title: Treatment-related biomarkers in pulmonary hypertension.
abstract: Significant advances in the treatment of pulmonary arterial hypertension (PAH) over the last two decades have led to the introduction of multiple classes of oral therapy, but the disease remains devastating for many patients. Disease progression, in spite of oral monotherapy, is a major problem, and alternative therapy, such as infusion of prostacyclins, is cumbersome and carries considerable potential morbidity. Use of combination oral therapy, including drugs from both the endothelin receptor antagonist and phosphodiesterase-5 inhibitor classes, has increased, and there is some evidence to support this approach. Given the multiple options now available in pulmonary hypertension (PH) therapy, biomarkers to guide treatment decisions could be helpful. Here, we review the evidence for and against the clinical use of molecular biomarkers relevant to PH pathogenesis, emphasizing assayable markers that may also inform more rational selection of agents that influence pathways targeted by treatment. We emphasize the interactive nature of changes in mediators and messengers, such as endothelin-1, prostacyclin, brain natriuretic peptide (which has demonstrated biomarker utility), nitric oxide derivatives, and cyclic guanosine monophosphate, which play important roles in processes central to progression of PAH, such as vascular remodeling, vasoconstriction, and maladaptive right ventricular changes, and are relevant to its therapy. Accordingly, we propose that the identification and use of a molecular biomarker panel that assays these molecules in parallel and serially might, if validated, better inform unique patient phenotypes, prognosis, and the rational selection and titration of combination oral and other therapy in individual patients with PH/PAH.
authors.affiliation: 1 Duke University and Durham Department of Veterans Affairs Medical Centers, Durham, North Carolina; and.
authors.forename: Aparna C
authors.initials: AC
authors.lastname: Swaminathan
authors.forename: Alex C
authors.initials: AC
authors.lastname: Dusek
authors.forename: Tim J
authors.initials: TJ
authors.lastname: McMahon
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D019332:Endothelin-1 / Q000097:blood; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000188:drug therapy; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D026403:S-Nitrosothiols / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D019332:Endothelin-1; D026403:S-Nitrosothiols; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D006152:Cyclic GMP
keywords: biomarker; endothelin; nitric oxide; right ventricle