Figures
- Figure 1.
The key pathological mechanisms underlying vascular changes in pulmonary hypertension (PH). Potential new therapies for PH are also indicated. AEC: alveolar epithelial cell; vWF: von Willebrand factor; TXA2: thromboxane A2; NO: nitric oxide; EPC: endothelial progenitor cell; ET-1: endothelin-1; PGI2: prostaglandin I2; sGC: soluble guanylate cyclase; cGMP: cyclic guanosine monophosphate; 5-HT: 5-hydroxytryptamine; VEGF: vascular endothelial growth factor; bFGF: basic fibroblast growth factor; TGF-α: transforming growth factor-α; PDGF: platelet-derived growth factor; HGF: hepatocyte growth factor; PPARγ: peroxisome proliferator-activated receptor-γ; STAT3: signal transducer and activator of transcription 3; NFAT: nuclear factor of activated T-cells; MCP-1: monocyte chemoattractant protein-1; TNF: tumour necrosis factor; IL: interleukin; FKN: fractalkine; CCL: chemokine ligand; cAMP: cyclic adenosine monophosphate. Reproduced from [6] with permission from the publisher.
Tables
- Table 1. Pathological changes and disease mechanisms in pulmonary hypertension (PH) subtypes
PH subtype Pathological changes Contributory mechanisms PAH Pathological lesions in distal pulmonary arteries
Medial hypertrophy
Intimal proliferative and fibrotic changes
Adventitial thickening with perivascular inflammatory infiltrates and thrombotic lesionsEndothelial dysfunction, leading to changes in vasoactive and growth regulatory factors
Vascular cell proliferation
Inflammation
ThrombosisPH-LHD Enlarged and thickened pulmonary veins
Pulmonary capillary dilatation
Interstitial oedema
Alveolar haemorrhage
Lymphatic vessel and lymph node enlargement
Medial hypertrophy and intimal fibrosis of distal pulmonary arteriesVasoconstrictive reflexes arising from stretch receptors localised in the left atrium and pulmonary veins
Endothelial dysfunction
Vasoconstriction
Proliferative remodelling of the pulmonary vessel wallPH-ILD Medial hypertrophy
Intimal obstructive proliferation of the distal pulmonary arteries
Destruction of vascular bed in areas subject to emphysema or fibrosisHypoxic vasoconstriction
Endothelial dysfunction leading to imbalance in vasoactive signalling molecules
Mechanical stress of hyperinflated lungs
Capillary loss
Inflammation
Toxic effects of cigarette smokeCTEPH Persistent organised thrombi in the medial layer of the pulmonary vasculature
Vessel occlusion
Remodelling of the major pulmonary vasculature
Small-vessel pulmonary arteriopathy (indistinguishable from changes seen in PAH)Non-resolution of emboli
Endothelial dysfunction from shear stress, pressure and inflammation
Cytokine release
In situ thrombosis
Vasculotrophic mediator releasePAH: pulmonary arterial hypertension; LHD: left heart disease; ILD: interstitial lung disease; CTEPH: chronic thromboembolic PH. Modified from [1].
