Cell Death in Pulmonary Arterial Hypertension

Area of Science:

• Cardiovascular Research
• Cell Biology
• Pulmonary Medicine

Background:

• Pulmonary arterial hypertension (PAH) is a severe vascular disease leading to right ventricular hypertrophy and heart failure.
• Cell death mechanisms are crucial for tissue homeostasis and regulating cell proliferation and differentiation.
• Multiple cell death pathways are implicated in the pathogenesis of PAH.

Purpose of the Study:

• To review the diverse cell death mechanisms involved in pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs) in PAH.
• To summarize the roles of these cell death mechanisms, their signaling pathways, effector molecules, and survival/reprogramming factors.
• To consolidate current knowledge on the molecular mechanisms underlying PAH pathogenesis.

Main Methods:

• Literature review of basic and clinical studies on cell death in PAH.
• Analysis of cell death mechanisms including pyroptosis, apoptosis, autophagy, ferroptosis, anoikis, parthanatos, and senescence.
• Focus on the molecular pathways and cellular targets within the pulmonary vasculature.

Main Results:

• Several distinct cell death mechanisms, including pyroptosis, apoptosis, autophagy, ferroptosis, anoikis, parthanatos, and senescence, are closely linked to PAH pathogenesis.
• These mechanisms affect key cell types in PAH, namely PASMCs and PAECs.
• Associated signaling pathways, effector molecules, and regulatory mechanisms influencing cell survival and reprogramming have been identified.

Conclusions:

• Cell death pathways are integral to the molecular mechanisms driving PAH.
• Targeting these specific cell death mechanisms presents potential novel therapeutic strategies for PAH.
• Further research into cell death pathways is essential for advancing PAH prevention and treatment.