Fine mapping of the pulmonary artery matrisome in a large animal model of hypoxia-induced pulmonary hypertension

ABSTRACT: Pulmonary hypertension (PH) is a progressive disease with a high mortality rate, usually as a result of right heart failure. The pulmonary vasculature in PH is characterized by remodeling and stiffening, potentially with luminal obstruction, driven by enhanced cell proliferation/survival versus cell death, chronic inflammation, and altered extracellular matrix (ECM), with an increase in vascular fibrosis. Given the poorly understood biochemical nature of pulmonary vascular remodeling, we evaluated the ECM and ECM-associated protein composition of the main pulmonary artery (MPA), distal pulmonary arteries (DPA) distal whole lung (DWL) of acute hypoxia-driven PH (in a young bovine calf model) using high-resolution mass spectrometry. Significant differences in the proteomic signatures were observed in the three vascular/tissue sites. Alterations included a strong immune response and wound repair signature including several proteins from the coagulation cascade and markers of a provisional matrix. These findings support a role for disease propagation that proceeds through a wound-healing trajectory with a strong hemostasis and provision matrix in the MPA, to a more destructive remodeling with higher turnover in the most distal capillaries. This data provides insight into short-term remodeling that results in robust biomechanical manifestation of PH and initiates a resolvable disease trajectory when hypoxic insult is removed.

INSTRUMENT(S):

ORGANISM(S): Bos Taurus (bovine)

TISSUE(S): Blood Plasma

DISEASE(S): Pulmonary Hypertension

SUBMITTER: Kirk Hansen  

LAB HEAD: Kirk Hansen

PROVIDER: PXD046794 | Pride | 2025-12-08

REPOSITORIES: Pride