Treatment-related biomarkers in pulmonary hypertension.

Swaminathan, Aparna C

Dusek, Alex C

McMahon, Tim J

United States

2015-11-23T14:23:15Z

2015-06

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.

http://www.ncbi.nlm.nih.gov/pubmed/25611885

1535-4989

https://hdl.handle.net/10161/10918

eng

American Thoracic Society

Am J Respir Cell Mol Biol

10.1165/rcmb.2014-0438TR

biomarker

endothelin

nitric oxide

right ventricle

Animals

Antihypertensive Agents

Atrial Natriuretic Factor

Biomarkers

Cyclic AMP

Cyclic GMP

Endothelin-1

Humans

Hypertension, Pulmonary

Natriuretic Peptide, Brain

Nitric Oxide

S-Nitrosothiols

Treatment Outcome

Treatment-related biomarkers in pulmonary hypertension.

Journal article

Swaminathan, Aparna C|0000-0002-0003-9971

http://www.ncbi.nlm.nih.gov/pubmed/25611885

663

673

6

Clinical Science Departments

Duke

Medicine

Medicine, Pulmonary, Allergy, and Critical Care Medicine

School of Medicine

Published

52