Epigenetic Inheritance Underlying Pulmonary Arterial Hypertension.

Area of Science:

• Pulmonary and cardiovascular research
• Molecular biology and epigenetics
• Network medicine and bioinformatics

Background:

• Pulmonary arterial hypertension (PAH) is characterized by cellular changes like proliferation and apoptosis resistance, driven by the Warburg effect and mitochondrial fission.
• Current PAH therapies primarily focus on vasodilation and anticoagulation, failing to address the underlying cellular phenotype alterations.
• Epigenetic modifications, particularly those induced by hypoxia and potentially transgenerational, are increasingly recognized as key drivers of vascular remodeling in PAH.

Purpose of the Study:

• To review current clinical and epigenetic factors contributing to PAH vascular remodeling across different life stages.
• To explore the application of network medicine strategies and molecular network-based algorithms in understanding PAH pathobiology.
• To propose an integrated network-based approach for discovering novel biomarkers and therapeutic targets in PAH.

Main Methods:

• Literature review focusing on clinical evidence, epigenetic changes, and network medicine approaches in PAH.
• Discussion of molecular network-based algorithms for dissecting PAH pathobiology from morphogenesis to disease onset.
• Conceptual framework for an integrated network-based program for clinical disease gene discovery.

Main Results:

• The Warburg effect and mitochondrial fission are critical in PAH phenotype alterations.
• Epigenetic changes, unlike genetic mutations, are pharmacologically reversible and represent a promising therapeutic avenue.
• Network medicine strategies and algorithms are crucial for dissecting complex PAH molecular mechanisms.

Conclusions:

• Targeting reversible epigenetic changes offers a novel therapeutic strategy for PAH.
• Network medicine and integrated gene discovery programs can identify new biomarkers and therapeutic targets for PAH.
• A precision medicine approach, informed by network analysis, is essential for redefining and treating PAH effectively.