Thrombolysis exacerbates cerebrovascular injury after ischemic stroke via a VEGF-B dependent effect on adipose lipolysis
Nilsson, I.; Su, E. J.; Fredriksson, L.; Heller Sahlgren, B.; Bagoly, Z.; Moessinger, C.; Stefanitsch, C.; Ning, F. C.; Zeitelhofer, M.; Muhl, L.; Lawrence, A.-L. E.; Scotney, P. D.; Lu, L.; Samen, E.; Ho, H.; Keep, R. F.; Medcalf, R. L.; Lawrence, D. A.; Eriksson, U.
Show abstract
Cerebrovascular injuries leading to edema and hemorrhage after ischemic stroke are common. The mechanisms underlying these events and how they are connected to known risk factors for poor outcome, like obesity and diabetes, is relatively unknown. Herein we demonstrate that increased adipose tissue lipolysis is a dominating risk factor for the development of a compromised cerebrovasculature in ischemic stroke. Reducing adipose lipolysis by VEGF-B antagonism improved vascular integrity by reducing ectopic cerebrovascular lipid deposition. Thrombolytic therapy in ischemic stroke using tissue plasminogen activator (tPA) leads to increased risk of hemorrhagic complications, substantially limiting the use of thrombolytic therapy. We provide evidence that thrombolysis with tPA promotes adipose tissue lipolysis, leading to a rise in plasma fatty acids and lipid accumulation in the ischemic cerebrovasculature after stroke. VEGF-B blockade improved the efficacy and safety of thrombolysis suggesting the potential use of anti-VEGF-B therapy to extend the therapeutic window for stroke management.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Loss of embryonically-derived Kupffer cells during hypercholesterolemia accelerates atherosclerosis development 95%
- TWIST1 drives endothelial-to-mesenchymal-transition to stabilize atherosclerotic plaques 94%
- Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling 94%
Similar papers in this journal
- ciRS-7 and miR7 regulate ischemia induced neuronal death via glutamatergic signaling 94%
- The paracaspase MALT1 controls cholesterol homeostasis in glioblastoma stem-like cells through lysosome proteome shaping 93%
- MDA-LDL vaccination induces athero-protective germinal center-derived antibody responses 93%
Similar papers in this journal
Similar papers in this journal
- Microglia are not required for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism 94%
- Microglia regulate neuronal activity via structural remodeling of astrocytes 94%
- Spatiotemporal transcriptomic maps of mouse intracerebral hemorrhage at single-cell resolution 93%
Similar papers in this journal
- The myeloid cell-driven transdifferentiation of endothelial cells into pericytes promotes the restoration of BBB function and brain self-repair after stroke 95%
- Dual-modal metabolic analysis reveals hypothermia-reversible uncoupling of oxidative phosphorylation in neonatal brain hypoxia-ischemia 93%
- Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.