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February 17, 2021AJP Lung Cellular and Molecular PhysiologyOpen Access

Platelets from IPAH patients demonstrated reduced expression of G protein αs, increased PKA type II isoforms, reduced sGC subunits, and increased PDE5A, with significant inter-patient variation in sGC levels among 38 patients.

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Why the study?

Long-term mortality in IPAH remains high with treatment response heterogeneity, and platelets show metabolic shifts and activation defects that may reflect disease-specific abnormalities.

Do platelets from patients with IPAH show disease-specific abnormalities in vasoactive signaling pathways compared to healthy controls?

Population

Patients with IPAH, including a cohort of 38 unique patients, and healthy controls

Comparison

Patients with IPAH vs healthy controls

Design

Case-control proteomic study

Authors

KAKulwant S. AulakSASami Al AbdiLLLing Li

Discussion

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Overview

Platelets may offer an accessible readout of IPAH pathway defects; leaves open whether they can personalize therapy amid response heterogeneity.

Key Points

  • To determine whether circulating platelets exhibit disease-specific signaling abnormalities that reflect systemic pathology and inform therapeutic decisions in idiopathic pulmonary arterial hypertension.
  • Performed proteomic profiling to evaluate differential protein expression in platelets from patients with idiopathic pulmonary arterial hypertension (IPAH) relative to healthy controls.
  • Quantified expression and enzymatic activity of key nitric oxide pathway components in platelets from a validation cohort of 38 unique patients with IPAH.
  • Platelets from IPAH patients showed downregulation of G protein αs and upregulation of type II cAMP-dependent protein kinase regulatory subunits, consistent with reduced prostacyclin pathway activation.
  • Proteomic analysis detected decreased soluble guanylate cyclase (sGC) subunits alongside increased phosphodiesterase type 5 A (PDE5A) expression, compromising nitric oxide signaling.
  • Validation in 38 patients with IPAH revealed marked inter-individual heterogeneity in the expression levels and specific enzymatic activity of sGC.

Structured PICO

Do platelets from patients with IPAH show disease-specific abnormalities in vasoactive signaling pathways compared to healthy controls?

P
Population
Patients with idiopathic pulmonary arterial hypertension (IPAH) (n=38 in the secondary cohort) and healthy controls.
I
Intervention
Proteomic analysis of platelets
C
Comparator
Healthy controls
O
Outcome
Protein expression changes in platelets, specifically in the prostacyclin and nitric oxide pathwayssurrogate

Platelets from patients with IPAH exhibit characteristic abnormalities in prostacyclin and nitric oxide signaling pathways, which may serve as ex vivo biomarkers to guide personalized therapy.

Cite This Study

Aulak et al. (2021) studied this question.

synapsesocial.com/papers/6a7fac93c32ce294b5d76e57https://doi.org/10.1152/ajplung.00500.2020
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Identification of potential biomarkers for idiopathic pulmonary arterial hypertension using single-cell and bulk RNA sequencing analysis2024 · 6 citations
  2. 2Prognostic Role of Platelets in Pulmonary Arterial Hypertension2025
  3. 3The Role of Platelets in Pulmonary Hypertension: From Activation to Pulmonary Vascular Remodeling—A Review Article2026
  4. 4Platelet mitofusin-1 mediates endothelial cell dysfunction in pulmonary arterial hypertension via the NLRP3 inflammasome and interleukin-1B2025
  5. 5Coronary pathophysiology in idiopathic pulmonary arterial hypertension: A systems medicine study.2026