title: Enhanced mRNA expression of plasminogen activator inhibitor-1 in livedoid vasculopathy lesions.
abstract: OBJECTIVE
  Thrombosis and inflammation play an important role in pathophysiology of livedoid vasculopathy (LV). Plasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of fibrinolysis and is a pivotal modulator in a broad range of biological processes.
  
  
  METHODS
  The study specimens were retrospectively selected from archives of pathology department. We investigated PAI-1 mRNA expression in the paraffin blocks of patients with biopsy-proven LV and controls. We analyzed the presence of thrombus, fibrinoid necrosis, ulcer, and epidermal atrophy in study samples. The correlation between histologic findings and PAI-1 expression was investigated.
  
  
  RESULTS
  Analyses were performed in 14 LV patients (mean age 31±20, 79% female) and 4 controls (mean age 64±19, 50% female). PAI-1 gene expression was significantly higher in LV compared to the control group (median 7.74 (Iqr:13.94) vs 1.0 (0.31)), P=.011. Histological analysis displayed that fibrinoid necrosis was present on all patients with LV, 61.5% displayed thrombus, 46.2% displayed ulcer, and 15.4% displayed epidermal atrophy. Overall, we did not observe any discerning difference in PAI-1 expression between the LV blocks with or without thrombus, fibrinoid necrosis, or epidermal atrophy, yet the LV specimens that displayed ulcer histologically had higher PAI-1 mRNA expression compared to those without ulcer (median 13.98 (Iqr:19.21) vs 2.86 (5.59)), (P=.046).
  
  
  CONCLUSIONS
  PAI-1 mRNA expression is significantly increased in cutaneous lesions of patients with LV. Histological finding of ulcer is associated with increased PAI-1 expression in LV specimen. In the current era of PAI-1 inhibitors, enhanced local PAI-1 expression can form a novel and local therapeutic target in LV.
authors.affiliation: Department of Cardiology, Faculty of Medicine, Medeniyet University, Istanbul, Turkey.
authors.forename: Mehmet
authors.identifier: http://orcid.org/0000-0002-4873-4391
authors.initials: M
authors.lastname: Agirbasli
authors.affiliation: Department of Dermatology, Haydarpasa Numune Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Göktay
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Marmara University, Istanbul, Turkey.
authors.forename: Irem
authors.initials: I
authors.lastname: Peker
authors.affiliation: Department of Pathology, Haydarpasa Numune Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.
authors.forename: Pembegul
authors.initials: P
authors.lastname: Gunes
authors.affiliation: Department of Pathology, Haydarpasa Numune Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.
authors.forename: Fugen Vardar
authors.initials: FV
authors.lastname: Aker
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Marmara University, Istanbul, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Akkiprik
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D005260:Female; D005819:Genetic Markers; D006801:Humans; D054068:Livedo Reticularis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012867:Skin / Q000737:chemistry* / Q000473:pathology; D012883:Skin Ulcer / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051321:SERPINE1 protein, human
keywords: Fibrinolysis; Plasminogen activator inhibitor 1; Plasminogen inactivators; Thrombosis; Topical administration; Vascular diseases