Circulating Biomarkers in Pulmonary Arterial Hypertension: An Update

Abstract

Pulmonary arterial hypertension (PAH) is a rare subtype of group 1 pulmonary hypertension (PH) diseases, characterized by high pulmonary artery pressure leading to right ventricular dysfunction and potential life-threatening consequences. PAH involves complex mechanisms: vasoconstriction, vascular remodeling, endothelial dysfunction, inflammation, oxidative stress, fibrosis, RV remodeling, cellular hypoxia, metabolic imbalance, and thrombosis. These mechanisms are mediated by several pathways, involving molecules like nitric oxide and prostacyclin. PAH diagnosis requires clinical evaluation and right heart catheterization, confirming a value of mPAP ≥ 20 mmHg at rest and often elevated pulmonary vascular resistance (PVR). Even if an early and accurate diagnosis is crucial, PAH still lacks effective biomarkers to assist in its diagnosis and prognosis. Biomarkers could contribute to arousing clinical suspicion and serve for prognosis prediction, risk stratification, and dynamic monitoring in patients with PAH. The aim of the present review is to report the main novelties on new possible biomarkers for the diagnosis, prognosis, and treatment monitoring of PAH.

Keywords: biomarker; diagnosis; pulmonary arterial hypertension; pulmonary hypertension; treatment.

Figure 1

Biomarkers with a possible role in the diagnosis, prognosis, and treatment of PAH. BNP and NTproBNP (bone natriuretic factor and N-terminal pro-B-type natriuretic peptide), ANP (atrial natriuretic peptide), Cys C (cystatin-C), ET-1 (endothelin-1), ADMA (asymmetric dimethylarginine), Urinary cGMP (urinary cyclic guanosine monophosphate), Ang-1 and Ang-2 (angiopoietin-1 and angiopoietin-2), IDO-TMs (indoleamine 2,3-dioxygenase (IDO)-dependent tryptophan metabolites), ST2 (suppression of tumorigenicity 2), IL6, IL8,IL10 (interleukin-6, interleukin-8, interleukin-10), FSTL3 (follistatin-like 3), SNO-Hb (S-nitrosohemoglobin), sCD40L (soluble CD40 ligand), CRP (C-reactive protein), β-NGF, CXCL9, TRAIL (beta nerve growth factor; C-X-C motif chemokine ligand 9; TNF-related apoptosis-inducing ligand), ADM (adrenomedullin), cGMP (cyclic guanosine monophosphate), NO (nitric oxide).