Regulation of Na+/K+-ATPase by Estradiol and IGF-1 in Cardio-Metabolic Diseases.
The sodium/potassium- adenosine- triphosphatase (Na+/K+-ATPase) is an important mediator in vasculature tone and contractility, and its abnormal regulation has been implicated in many diseases such as obesity, insulin resistance, diabetes, and hypertension. Decreased Na+/K+-ATPase abundance and its altered isoform expression induce cardiomyocytes death and cardiac dysfunction, possibly leading to the development of myocardial dilation and heart failure. Therefore, the regulation of Na+/K+-ATPase activity/expression could be important in treatment and possible prevention of cardio-metabolic diseases. A number of hormones and environmental factors regulate the function of Na+/K+-ATPase in response to changing cellular requirements. Estradiol and insulin like growth factor-1 (IGF-1) are among potent hormones that positively regulate Na+/K+- ATPase activity or de novo synthesis of α - and β - subunits. Both estradiol and IGF-1 have a huge therapeutic potential in treatment of vasculopathy in cardio-metabolic diseases.



We searched the MEDLINE and PUBMED databases for all English and non-English articles with an English abstract from April 1978 to May 2016. The main data search terms were: Na+/K+-ATPase; estradiol and Na+/K+-ATPase; estradiol, Na+/K+-ATPase and CVS; estradiol, Na+/K+-ATPase and CVD; estradiol, Na+/K+- ATPase and obesity; estradiol, Na+/K+-ATPase and diabetes; estradiol, Na+/K+-ATPase and hypertension; IGF-1; IGF-1 and Na+/K+-ATPase; IGF-1, Na+/K+-ATPase and CVS; IGF-1, Na+/K+-ATPase and CVD; IGF-1, Na+/K+- ATPase and obesity; IGF-1, Na+/K+-ATPase and diabetes; IGF-1, Na+/K+-ATPase and hypertension.



The present review discusses the latest data from animal and human studies which focus on the effects of estradiol and IGF-1 on Na+/K+-ATPase regulation in physiological and pathophysiological conditions in cardiovascular system.



Understanding the molecular mechanisms of estradiol and IGF-1 action on Na+/K+-ATPase in humans, may help resolving outstanding issues and developing new strategies for the protection and treatment of cardiovascular diseases.
Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade, Serbia.
Milan
M
Obradovic
Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade, Serbia.
Julijana
J
Stanimirovic
Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade, Serbia.
Anastasija
A
Panic
Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade, Serbia.
Nikola
N
Bogdanovic
Laboratory of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Mike Petrovica Alasa 12-14, 11000 Belgrade, Serbia.
Emina
E
Sudar-Milovanovic
Faculty of Stomatology, Pancevo, University Business Academy, 21000 Novi Sad, Serbia.
Desanka
D
Cenic-Milosevic
Institute of Nuclear Sciences Vinca, University of Belgrade, Laboratory of Radiobiology and Molecular Genetics, P.O.Box 522, 11000 Belgrade, Serbia.
Esma R
ER
Isenovic
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D000254:Sodium-Potassium-Exchanging ATPase
Sodium potassium adenosine-triphosphatase; cardio-metabolic diseases; estradiol; insulin like growth factor-1