Featured
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Letter |
Mechanosensing by β1 integrin induces angiocrine signals for liver growth and survival
In mouse and human liver models, blood vessel perfusion and mechanical stretching release angiocrine signals from endothelial cells that lead to hepatocyte survival and liver growth.
- Linda Lorenz
- , Jennifer Axnick
- & Eckhard Lammert
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Letter |
Integrin-YAP/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow
YAP and TAZ, effectors of the Hippo pathway, sense mechanical forces generated by blood flow and play a role in atherosclerosis pathogenesis.
- Li Wang
- , Jiang-Yun Luo
- & Yu Huang
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Outlook |
Physiology: Beating stroke
New drugs and more focused therapy might cut down on atrial fibrillation and reduce the incidence of stroke.
- Neil Savage
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Research Highlights |
Low-flow blood-vessel pruning
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Letter |
Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities
Exome sequencing identifies mutations in kelch-like 3 and cullin 3 as causes of a syndrome featuring high blood pressure and electrolyte abnormalities.
- Lynn M. Boyden
- , Murim Choi
- & Richard P. Lifton
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Letter |
S-glutathionylation uncouples eNOS and regulates its cellular and vascular function
The enzyme eNOS is crucial for regulating vascular function as it can produce both the vasodilator nitric oxide and the vasoconstrictor superoxide. Here it is shown that a modification associated with oxidant stress, S-glutathionylation, switches the enzyme from forming nitric oxide to forming superoxide. In hypertensive vessels, S-glutathionylation of eNOS is increased and this is associated with impaired endothelium-dependent vasodilation.
- Chun-An Chen
- , Tse-Yao Wang
- & Jay L. Zweier
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Research Highlights |
Stem cells: Platelets get a boost
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Review Article |
Glial and neuronal control of brain blood flow
- David Attwell
- , Alastair M. Buchan
- & Eric A. Newman
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Letter |
A redox switch in angiotensinogen modulates angiotensin release
Angiotensins have a crucial role in blood pressure regulation and are generated by cleavage of a larger protein, angiotensinogen, by the enzyme renin. Structures of angiotensinogen alone and in complex with renin show that a large conformational change is required to expose the renin-cleavage site. The authors also show that this transition is regulated by oxidation and that women with pre-eclampsia have higher levels of the more active, oxidized, form.
- Aiwu Zhou
- , Robin W. Carrell
- & Randy J. Read
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Letter |
A mechanically stabilized receptor–ligand flex-bond important in the vasculature
Here, a new type of behaviour of receptor–ligand bonds has been identified, by using a new method that links receptor and ligand in a single molecule to measure binding and unbinding. The binding of von Willebrand factor to the glycoprotein Ib α subunit on the surface of platelets is important for coagulation. This receptor–ligand bond is now shown to have two distinct states, one seen at low force and a second that has greater force resistance. This has implications for how increased blood flow activates platelet plug formation.
- Jongseong Kim
- , Cheng-Zhong Zhang
- & Timothy A. Springer
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Letter |
Embolus extravasation is an alternative mechanism for cerebral microvascular recanalization
Uninterrupted blood flow through the small vessels of the brain is essential for cerebral function and viability. Small clots that form in the vessels can be — but are not always — removed by haemodynamic forces and the fibrinolytic system. Here, a third mechanism for the removal of emboli is described: the endothelial cells that line the vessel walls send out membrane projections that envelop the emboli and move them into the perivascular parenchyma tissue. In aged mice, this process is markedly delayed.
- Carson K. Lam
- , Taehwan Yoo
- & Jaime Grutzendler
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Letter |
MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis
During embryonic development, blood vessels remodel in response to blood flow. Here, a genetic pathway is described through which this mechanosensory stimulus is integrated with early developmental signals to remodel vessels of the aortic arch in zebrafish. It is found that the flow-induced transcription factor klf2a is required to induce the expression of an endothelial-specific microRNA, activating signalling through the growth factor Vegf.
- Stefania Nicoli
- , Clive Standley
- & Nathan D. Lawson