Regeneration of blood vessels

A new study led by researchers identifies a signaling pathway that is essential for angiogenesis, the growth of new blood vessels from pre-existing vessels. The finding may improve current strategies to improve blood flow in ischemic tissue, such as that found in atherosclerosis and peripheral vascular disease associated with diabetes.

The research shows that the formation of fully functional blood vessels requires activation of protein kinase Akt by a protein called R-Ras, and this mechanism is necessary for the formation of the hallow structure, or lumen, of a blood vessel.This showed the biological process needed to increase blood flow in ischemic tissues.

Research team used a combination of 3D cell culture and living tissue to show that vascular endothelial growth factor VEGF promotes vascularization, but the vessel structures formed are chaotic, unstable and non-functional. Functional vessels need to have a lumen; a pipe-like opening that allows oxygenated blood and nutrients to travel through the body and VEGF alone cannot fully support the formation of such a vessel structure.

 VEGF activates Akt to induce endothelial cells to sprout. Then, R-Ras activates Akt to induce lumen formation. The second step involving Akt activation by R-Ras stabilizes the microtubule cytoskeleton in endothelial cells, creating a steady architecture that promotes lumen formation. VEGF and R-Ras activation of Akt signaling are complementary to each other, both are necessary to generate fully functional blood vessels to repair ischemic tissue.  
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Nanoparticles can limit inflammation

An injection of nanoparticles may boost the immune system when it becomes weak. Inflammation is a double-edged sword. When it works, it helps the body heal and fights off infections. But sometimes, the immune system overreacts. An acute lung injury, sustained by inhaling smoke, for instance, can lead to runaway fluid production that essentially drowns a person.

Experiments in mice suggest that simple plastic nanoparticles, delivered by IV, may be able to keep a type of immune cell called a neutrophil too busy to cause inflammation. Other diseases in which neutrophils cause excessive inflammation include sepsis and the hardening of the arteries, or atherosclerosis.

Researchers designed an experiment injuring part of the blood vessel wall in the microfluidic chips and confirmed that the neutrophils were redirecting their attention from creating inflammation at the injury site to carting the foreign particles away. In mice with acute lung injury, they found that injecting nanoparticles by IV could reduce the number of neutrophils congregating at the injury site by half or more.

The neutrophil concentration was similar to the concentration found in the blood of uninjured mice. Instead, the neutrophils were taking the particles to the liver, where they could be removed from circulation. The chemicals that the team uses to attach the nanoparticles to the blood vessel walls are the same as those used by the neutrophils themselves, a coating that combines nonfouling materials with the targeting chemicals will throw most white blood cells off.
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