|
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) | |
|