Na⁺/H⁺ exchanger and cardiac hypertrophy

Reactive cardiac hypertrophy (CH) is an increase in heart mass in response to hemodynamic overload. Exercise-induced CH emerges as an adaptive response with improved cardiac function, in contrast to pathological CH that represents a risk factor for cardiovascular health. The Na⁺/H⁺ exchanger (NHE-1) is a membrane transporter that not only regulates intracellular pH but also intracellular Na⁺ concentration. In the scenario of cardiovascular diseases, myocardial NHE-1 is activated by a variety of stimuli, such as neurohumoral factors and mechanical stress, leading to intracellular Na⁺ overload and activation of prohypertrophic cascades. NHE-1 hyperactivity is intimately linked to heart diseases, including ischemia-reperfusion injury, maladaptive CH and heart failure. In this review, we will present evidence to support that the NHE-1 hyperactivity constitutes a "switch on/off" for the pathological phenotype during CH development. We will also discuss some classical and novel strategies to avoid NHE-1 hyperactivity, and that are therefore worthwhile to improve cardiovascular health.