Pulmonary arterial hypertension: pathogenesis and clinical management

Area of Science:

• Cardiovascular Medicine
• Pulmonary Medicine
• Cell Biology

Background:

• Pulmonary arterial hypertension (PAH) is a severe condition characterized by increased pulmonary artery pressure, leading to vascular remodeling, vasoconstriction, and fibrosis.
• Abnormalities in vascular cells and inflammatory cells, alongside genetic factors like BMPR2 mutations and epigenetic dysregulation, drive PAH pathogenesis.
• Mitochondrial dysfunction and a Warburg metabolic state contribute to uncontrolled cell proliferation and apoptosis resistance in PAH.

Purpose of the Study:

• To review the epidemiology, pathogenesis, diagnosis, and treatment of pulmonary arterial hypertension (PAH).
• To summarize current understanding of the molecular and cellular mechanisms underlying PAH.
• To evaluate the efficacy of existing PAH therapies and identify unmet needs.

Main Methods:

• Literature review of epidemiological data, pathogenetic mechanisms, diagnostic criteria, and therapeutic strategies for PAH.
• Analysis of cellular and molecular abnormalities in pulmonary vasculature and systemic inflammation in PAH.
• Synthesis of information on genetic factors, epigenetic modifications, and metabolic derangements in PAH.

Main Results:

• PAH involves dynamic and structural obstruction of pulmonary vasculature, driven by cellular dysfunction and inflammation.
• Genetic (BMPR2 mutations) and epigenetic factors contribute to aberrant signaling pathways, promoting cell proliferation and apoptosis resistance.
• Current PAH therapies improve functional capacity but do not significantly reduce mortality, indicating a need for treatments addressing core pathogenetic features.

Conclusions:

• PAH is a complex disease involving vascular remodeling, abnormal cell proliferation, and inflammatory processes.
• Despite advances, current treatments offer limited survival benefits, underscoring the urgent need for novel therapeutic approaches targeting the underlying pathogenesis of PAH.
• Further research into the molecular mechanisms of PAH is crucial for developing more effective treatments and improving patient outcomes.