Proteinase-activated Receptor 1 and 2 under Hypoxic Stress

Abstract

Patients with sleep-disordered breathing exhibit intermittent hypoxia that causes increased oxidative stress, accelerates atherosclerosis, and pulmonary hypertension, resulting in life-threatening arrhythmias and congestive heart failure. Hypoxic stress caused by intermittent hypoxia might be involved in the pathophysiology of many cardiovascular dis¬ eases, especially those involving atrial fibrillation, for which anti-coagulant therapy may be recommended. In this study, the inhibition of proteinase-activated receptor (PAR) 1/2 significantly reduced oxidative stress and fibrosis while suppressing the activation of MAPK or Smad pathways and the gene expression of molecules responsible for the pathways in the myocardium, consequently attenuating hypoxia-mediated cardiomyocyte hypertrophy. These findings suggest that the inhibition of P A R 1 /2 could be a novel potential treatment option to prevent cardiac remodeling in patients with sleep apnea syndrome and atrial ibrillation or chronic thromboembolic pulmonary hypertension.