Researchers showed an association between high levels of extracellular matrix (ECM) related proteins and poor prognosis in patients with pulmonary arterial hypertension (PAH), as published in Pulmonary Circulation.
Arvidsson et al studied the serum levels of 14 ECM-related proteins and correlated them with the clinical findings evaluated in the European Society of Cardiology and European Respiratory Society (ESC/ERS) risk assessment tool for 1-year mortality.
They found that higher plasma levels of all 4 different matrix metalloproteinases (MMPs) were associated with worse survival rates in transplant-free patients. Similar results were obtained with the tissue inhibitor of metalloproteinase 4 (TIMP-4) and perlecan.
Matrix metalloproteinase 2 (MMP-2) was further related with 3 out of 9 ESC/ERS risk score items such as mean right atrial pressure, N-terminal pro-brain natriuretic peptide (NT-proBNP), and 6 Minute Walking Distance scores. Hazard ratio with a 95% CI was individually calculated for all ECM-related proteins.
“The present study indicates that high levels of MMP-2, perlecan and TIMP-4 are associated with poor survival in PAH. High plasma MMP-2, correlated with poor prognosis in PAH,” the authors wrote.
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Moreover, only glypican-1 was found to be more elevated in patients with PAH associated with connective tissue diseases vs idiopathic or familial PAH. It was also the only variable with higher serum levels prior to treatment initiation, and despite being the most promising marker, MMP-2 did not exhibit such variations after treatment.
Noting that the physiopathology of PAH includes the continuous expansion of the ECM surrounding the pulmonary vessels that will later promote vascular fibrosis and diminished compliance, the authors hypothesized that ECM-related proteins might be potential biomarkers for PAH prognosis. Currently, NT-proBNP is vastly used as a biomarker for disease severity, and ECM-related proteins may reflect a more precise mortality predictor.
“For instance, a patient with otherwise low-risk or intermediate-risk characteristics, that would display a biomarker profile of poor prognosis could benefit from an earlier and more aggressive escalation of PAH specific treatment,” they concluded.
Arvidsson M, Ahmed A, Säleby J, Hesselstrand R, Rådegran G. Plasma matrix metalloproteinase 2 is associated with severity and mortality in pulmonary arterial hypertension. Pulm Circ. Published online January 24, 2022. doi:10.1002/pul2.12041