Deep vein thrombosis (DVT) is the most common type of venous thromboembolism. Patients with DVT are at risk of developing potentially life-threatening complications, such as pulmonary embolism, but also long-term complications, including post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension.1 Current treatments for DVT focus on preventing clot expansion with anticoagulants and vasoactive drugs and by increasing venous blood flow through physical methods. However, anticoagulation cannot accelerate the natural thrombus resolution and reciprocally increases the risk of bleeding. Despite initial management of symptomatic acute events, patients remain at high risk for recurrence and predisposed to developing long-term complications. Transition of thromboembolic events to chronic disease is essentially caused by persistent inflammation resulting in delayed thrombus resolution, fibrosis, and vessel wall damage. Conclusions: T EM orchestrate the inflammatory response in venous thrombosis affecting thrombus resolution.

Background: Inflammatory monocytes are drivers of vascular injury and disease. Results: Depletion of lysozyme M-positive monocytes prevents eNOS uncoupling and iNOS-derived nitro-oxidative stress. Conclusion: Monocytes determine eNOS and iNOS function by directly modulating tetrahydrobiopterin bioavailability. Significance: Understanding the impact of inflammation on endothelial function in detail is essential to identify tailored therapeutic strategies.

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Background: Angiotensin II (ATII) causes hypertension and promotes infiltration of inflammatory cells into the vessel wall. Vascular superoxide formation and shear stress mediated inflammatory remodeling of conduit arteries was shown to be myeloid differentiation factor 88 (MyD88) dependent, but the exact mechanism are unknown. Objective: The goal of this study was to determine the mechanism, how MyD88 contributes to the development of ATII-induced vascular dysfunction and arterial hypertension. Methods and Results: MyD88 deficiency profoundly attenuated ATII-induced (1 mg/kg/d for 7 days) blood pressure increase (measured by radio telemetry) and vascular dysfunction (assessed by aortic ring relaxation studies). Additionally vascular superoxide levels as well as mRNA expression levels of VCAM-1, iNOS, Nox2 were decreased in ATII-infused MyD88 -/- mice compared to WT controls. Aortic flow cytometric analysis revealed that ATII-induced infiltration with CD11b + Ly6C high inflammatory monocytes was significantly dampened in MyD88 -/- mice. ATII led to an increased expression of inflammatory monocyte markers in blood and aorta, which was blocked in MyD88 -/- mice, indicating a role of MyD88 for myeloid cell differentiation. Additionally less IFN-gamma + NK cells were detected in the vessel wall of ATII-treated MyD88 -/- mice and aortic lysates showed reduced mRNA levels of several proinflammatory cytokines like IL-12 and IL-1beta. Bone marrow transfer experiments further revealed a protective effect of MyD88 deficiency in inflammatory cells represented by a reduction of vascular dysfunction and inflammation. Conclusion: We provide first evidence that MyD88 expressed by bone marrow-derived cells plays an essential role in ATII-induced vascular dysfunction and arterial hypertension. Our data indicate that MyD88 is important for cytokine production and might be required for ATII-induced differentiation of monocytes into an inflammatory phenotype.