Alpha-1 antitrypsin or α1-antitrypsin (A1AT, α1AT, A1A, or AAT) is a protein belonging to the serpin superfamily. It is encoded in humans by the SERPINA1 gene. A protease inhibitor, it is also known as alpha1–proteinase inhibitor (A1PI) or alpha1-antiproteinase (A1AP) because it inhibits various proteases (not just trypsin). In older biomedical literature it was sometimes called serum trypsin inhibitor (STI, dated terminology), because its capability as a trypsin inhibitor was a salient feature of its early study. As a type of enzyme inhibitor, it protects tissues from enzymes of inflammatory cells, especially neutrophil elastase, and has a reference range in blood of 0.9–2.3 g/L (in the US the reference range is expressed as mg/dL or micromoles), but the concentration can rise manyfold upon acute inflammation.When the blood contains inadequate amounts of A1AT or functionally defective A1AT (such as in alpha-1 antitrypsin deficiency), neutrophil elastase is excessively free to break down elastin, degrading the elasticity of the lungs, which results in respiratory complications, such as chronic obstructive pulmonary disease, in adults. Normally, A1AT leaves its site of origin, the liver, and joins the systemic circulation; defective A1AT can fail to do so, building up in the liver, which results in cirrhosis in either adults or children. In addition to binding to neutrophil elastase released by inflammatory cells, A1AT also binds to elastase localized on the cell surface in which case elastase does not act as an enzyme, but instead acts to signal cells to undergo locomotion.
Cause
Cherry angiomas appear spontaneously in many people in middle age but can also, less commonly, occur in young people. They can also occur in an aggressive eruptive manner in any age. The underlying cause for the development of cherry angiomas is not understood. Cherry angioma may occur through two different mechanisms: angiogenesis (the formation of new blood vessels from pre-existing vessels), and vasculogenesis (the formation of totally new vessels, which usually occurs during embryonic and fetal development).One study published in 2010 found that a regulatory nucleic acid suppresses protein growth factors that cause vascular growth. This regulatory nucleic acid was lower in tissue samples of hemangiomas, and the growth factors were elevated, which suggests that the elevated growth factors may cause hemangiomas. The study found that the level of microRNA 424 is significantly reduced in senile hemangiomas compared to normal skin resulting in increased protein expression of MEK1 and cyclin E1. By inhibiting mir-424 in normal endothelial cells they could observe the same increased protein expression of MEK1 and cyclin E1 which, important for the development of senile hemangioma, induced cell proliferation of the endothelial cells. They also found that targeting MEK1 and cyclin E1 with small interfering RNA decreased the number of endothelial cells. A study published in 2019 identified that somatic mutations in GNAQ and GNA11 genes are present in many cherry angiomas. These specific missense mutations found in hemangiomas are also associated with port-wine stains and uveal melanoma.