Vitamin k2 improves endothelial progenitor cells vascular repair in rats dyslipidaemia

Anne Hazem Elgeziry; Cherine Adel Ismail; Omneya Amin Nayel; Mervat Kamel Barakat; Rasha Ghazala; Amany Abdelbary

Anne Hazem Elgeziry Alexandria faculty of medicine
Cherine Adel Ismail Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
Omneya Amin Nayel Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
Mervat Kamel Barakat Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
Rasha Ghazala Department of medical biochemistry, Faculty of Medicine, Alexandria University, Alexandria, Egypt
Amany Abdelbary Department of pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Keywords: endothelial dysfunction, atherogenesis, CD133, VEGFR-2, NOX4

Abstract

Abstract. Background: Vitamin k₂ (menaquinone-7) was reported to possess a vascular protective action against atherogenesis through reduction of vascular calcification. Objectives: The present study investigated whether the augmentation of endothelial progenitor cells’ (EPCs) reparative capacity could be an underlying mechanism behind vitamin k₂ vasoprotective action, in a rat model of dyslipidaemia. Methods: Forty-five Wistar rats were randomly assigned to normal control (15-rat) or dyslipidaemic rats (30-rat) fed on laboratory show or high fat diet (HFD), respectively. Dyslipidaemic rats were further assigned to receive either vehicle or vitamin k₂ (30 mg/kg) 5 days a week, orally for 8 weeks. At the end of the study, lipid profile was assessed. Thoracic aortae were dissected for histopathological examination, immunostaining for detection of EPCs markers; CD133 and vascular endothelial growth factor receptor-2 (VEGFR-2), and b-catenin expression, and for expression of NADPH oxidase4 (NOX4). Vascular function was assessed biologically in-vitro. Results: Vitamin k₂supplementation conferred an endothelial protection and anti-atherogenic potential when compared to vehicle treated HFD fed rats. The increase in EPCs numbers appears to play a pivotal role in the vaso-protective action of vitamin K₂ that could be mediated by interplay between vascular Wnt/b-catenin signalling and NOX4 expression. Conclusion: 8-week treatment with vitamin k2 increases EPCs count in rats with dyslipidemia and whether continued vitamin k₂supplementation confers sustained EPCs endothelial regeneration warrants further investigation.