title: Pulmonary Arterial Stiffness: Toward a New Paradigm in Pulmonary Arterial Hypertension Pathophysiology and Assessment.
abstract: Stiffening of the pulmonary arterial bed with the subsequent increased load on the right ventricle is a paramount feature of pulmonary hypertension (PH). The pathophysiology of vascular stiffening is a complex and self-reinforcing function of extracellular matrix remodeling, driven by recruitment of circulating inflammatory cells and their interactions with resident vascular cells, and mechanotransduction of altered hemodynamic forces throughout the ventricular-vascular axis. New approaches to understanding the cell and molecular determinants of the pathophysiology combine novel biopolymer substrates, controlled flow conditions, and defined cell types to recapitulate the biomechanical environment in vitro. Simultaneously, advances are occurring to assess novel parameters of stiffness in vivo. In this comprehensive state-of-art review, we describe clinical hemodynamic markers, together with the newest translational echocardiographic and cardiac magnetic resonance imaging methods, to assess vascular stiffness and ventricular-vascular coupling. Finally, fluid-tissue interactions appear to offer a novel route of investigating the mechanotransduction processes and disease progression.
authors.affiliation: University of Colorado Anschutz Medical Campus, 12700 E. 19th Avenue, Box B131, Aurora, CO, 80045, USA. Michal.Schafer@ucdever.edu.
authors.forename: Michal
authors.initials: M
authors.lastname: Schäfer
authors.affiliation: University of Colorado Anschutz Medical Campus, 12700 E. 19th Avenue, Box B131, Aurora, CO, 80045, USA. Cynthia.Myers@ucdenver.edu.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Myers
authors.affiliation: University of Colorado Anschutz Medical Campus, 12700 E. 19th Avenue, Box B131, Aurora, CO, 80045, USA. Dale.Brown@ucdenver.edu.
authors.forename: R Dale
authors.initials: RD
authors.lastname: Brown
authors.affiliation: University of Colorado Anschutz Medical Campus, 12700 E. 19th Avenue, Box B131, Aurora, CO, 80045, USA. Maria.Frid@ucdenver.edu.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Frid
authors.affiliation: 427 University of Colorado Boulder, 1111 Engineering Drive, ECME 114, Boulder, CO, 80309, USA. WTan@colorado.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.affiliation: University of Colorado Anschutz Medical Campus, 12700 E. 19th Avenue, Box B131, Aurora, CO, 80045, USA. Kendall.Hunter@ucdenver.edu.
authors.forename: Kendall
authors.initials: K
authors.lastname: Hunter
authors.affiliation: University of Colorado Anschutz Medical Campus, 12700 E. 19th Avenue, Box B131, Aurora, CO, 80045, USA. Kurt.Stenmark@ucdenver.edu.
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Stenmark
mesh_terms: D004452:Echocardiography; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D011651:Pulmonary Artery; D059289:Vascular Stiffness
keywords: Extracellular matrix; Imaging; Inflammation; Macrophage; Pulmonary hypertension; Vascular stiffening