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Tissue remodelling and increased DNA damage in patients with incompetent valves in chronic venous insufficiency |
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| Authors: | Miguel A Ortega Oscar Fraile-Martínez Cielo García-Montero Leonel Pekarek Miguel A Alvarez-Mon Luis G Guijarro Maria del Carmen Boyano Felipe Sainz Melchor Álvarez-Mon Julia Buján Natalio García-Honduvilla Ángel Asúnsolo |
| Institution: | 1. Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Spain;2. Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Spain
Contribution: Investigation (equal);3. Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Spain Ramón y Cajal Institute of Healthcare Research (IRYCIS), Madrid, Spain;4. Ramón y Cajal Institute of Healthcare Research (IRYCIS), Madrid, Spain Unit of Biochemistry and Molecular Biology, Department of System Biology, University of Alcala, Alcalá de Henares, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain Contribution: Investigation (equal);5. Unit of Biochemistry and Molecular Biology, Department of System Biology, University of Alcala, Alcalá de Henares, Spain;6. Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Spain Angiology and Vascular Surgery Service, Central University Hospital of Defence-UAH Madrid, Alcalá de Henares, Spain Contribution: Investigation (equal);7. Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Spain Ramón y Cajal Institute of Healthcare Research (IRYCIS), Madrid, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain Immune System Diseases-Rheumatology, Oncology Service and Internal Medicine, University Hospital Príncipe de Asturias, Alcalá de Henares, Spain Contribution: Conceptualization (equal), Funding acquisition (equal), Investigation (equal);8. Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Spain Ramón y Cajal Institute of Healthcare Research (IRYCIS), Madrid, Spain Contribution: Investigation (equal);9. Ramón y Cajal Institute of Healthcare Research (IRYCIS), Madrid, Spain Unit of Biochemistry and Molecular Biology, Department of System Biology, University of Alcala, Alcalá de Henares, Spain Department of Epidemiology and Biostatistics, Graduate School of Public Health and Health Policy, The City University of New York, New York, NY, USA Contribution: Investigation (equal) |
| Abstract: | Chronic venous insufficiency (CVI), in which blood return to the heart is impaired, is a prevalent condition worldwide. Valve incompetence is a complication of CVI that results in blood reflux, thereby aggravating venous hypertension. While CVI has a complex course and is known to produce alterations in the vein wall, the underlying pathological mechanisms remain unclear. This study examined the presence of DNA damage, pro-inflammatory cytokines and extracellular matrix remodelling in CVI-related valve incompetence. One hundred and ten patients with CVI were reviewed and divided into four groups according to age (<50 and ≥50 years) and a clinical diagnosis of venous reflux indicating venous system valve incompetence (R) (n = 81) or no reflux (NR) (n = 29). In vein specimens (greater saphenous vein) from each group, PARP, IL-17, COL-I, COL-III, MMP-2 and TIMP-2 expression levels were determined by RT-qPCR and immunohistochemistry. The younger patients with valve incompetence showed significantly higher PARP, IL-17, COL-I, COL-III, MMP-2 and reduced TIMP-2 expression levels and a higher COL-I/III ratio. Young CVI patients with venous reflux suffer chronic DNA damage, with consequences at both the local tissue and systemic levels, possibly associated with ageing. |
| Keywords: | cellular damage matrix remodelling PARP valve incompetence |