Abstract 5882: Hematopoietic Alterations Contribute to the Increased Risk of Thrombosis Observed in Diabetes Type 2 and the Metabolic Syndrome
Introduction Diabetes (DM) and the metabolic syndrome (MetS) have been linked to high atherothrombotic risk. However, intensive glycemic control has shown little effect on macrovascular complications. We hypothesize that a glucose-independent mechanism may be responsible for the observed increased risk.
Objective To analyze the contribution of cells of the hematopoietic compartment to the thrombotic risk observed in DM2 and MetS.
Methods Zucker diabetic fatty (ZD), Zucker fatty (ZF) and control (ZC) rats were subjected to bone marrow (BM) transplants. Cyclophosphamide and busulfan were used to immunosuppress recipients. In wild type and transplanted rats, thrombus formation was photochemically induced in mesenteric vessels and monitored by intravital microscopy. Time needed to produce a full occlusion (OT) was measured. Platelet count (PN) and mean platelet volume (MPV) were also analyzed.
Results Wild-type ZD (A) and ZF (B) rats showed significantly lower OTs (1.0±0.1 & 0,9±0.1min; p<0,0001) than ZC (C; 3,0±0.2min). ZC-BM transplanted to ZC-hosts did not modify OTs compared to those of wild-type ZC (D; 3.9±0.4min). Interestingly, ZC-BM prolonged OTs in ZD- and ZF-hosts (E: 6.7±0.4 & F: 2.4±0.2min; p<0.0001 vs. A&B, respectively). Inversely, ZD-BM reduced OTs in ZC to those of A (G: 0.9±0.1min; p<0.0001 vs. D). This effect was not observed with ZF-BM (H: 3.4±0.2min). Glucose levels were A: 457.8±18.1 B: 85.6±6.7 and C: 92.5±3.5mg/dL and were not changed by transplantation. MPV in ZD & ZF was significantly higher (6.8±0.1 & 7.0±0.1μm3, respectively; p<0.0001) than in ZC (6.4±0.1 μm3) whereas ZC-BM showed no effect (D: 6.3±0.1, E: 7.1±0.10, F: 7.10±0.1μm3). ZD- and ZF-BM increased MPV in ZC (G: 6.7±0.2 & H: 6.7±0.1μm3; p<0.05 vs. D). PN was increased in A & B (615±44 & 718±49×103/mm3; p<0.05 & p<0.0001, respectively) compared to C (507±24×103/mm3). PN was not modified by transplantation.
Conclusions Alterations in the hematopoietic lineage cells, independently from plasma glucose levels, contribute to increased thrombotic risk in DM and MetS. DM and MetS BM-derived cells confer a prothrombotic phenotype regardless of the host. Funded by PNS-SAF2006/10091-MEC, CIBEROBN (CB06/03) and TERCEL, Instituto de Salud Carlos III, Spain.