title: Lung Capillary Stress Failure and Arteriolar Remodelling in Pulmonary Hypertension Associated with Left Heart Disease (Group 2 PH).
abstract: Left heart diseases (LHD) represent the most prevalent cause of pulmonary hypertension (PH), yet there are still no approved therapies that selectively target the pulmonary circulation in LHD. The increase in pulmonary capillary pressure due to LHD is a triggering event leading to physical and biological alterations of the pulmonary circulation. Acutely, mechanosensitive endothelial dysfunction and increased capillary permeability combined with reduced fluid resorption lead to the development of interstitial and alveolar oedema. From repeated cycles of such capillary stress failure originate more profound changes with pulmonary endothelial dysfunction causing increased basal and reactive pulmonary vascular tone. This contributes to pulmonary vascular remodelling with increased arterial wall thickness, but most prominently, to alveolar wall remodelling characterized by myofibroblasts proliferation with collagen and interstitial matrix deposition. Although protective against acute pulmonary oedema, alveolar wall thickening becomes maladaptive and is responsible for the development of a restrictive lung syndrome and impaired gas exchanges contributing to shortness of breath and PH. Increasing awareness of these processes is unraveling novel pathophysiologic processes that could represent selective therapeutic targets. Thus, the roles of caveolins, of the intermediate myofilament nestin and of endothelial calcium dyshomeostasis were recently evaluated in pre-clinical models. The pathophysiology of PH due to LHD (group II PH) is distinctive from other groups of PH. Therefore, therapies targeting PH due to LHD must be evaluated in that context.
authors.affiliation: Research Center, Montreal Heart Institute, Montreal, QC, Canada; Département de Médecine, Université de Montréal, Montréal, QC, Canada.
authors.forename: Nour R
authors.initials: NR
authors.lastname: Dayeh
authors.affiliation: Research Center, Montreal Heart Institute, Montreal, QC, Canada; Département de Physiologie, Université de Montréal, Montréal, QC, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ledoux
authors.affiliation: Research Center, Montreal Heart Institute, Montreal, QC, Canada; Département de Médecine, Université de Montréal, Montréal, QC, Canada; Département de Physiologie, Université de Montréal, Montréal, QC, Canada. Electronic address: dupuisj@me.com.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Dupuis
mesh_terms: D002196:Capillaries / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D018384:Oxidative Stress; D011652:Pulmonary Circulation / Q000502:physiology; D066253:Vascular Remodeling / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000150:complications* / Q000503:physiopathology
keywords: Heart failure; Lung remodelling; Pathophysiology; Pulmonary hypertension; Vascular endothelium