1. Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, 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. Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain.
5. UFR of pharmacy, University of Clermont Auvergne, Clermont-Ferrand, France.
6. Pathological Anatomy Service, Central University Hospital of Defence-UAH Madrid, Spain.
7. Angiology and Vascular Surgery Service, Central University Hospital of Defence-UAH Madrid, Spain.
8. Immune System Diseases-Rheumatology, Oncology Service and Internal Medicine, University Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain.
*These authors contributed equally in this work.
#These authors shared senior authorship in this work.
Chronic venous insufficiency (CVI) is one of the most common vascular pathologies worldwide. One of the risk factors for the development of CVI is aging, which is why it is related to senile changes. The main trigger of the changes that occur in the venous walls in CVI is blood flow reflux, which produces increased hydrostatic pressure, leading to valve incompetence. The cellular response is one of the fundamental processes in vascular diseases, causing the activation of cell signalling pathways such as c-Jun N-terminal kinase (JNK). Metabolic changes and calcifications occur in vascular pathology as a result of pathophysiological processes. The aim of this study was to determine the expression of JNK in venous disease and its relationship with the role played by the molecules involved in the osteogenic processes in venous tissue calcification. This was a cross-sectional study that analyzed the greater saphenous vein wall in 110 patients with (R) and without venous reflux (NR), classified according to age. Histopathological techniques were used and protein expression was analysed using immunohistochemistry techniques for JNK and markers of osteogenesis (RUNX2, osteocalcin (OCN), osteopontin (OPN)). Significantly increased JNK, RUNX2, OCN, OPN and pigment epithelium-derived factor (PEDF) protein expression and the presence of osseous metaplasia and amorphous calcification were observed in younger patients (<50 years) with venous reflux. This study shows for the first time the existence of an osteogenesis process related to the expression of JNK in the venous wall.
Keywords: chronic venous insufficiency, venous reflux, JNK, osteogenesis, ageing