From hypertension to heart failure
Magyar Klára, Deres László, Gál Roland, Riba Ádám, Habon Tamás, Tóth Kálmán, Halmosi Róbert
Pécsi Tudományegyetem, Klinikai Központ, I. sz. Belgyógyászati Klinika, Pécs
Hypertension is an increasing health problem worldwide especially among the elderly. Its therapeutical importance is indicated by the caused organ damages like hypertensive heart disease (HHD) and heart failure with the subsequent higher morbidity and mortality in the population. In HHD ventricular hypertrophy develops as a compensatory mechanism for pressure overload but as the left ventricular compliance decreases, the process can transform into heart failure with firstly preserved and then into reduced ejection fraction (HFpEF, HFrEF). The main characteristics of underlying mechanisms involve cardiomyocyte growth, vessel changes, increased collagen production in all of which several mechanical stress induced neurohumoral agents, signal transduction pathways are involved.
Occasionally, patients are not able to tolerate antihypertensive medication because of side effects, drug intolerance or interactions thus it is more difficult to reach the target blood pressure values. Therefore there are several efforts to complete the existing therapeutical possibilities against the development of organ damages like inhibition of Rho/ROCK pathway, regulation of ROS formation, influence on mitochondrial biogenesis and enhancing recombinant adenovirus hepatocyte growth factor gene.
Hypertension induced oxidative stress causes DNA breaks producing the activation of nuclear poly(ADP-ribose) polymerase-1 (PARP) enzyme that leads to energy depletion and unfavorable modulation of different kinase cascades. PARP activation promotes the development of HHD, and its transition to heart failure. Therefore inhibition of PARP-enzyme offers another new therapeutical approach among hypertensive patients. The purpose of this review is to give a comprehensive summary about the most significant mechanisms in HHD and an insight into new potential therapies.