Background: 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.
Methods: 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.
Results: 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
Conclusion: 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