Capillaries as a Therapeutic Target for Heart Failure.

Prognosis of heart failure remains poor, and it is urgent to find new therapies for this critical condition. Oxygen and metabolites are delivered through capillaries; therefore, they have critical roles in the maintenance of cardiac function. With aging or age-related disorders, capillary density is reduced in the heart, and the mechanisms involved in these processes were reported to suppress capillarization in this organ. Studies with rodents showed capillary rarefaction has causal roles for promoting pathologies in failing hearts. Drugs used as first-line therapies for heart failure were also shown to enhance the capillary network in the heart. Recently, the approach with senolysis is attracting enthusiasm in aging research. Genetic or pharmacological approaches concluded that the specific depletion of senescent cells, senolysis, led to reverse aging phenotype. Reagents mediating senolysis are described to be senolytics, and these compounds were shown to ameliorate cardiac dysfunction together with enhancement of capillarization in heart failure models. Studies indicate maintenance of the capillary network as critical for inhibition of pathologies in heart failure.