Pulmonary hypertension: pathophysiology and signaling pathways

Area of Science:

• Cardiovascular Medicine
• Pulmonary Medicine
• Cellular Biology

Background:

• Pulmonary hypertension (PH) is a disease of the pulmonary vasculature leading to right ventricular (RV) dysfunction.
• Key features include intimal thickening, hypertrophy, and fibrosis in pulmonary arterioles, with plexogenic lesions in pulmonary arterial hypertension (PAH).
• Current treatments target vasodilation but do not reverse vascular remodeling, highlighting the need for deeper mechanistic understanding.

Purpose of the Study:

• To review current insights into PH pathophysiology and disease mechanisms.
• To discuss novel cell signaling pathways implicated in PH.
• To explore the roles of microRNAs and mitochondrial dysfunction in the PH phenotype.

Main Methods:

• Literature review of PH pathophysiology.
• Analysis of cell signaling pathways involved in vascular remodeling.
• Discussion of molecular mechanisms including microRNAs and mitochondrial dysfunction.

Main Results:

• PH involves pathological cell signaling in the pulmonary arteriole-RV axis, increasing resistance and causing RV dysfunction.
• Severe remodeling, including plexogenic lesions, can obliterate pulmonary arterioles.
• RV remodeling extent correlates with symptom severity and poor prognosis.

Conclusions:

• Determining molecular mechanisms driving pulmonary vascular remodeling is crucial for therapeutic development.
• Pathways promoting apoptosis-resistant proliferation, altered bioenergetics, and abnormal injury responses are key targets.
• MicroRNAs and mitochondrial dysfunction are implicated in the development of the PH phenotype.