This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "pulmonary_vascular_remodeling#Obstructive Pulmonary Vascular Remodeling"). The module defines the expected pathophysiology structure; conforming nodes in disorder files should include the corresponding cell types, biological processes, and causal edges, specialized to their disease context. Key disorder-specific substitutions: heritable PAH substitutes a BMPR2 loss-of-function lesion at the trigger node; idiopathic PAH substitutes acquired endothelial injury; connective-tissue-disease-associated PAH (e.g., systemic sclerosis) substitutes immune/inflammatory endothelial injury. The pulmonary artery endothelial cell and pulmonary artery smooth muscle cell are the conserved central cell types.
Pulmonary Endothelial Dysfunction and Impaired BMP Signaling
trigger
The initiating lesion is injury to and dysfunction of pulmonary arterial endothelial cells, with impaired bone morphogenetic protein (BMP) signaling (loss-of-function BMPR2 mutations in heritable PAH, acquired suppression in idiopathic and associated PAH). Dysfunctional endothelium loses its ability to produce vasodilatory mediators such as nitric oxide and prostacyclin while favoring vasoconstrictors such as endothelin-1, and undergoes hyperproliferation with early apoptosis followed by enrichment of apoptosis-resistant cells. This endothelial trigger generalizes across heritable, idiopathic, and connective-tissue-disease-associated PAH.
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Pulmonary Artery Smooth Muscle Cell Proliferation and Vasoconstriction
Pulmonary Artery Smooth Muscle Cell Proliferation and Vasoconstriction
amplifier
Paracrine signals from the dysfunctional endothelium drive a cancer-like pro-proliferative, anti-apoptotic switch in pulmonary artery smooth muscle cells (PASMCs), together with sustained vasoconstriction. PASMCs acquire migratory capacity and resistance to apoptosis, increasing medial cellularity. This amplifying step is conserved across PAH subtypes regardless of the specific initiating endothelial injury.
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Obstructive Pulmonary Vascular Remodeling
Obstructive Pulmonary Vascular Remodeling
central effector
Sustained PASMC proliferation, neointima formation, and endothelial dysregulation remodel the pulmonary arterial wall, producing medial and adventitial hypertrophy, muscularization of previously nonmuscular peripheral arteries, and intimal and plexiform lesions that obliterate the lumen of small pulmonary arteries. This structural obstruction is the central effector of the module and is conserved across PAH subtypes.
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Increased Pulmonary Vascular Resistance
Increased Pulmonary Vascular Resistance
effector
Structural obstruction and sustained vasoconstriction of the small pulmonary arteries increase pulmonary vascular resistance. The combination of dynamic (vasoconstrictive) and fixed (remodeling) obstruction raises the resistance the right ventricle must pump against.
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Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension
consequence
The convergent consequence is a sustained elevation of pulmonary arterial pressure. The increased resistance imposes a chronic pressure overload on the right ventricle, causing right ventricular hypertrophy and, in many patients, maladaptive remodeling that progresses to right ventricular failure and premature death. This is the named clinical phenotype (HP:0002092; MONDO:0005149).