Hypercholesterolemia-induced increase in plasma oxidized LDL abrogated pro angiogenic response in kidney grafts

• DOI: 10.1186/s12967-018-1764-4
• Publication Date: 2019-01-14T09:04:46Z
• Authors: Thomas Kerforne; Frédéric Favreau; Tackwa Khalifeh; Souleymane Maiga; Geraldine Allain; Antoine Thierry; Manuel Dierick; Edouard Baulier; Clara Steichen; Thierry Hauet
• Keywords: Thrombospondin 1; Endothelial Dysfunction; Dyslipidemia

Renal transplantation is increasingly associated with the presence of comorbidity factors such as dyslipidemia which could influence graft outcome. We hypothesized that hypercholesterolemia affect vascular repair processes and promote post-transplant renal remodeling through over-expression anti-angiogenic thrombospondin-1 interacting endothelial growth factor-A levels. tested this hypothesis in vitro, vivo a human cohort using (1) cells; (2) kidney auto-transplanted pig subjected (n = 5) or not 6) to diet enriched cholesterol (3) transplanted patient (16 patients). Cells exposed oxidized LDL showed reduced proliferation an increased expression thrombospondin-1. In pigs, 3 months after grafts, we observed deregulation hypoxia inducible factor 1a—vascular axis induced cholesterol-enriched animals concomitant overexpression decrease cortical microvessel density promoting remodeling. patients, was decreased plasma levels during early follow up chronic dysfunction. These results support potential mechanism high fat-diet impedes suggest value controlling cholesterolemia recipient even at stage transplantation.