THE ROLE OF COLLAGEN SYNTHESIS IN VENTRICULAR AND VASCULAR ADAPTATION TO HYPOXIC PULMONARY HYPERTENSION

摘要

Pulmonary hypertension (PH) is a debilitating disease that affects millions of Americans. Most research to date has focused on the deleterious effects of PH within the small vessels of the lungs that determine resistance. A relatively recent focus of PH is on the large pulmonary arteries (PAs) that provide compliance. Loss of compliance in these arteries, or arterial stiffening, is an excellent predictor of mortality in PH [1], which is most often caused by right ventricular (RV) hypertrophy and failure [2]. A common model of PH is hypoxic pulmonary hypertension (HPH), which initially causes vasoconstriction of distal arterioles in the lungs, and chronically causes proximal PA stiffening. Previous work has demonstrated that collagen is a key contributor to proximal PA stiffening [3]. Agents that impair the synthesis of collagen have been shown to limit the severity of PH and RV hypertrophy [4].