The Na/K ATPase in cardiovascular health and disease

A tiny molecular pump in heart and blood vessel cells is failing to do its job properly, and this failure is driving the muscle thickening, stiffening, and narrowing that underlies heart failure and high blood pressure. The Na/K ATPase (NKA) pump normally maintains the right balance of sodium and potassium inside cells. A regulatory protein called PLM controls this pump. The researchers have found that when this regulation goes wrong, heart muscle cells accumulate too much sodium, and blood vessel cells constrict too tightly. This directly contributes to a common form of heart failure called HFpEF, as well as to hypertension and kidney disease. Current treatments for these conditions are limited, partly because the underlying cellular mechanisms remain poorly understood. This research will map exactly how NKA/PLM regulation breaks down in disease, and will search for molecules that can activate the pump to restore normal function. If successful, it could open the door to a new class of drugs that target the pump directly—something no existing heart failure or hypertension medication does. The work also explores whether naturally occurring steroids that inhibit NKA play a role in cardiorenal disease, which could identify patients who might benefit from different treatment strategies.