Bone Marrow Cell Transplant From Donors With Cardiovascular Risk Factors Increases the Pro-atherosclerotic Phenotype in the Recipients.

Abstract

Improvement of long-term survival after hematopoietic stem cell transplantation has revealed that these patients have an increased appearance of de novo cardiovascular risk factors. Even though in these clinical studies no relation to transplant-related factors has been found, no attention has been paid to the influence of cardiovascular risk factors affecting the bone marrow donors on the cardiovascular risk of the recipients. Thus, the aim of this study was to analyze, using an animal model, whether transplantation of bone marrow from donors with cardiovascular risk factors increases cardiovascular risk in healthy recipients. Results from transplantation experiments have shown that bone marrow from donors with cardiovascular risk factors induced pro-atherogenic modifications in the cholesterol profile of healthy recipients, increasing the low-density lipoprotein cholesterol fraction in comparison to those transplanted with control bone marrow. Moreover, bone marrow from donors with cardiovascular risk factors induced significant alterations in liver pro-inflammatory state and lipid metabolism-related gene expression that could contribute to alter cholesterol homeostasis. Altogether, these results suggest that cardiovascular risk factors in the donor confer a cardiometabolic alteration to their bone marrow cells that is transferred to noncardiovascular disease transplant recipients, affecting their liver function and increasing their cardiovascular risk.