Related Experiment Videos
Biomarkers in Pulmonary Vascular Disease: Gauging Response to Therapy
Timothy J McMahon1, Nathan S Bryan2
1Duke University, Durham, North Carolina.
Abstract:
Biomarkers are increasingly being investigated in the treatment of pulmonary vascular disease. In particular, the signaling pathways targeted by therapies for pulmonary arterial hypertension provide biomarkers that potentially can be used to guide therapy and to assess clinical response as an alternative to invasive procedures such as right-sided cardiac catheterization. Moreover, the growing use of combination therapy for both the initial and subsequent treatment of pulmonary arterial hypertension highlights the need for biomarkers in this treatment approach. Currently approved therapies for pulmonary arterial hypertension target 3 major signaling pathways: the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway, the endothelin pathway, and the prostacyclin pathway. Although the main biomarker used in practice and evaluated in clinical trials is N-terminal pro-brain natriuretic peptide, other putative biomarkers include the endogenous nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine, NO metabolites including S-nitrosothiols and nitrite, exhaled NO, endothelins, cyclic guanosine monophosphate, cyclic adenosine monophosphate, and atrial natriuretic peptide. This review describes accessible biomarkers, related to the actual molecules targeted by current therapies, for measuring and predicting response to the individual pulmonary arterial hypertension treatment classes as well as combination therapy.
Insights
Biomarkers for pulmonary arterial hypertension (PAH) can guide therapy and assess treatment response, potentially replacing invasive cardiac catheterization. This review explores accessible biomarkers linked to current PAH therapies, including combination treatments.
Area of Science:
- Pulmonary vascular disease research
- Cardiovascular medicine
- Biomarker discovery
Background:
- Pulmonary arterial hypertension (PAH) treatment relies on targeting specific signaling pathways.
- Combination therapies are increasingly used for PAH, necessitating effective monitoring tools.
- Current monitoring often involves invasive procedures like right-sided cardiac catheterization.
Purpose of the Study:
- To review accessible biomarkers for pulmonary arterial hypertension (PAH).
- To correlate biomarkers with targeted signaling pathways in current PAH therapies.
- To evaluate biomarkers for predicting response to individual and combination PAH treatments.
Main Methods:
- Literature review of current PAH therapies and associated biomarkers.
- Analysis of biomarkers related to nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate, endothelin, and prostacyclin pathways.
- Identification of established and putative biomarkers including N-terminal pro-brain natriuretic peptide, asymmetric dimethylarginine, and NO metabolites.
Main Results:
- N-terminal pro-brain natriuretic peptide is a primary biomarker in PAH clinical practice.
- Other biomarkers investigated include asymmetric dimethylarginine, NO metabolites (S-nitrosothiols, nitrite), exhaled NO, endothelins, cyclic guanosine monophosphate, cyclic adenosine monophosphate, and atrial natriuretic peptide.
- These biomarkers relate to key pathways targeted by PAH therapies.
Conclusions:
- Accessible biomarkers can aid in guiding PAH therapy and assessing treatment efficacy.
- Biomarkers offer a potential alternative to invasive monitoring methods.
- Further research into these biomarkers is crucial for optimizing PAH management, especially with combination therapies.