biological functions in kidney, brain, lung, digestive system, eye, and skin. Consequently, dysfunction of AQPs is involved in a wide variety of disorders. AQPs are also present in the heart, even with a specific distribution pattern in cardiomyocytes, but whether their presence is essential for proper (electro)physiological cardiac function has not intensively been studied. This review summarizes recent findings and highlights the involvement of AQPs in normal and pathological cardiac function. We conclude that AQPs are at least implicated in proper cardiac water homeostasis and energy balance as well as heart failure and arsenic cardiotoxicity. However, this review also demonstrates that many effects of cardiac AQPs, especially on excitation-contraction coupling processes, are virtually unexplored.

Human Aquaporins: Functional Diversity and Potential Roles in Infectious and Non-infectious Diseases

“…Eight AQPs namely AQP1, 3, 4, 5, 7, 9, 10, and 11 are found in cardiovascular system ( Figure 1 ). These AQP homologs located to the heart, endothelial cells, and vascular smooth muscle participate in the transportation of water, glycerol, and lactic acid, which play pivotal roles in cardiac physiology ( Butler et al, 2006 ; Verkerk et al, 2019 ; Montiel et al, 2020 ). Ten AQPs (AQP0, 1, 2, 3, 4, 5, 7, 8, 9, and 11) expressed in male reproductive system ( Figure 1 ) act as water, glycerol and ion channel during various process involved such as spermatogenesis, sperm osmoadaptation, and folliculogenesis ( Day et al, 2014 ; Carrageta et al, 2020 ).…”

“…AQPs mainly facilitate the transmembrane diffusion of water as well as various small solutes and are involved in cellular trafficking and many physiological processes ( Hedfalk et al, 2006 ; Törnroth-Horsefield et al, 2006 ; Azad et al, 2008 ; Törnroth-Horsefield et al, 2010 ; Janosi and Ceccarelli, 2013 ; Kaptan et al, 2015 ; Pelagalli et al, 2016 ; Canessa Fortuna et al, 2019 ). Functionally diverged human AQPs are involved in wide variety of non-infectious diseases including cancer, renal dysfunction, neurological disorder, epilepsy, skin disease, metabolic syndrome, and even cardiac diseases ( Verkman et al, 2008a , b , 2014 ; Verkerk et al, 2019 ). Growing data suggest their possible involvement in cell volume regulating events associated with various non-infectious diseases ( Verkman et al, 2014 ; Pelagalli et al, 2016 ; Meli et al, 2018 ).…”

WITHDRAWN: LPL/AQP7/GPD2 promotes glycerol metabolism under hypoxia and prevents cardiac dysfunction during ischemia.

“…Cardiomyocyte-speci c LPL de ciency enhanced cardiac dysfunction and apoptosis following MI. De ciency of aquaporin 7 (AQP7), a glycerol channel in cardiomyocytes 5,6 , increased the myocardial infarct size and apoptosis in response to ischemia. Ischemic conditions activated glycerol-3phosphate dehydrogenase 2 (GPD2), which converts glycerol-3-phosphate into dihydroxyacetone phosphate to facilitate ATP synthesis from glycerol 7 .…”

Gene Expression Changes of Humans with Primary Mitral Regurgitation and Reduced Left Ventricular Ejection Fraction

“…CRY1 is a human circadian clock gene; and acute myocardial infarction and arrythmias are regulated by circadian clock genes [ 18 ]. AQP7P3 is the main aquaglyceroporin in the heart situated in between the capillary lumen and interstitial space that acts as a glycerol facilitator, and its dysfunction can lead to cardiac hypertrophy and death [ 19 ]. Finally, elevated IGFBP2 inhibits IGF-1, which regulates LV dysfunction and is a biomarker for predicting heart failure [ 20 ].…”