Wall stress and shear stress are drivers of adaptive and maladaptive processes resulting in endothelial dysfunction, smooth muscle hypertrophy, and inflammation. Many of these mediators of endothelial function in PH-LHD that have effects both systemically and locally. eNOS: endothelial nitric oxide synthase, IR:insulin receptor, NO: nitric oxide, ANP: atrial natriuretic peptide, TNF-α:Tumor necrosis factor alpha, COX: cyclooxygenase, PGI2:Prostaglandin I2, IPR: Prostacyclin I2 receptor, TXA2: thromboxane A2, TPR: Thromboxane A2 receptor, ET-1: endothelin-1, ETA: Endothelin receptor A, 5-HT: serotonin, 5-HTR: serotonin receptor, IL-6: Interleukin-6, CRP: C-reactive protein