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Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall

  • Ortega, Miguel A1, 2, 3
  • Fraile-Martínez, Oscar1
  • García-Montero, Cielo1
  • Ruiz-Grande, Fernando4, 1
  • Barrena, Silve4
  • Montoya, Hector1
  • Pekarek, Leonel1
  • Zoullas, Sofia1
  • Alvarez-Mon, Miguel A1
  • Sainz, Felipe1, 5
  • Asúnsolo, Angel2, 1
  • Acero, Julio2, 1
  • Álvarez-Mon, Melchor1, 2, 6
  • Buján, Julia1, 2
  • García-Honduvilla, Natalio1, 2
  • Guijarro, Luis G2, 7
  • 1 , Madrid, Spain
  • 2 Ramón y Cajal Institute of Healthcare Research (IRYCIS), Madrid, Spain
  • 3 Cancer Registry and Pathology Department, Hospital Universitario Principe de Asturias, Alcalá de Henares, Madrid, Spain
  • 4 Angiology and Vascular Surgery Service, Hospital Universitario Principe de Asturias, Alcalá de Henares, Madrid, Spain
  • 5 Angiology and Vascular Surgery Service, Central University Hospital of Defence-UAH Madrid, Spain
  • 6 Immune System Diseases-Rheumatology, Oncology Service and Internal Medicine (CIBEREHD), University Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
  • 7 Unit of Biochemistry and Molecular Biology (CIBEREHD), Department of System Biology, University of Alcalá, Alcalá de Henares, Spain
Published Article
The Journal of International Medical Research
SAGE Publications
Publication Date
Sep 30, 2021
DOI: 10.1177/03000605211041275
PMID: 34590920
PMCID: PMC8489764
PubMed Central
  • Pre-Clinical Research Report


Objectives Chronic venous disease (CVeD) is a multifactorial and debilitating condition that has a high prevalence in Western countries and an important associated socioeconomic burden. Varicose veins (VVs) are the most common manifestations of CVeD. Pathologically, many morphological and functional changes have been described in VVs, which most notably affect venous wall integrity. Previous studies have found several molecular alterations that negatively affect normal cell signaling pathways. Insulin receptor substrate (IRS)-4 is a central adaptor protein that is closely related to insulin/insulin-like growth factor-1 signaling upstream, phosphatidylinositol 3-kinase/Akt or mitogen-activated protein kinases downstream, and other proteins. These molecular pathways have been implicated in CVeD pathogenesis. Thus, the aim of our study was to identify the role of IRS-4 in VV tissue. Methods We conducted a histopathological study to analyze IRS-4 protein expression in CVeD patients compared with healthy controls. Results Our results demonstrate a significant increase in IRS-4 expression in VV tissue. Conclusions IRS-4 may be implicated in CVeD development and progression. Therefore, IRS-4 could be a potential diagnostic or therapeutic target for patients with this condition.

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