|
| Mechanisms similar to IPAH patients | |
|
| (i) Overactivation of transcription factors (hypoxia inducible factor-1 alpha and Nuclear Factor of activated T lymphocytes) | |
| (ii) Decreased expression of certain voltage gated potassium channels | |
| (iii) De novo expression of the antiapoptotic proteins | |
|
| Mechanisms involving inflammation and autoimmunity | |
|
| (i) Chronic inflammation caused by viral infections and autoimmune diseases, leading to the migration of monocytes, neutrophils, mast cells, and dendritic cells to the structurally damaged pulmonary artery | |
| (ii) Invasion of the elastic lamina, stimulating the release of chemokines, cytokines and growth factors | |
| (iii) Resultant vascular remodeling, collagen deposition, and uninhibited proliferation of endothelial cell | |
|
| Immune dysregulation mechanism | |
|
| (i) Decreased percentage of CD4+/CD25+ T cells, diminished regulation by regulatory T cells and B cells, and stimulated signals to B cells | |
|
| Pathology involving autoantibodies | |
|
| Antiendothelial cell antibodies (AECA) | |
| (i) AECA prevalence ranges from 15% to 80% | |
| (ii) AECA levels are increased in active SLE, in particular in patients with nephritis, PH and vascular injuries. | |
| (iii) AECA enhances release of endothelin-1 | |
| (iv) Binding of AECA or immune complexes may augment release of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) | |
| Antiphospholipid antibodies (aPL) | |
| (i) Present in 40% of patients with SLE | |
| (ii) aPLs activate the endothelial cells, monocytes, and platelets leading to a prothrombotic state | |
| Other autoantibodies in SLE-associated PAH | |
| (i) Antinuclear antibody (ANA) invariably present | |
| (ii) >25% prevalence of ribonuclear protein (RNP) | |
| (iii) 50% to 80% prevalence of rheumatoid factor (RF) | |
|
