Work

Pulmonary Arterial Stiffness: An Early and Pervasive Driver of Pulmonary Arterial Hypertension

Year: 2018

Type: article

Abstract: Pulmonary arterial hypertension (PAH) is a historically neglected and highly morbid vascular disease that leads to right heart failure and, in some cases, death. The molecular origins of this disease have been poorly defined, and as such, current pulmonary vasodilator therapies do not cure or reverse this disease. Although extracellular matrix (ECM) remodeling and pulmonary arterial stiffening have long been associated with end-stage PAH, recent studies have reported that such vascular stiffening can occur early in pathogenesis. Furthermore, there is emerging evidence that ECM stiffening may represent a key first step in pathogenic reprogramming and molecular crosstalk among endothelial, smooth muscle, and fibroblast cells in the remodeled pulmonary vessel. Such processes represent the convergence of activation of a number of specific mechanoactivated signaling pathways, microRNAs, and metabolic pathways in pulmonary vasculature. In this review, we summarize the contemporary understanding of vascular stiffening as a driver of PAH, its mechanisms, potential therapeutic targets and clinical perspectives. Of note, early intervention targeting arterial stiffness may break the vicious cycle of PAH progression, leading to outcome improvement which has not been demonstrated by current vasodilator therapy.

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2018.00204

Authors: Wei Sun, Stephen Y. Chan

Institutions: University of Pittsburgh, University of Pittsburgh Medical Center

Language: English

Topic: Pulmonary Hypertension Research and Treatments

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801