Recipients Inherit a Cardiovascular Risk Factor From Bone Marrow Donors: Implications for Screening of Donors?

Abstract

Previous studies have demonstrated that patients develop de novo cardiovascular risk factors after hematopoietic stem cell transplantation (HSCT) (1). The risk of developing metabolic syndrome in HSCT survivors was increased compared with normal subjects (2,3). HSCT survivors were also more likely to develop hyperinsulinemia, impaired glucose tolerance, hypertriglyceridemia, and abdominal obesity than were non-HSCT patients or healthy controls (4). However, it remains unclear whether increased cardiovascular risk factors are directly associated with transplantation-related factors, including total body irradiation, immunosuppression, and graft-versus-host disease. While HSCT-related treatments in recipients have been proposed as causes of increased cardiovascular risk factors in HSCT survivors (1), other studies have shown that there is no clear correlation between HSCT-related treatments and cardiovascular risk factors (2,3).Bejar et al previously examined whether the presence of cardiovascular risk factors in bone marrow donors contributed to increased cardiovascular risks in recipients. They found that bone marrow cells derived from rats with hypercholesterolemia, obesity, and insulin resistance transferred an increased thrombotic risk to healthy recipients (5). The platelets derived from the bone marrow of diabetic fatty rats exhibited a dysregulated endoplasmic reticulum stress protein that promoted thrombosis in recipients (6). Using diabetic fatty rat models in the current study, the authors discovered that bone marrow cells from diabetic rat donors with cardiovascular risk factors induced proatherogenic alterations in the cholesterol profiles of otherwise healthy recipients by increasing low-density lipoprotein (LDL), but not triglyceride, levels, whereas bone marrow cells derived from healthy donors did not (7). These findings suggest that a cardiovascular risk factor can be transferred from donors to recipients of bone marrow transplants and that the risk factor does not result from bone marrow transplantation itself or transplantation-related treatments. These novel findings may be implicated in clinical HSCT for screening healthy donors.Mechanisms underlying the transfer of cardiovascular risk factors from bone marrow donors to recipients remain unclear. Current studies by Bejar et al revealed that proinflammatory cytokines interleukin (IL)-1b and tumor necrosis factor (TNF)a in the liver were increased in recipients of bone marrow cells derived from diabetic rat donors compared with those from healthy control donors. They also demonstrated direct correlations between liver macrophage markers (CD68 and CD163) and the expression of genes (Lpl, Fabp4, and CD36) that are associated with liver lipid homeostasis (7). Kupffer cells are liver-resident macrophages that can produce proinflammatory cytokines, including IL-1b and TNFa, which, in turn, interfere with lipid metabolism (8). Therefore, the authors proposed that bone marrow cells derived from donors with cardiovascular risk factors promoted the recr...