JAK-2 V617F Mutation in Endothelial Cells of Patients with Atherosclerotic Carotid Disease.

ABSTRACT

Objective: It has been shown that clonal mutations occur in hematopoietic stem cells with advancing age and increase the risk of death due to atherosclerotic vascular diseases, just like in myeloproliferative neoplasms. It is known that endothelial cells (EC) and hematopoietic stem cells develop from a common stem cell called hemangioblast in early embryonic period. However, the presence of hemangioblast in the postnatal period is controversial. In this study, JAK2 gene variants was examined in patients with atherosclerotic carotid disease and without any hematological malignancy. Materials and Methods: Ten consecutive patients (8 men and 2 women) with symptomatic atherosclerotic carotid stenosis were included in this study. EC (CD31+CD45-) were separated from tissue samples taken by carotid endarterectomy. JAK2 variants was examined in EC, peripheral blood mononuclear cells and oral epithelial cells of the patients with next generation sequencing. Results: The median age of the patients was 74 (58-80) and the median BMI was 24,44 (18,42-30,85) kg/m2. Smoking history was present in 50%, hypertension in 80%, diabetes in 70%, and ischemic heart disease in 70% of the patients. JAK2V617F mutation was detected in peripheral blood mononuclear cells in three out of 10 patients, two of them also had JAK2V617F mutation in their EC. JAK2V617F mutation was not found in oral epithelial cells in any of the patients. Conclusion: In this study, for the first time in the literature, we showed that JAK2V617F mutation was found somatically in both peripheral blood cells and EC in patients with atherosclerosis. This finding may support that EC and hematopoietic cells originate from a common clone or that the somatic mutation can be transmitted to EC by other mechanisms. Examining the molecular and functional changes caused by JAK2V617F mutation in EC may help open a new avenue for treating atherosclerosis.