Endothelial Cell-Derived Von Willebrand Factor, But Not Platelet-Derived, Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice.

OBJECTIVE: VWF (von Willebrand factor) is synthesized by endothelial cells and megakaryocytes and is known to contribute to atherosclerosis. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically and functionally different from endothelial cell-derived VWF (EC-VWF). We determined the role of different pools of VWF in the pathophysiology of atherosclerosis. APPROACH AND RESULTS: Using bone marrow transplantation, we generated chimeric Plt-VWF, EC-VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with thrombospondin type I repeats-13 in platelets and plasma on apolipoprotein E-deficient (Apoe-/-) background. Controls were chimeric Apoe-/- mice transplanted with bone marrow from Apoe-/- mice (wild type) and Vwf-/-Apoe-/- mice transplanted with bone marrow from Vwf-/-Apoe-/- mice (VWF-knock out). Susceptibility to atherosclerosis was evaluated in whole aortae and cross-sections of the aortic sinus in female mice fed a high-fat Western diet for 14 weeks. VWF-knock out, Plt-VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with thrombospondin type I repeats-13 exhibited reduced plaque size characterized by smaller necrotic cores, reduced neutrophil and monocytes/macrophages content, decreased MMP9 (matrix metalloproteinase), MMP2, and CX3CL1 (chemokine [C-X3-C motif] ligand 1)-positive area, and abundant interstitial collagen (P<0.05 versus wild-type or EC-VWF mice). Atherosclerotic lesion size and composition were comparable between wild-type or EC-VWF mice. Together these findings suggest that EC-VWF, but not Plt-VWF, promotes atherosclerosis exacerbation. Furthermore, intravital microscopy experiments revealed that EC-VWF, but not Plt-VWF, contributes to platelet and leukocyte adhesion under inflammatory conditions at the arterial shear rate. CONCLUSIONS: EC-VWF, but not Plt-VWF, contributes to VWF-dependent atherosclerosis by promoting platelet adhesion and vascular inflammation. Plt-VWF even in the absence of a disintegrin and metalloprotease with thrombospondin type I repeats-13, both in platelet and plasma, was not sufficient to promote atherosclerosis.

Surgical stabilization of critical abdominal injuries in a mature rural trauma system: A retrospective study.

BACKGROUND: Worse outcomes following injuries are more likely in rural versus urban areas. In 2001, our state established an inclusive trauma system to improve mortality. In 2015, the trauma system had a consultation visit from the American College of Surgeons' Committee on Trauma, who made several recommendations. We hypothesized that continued maturation of this system would lead to more laparotomies prior to transfer to a higher level of care and better outcomes. METHODS: Our trauma registry was queried to identify all patients transferred between January 1, 2010, and December 31, 2020, who underwent laparotomy either before transfer or within 4 hours of arrival. The preconsultation (2010-2015) and postconsultation periods (2016-2020) were compared. Categorical and continuous variables were compared using χ2 and Mann-Whitney U tests, respectively. RESULTS: We included 213 patients; 63 had laparotomy before transfer and 150 within 4 hours after transfer. Age, injury severity scores, systolic blood pressure, and mechanism of injury were not different between periods. Proportions of laparotomy before and after transfer and outcomes (mortality, hospital length of stay, intensive care unit length of stay, ventilator days) were also similar (p = 0.368 for laparotomy, p = 0.840, 0.124, 0.286, 0.822 for outcomes). Compared with the preconsultation period, the proportion of laparotomy performed before transfer for severe injuries (abdominal Abbreviated Injury Scale score >3) significantly increased postconsultation (57.1% vs. 30.6%, p = 0.011). Incidence of damage-control laparotomies (43.9% vs. 23.6%; p = 0.020) and transfusion of plasma and platelets (33.6% vs. 13.2%; p < 0.001, 22.4% vs. 8.5%, p = 0.007, respectively) significantly increased. CONCLUSION: Identification and surgical stabilization of critical patients at the non-Level I facilities prior to transfer, as well as blood product use and damage-control techniques, improved postconsultation, suggesting a shift in the approaches to surgical stabilization and resuscitation efforts in our trauma system. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.