Effect of pulmonary hypertension due to left heart disease on gene expression in pulmonary arteries
Pulmonary hypertension worsens outcome in left heart disease. Stiffening of the pulmonary artery may drive this pathology by increasing right ventricular dysfunction and lung vascular remodeling. We showed that pulmonary arteries from patients with left heart disease are characterized by increased stiffness that correlates with impaired pulmonary hemodynamics. Pulmonary arteries in left heart disease patients with pulmonary hypertension were characterized by degradation of elastic fibers paralleled by an accumulation of fibrillar collagens. We utilized RNA sequencing to identify differentially expressed genes regulating extracellular matrix remodeling in pulmonary arteries of left heart disease patients with or without pulmonary hypertension, in comparison to healthy-heart donor controls. As such we identified that transcriptional deregulation of extracellular matrix constituents and their regulators precedes clinical pulmonary hypertension, and therefore might be a pathomechanism that drives pulmonary arterial remodeling and stiffening in left heart disease. Overall design: To identify genes that are differentially expressed in pulmonary arteries of left heart disease patients without or with pulmonary hypertension (LHD w/o PH or PH-LHD respectively), in comparison to healthy-heart controls (donor), human pulmonary trunk samples were collected during heart transplantation and snap-frozen in liquid nitrogen, followed by TRIzol-RNA extraction and bulk RNA sequencing.