Open Access4G/4G PAI-1 gene variant in a patient with non-healing ulcers
Author(s) -
Heather Peluso,
Julie Caffrey,
Stephen M. Milner
Publication year - 2015
Publication title -
journal of epidemiological research
Language(s) - English
Resource type - Journals
eISSN - 2377-9330
pISSN - 2377-9306
DOI - 10.5430/jer.v2n1p91
Subject(s) - vitronectin , serpin , plasminogen activator , fibrin , fibrinolysis , wound healing , plasminogen activator inhibitor 1 , angiogenesis , cell migration , serine protease , cancer research , tissue plasminogen activator , medicine , immunology , pathology , gene , biology , chemistry , integrin , cell , endocrinology , protease , genetics , biochemistry , enzyme
Plasminogen activator inhibitor is a serine protease inhibitor from the serpin gene family that modulates fibrin clot breakdown.PAI-1 irreversibly inhibits tissue plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) from activatingplasminogen. PAI-1 also inhibits integrin-vitronectin and vitronectin-vitronectin interactions that are essential for cell migration,adhesion, and angiogenesis. We describe a patient, who developed chronic non-healing ulcers after minimal trauma to severalareas of his body. Genetic testing revealed the 4G/4G homozygous genotype for the polymorphism in the promoter regionof the PAI-1 gene. Increased PAI-1 activity prevents the breakdown of the fibrin clot and cell migration to remodel damagedtissue. A combination of poor clot fibrinolysis and cell recruitment to the site of injury may explain our patient’s non-healingulcers following minor traumatic injury. Early treatment with excision and skin grafting may benefit patients presenting withnon-healing ulcers and the homozygous 4G/4G PAI-1 variant. To our knowledge, there have been no reports in the literatureassociating PAI-1 overexpression and chronic non-healing wounds.