Breathing Exercises for Your Heart
http://link.springer.com/article/10.1007/s10456-014-9455-0
Abstract
Angiogenesis, the formation of new
blood vessels from pre-existing vessels, is a complex process that
warrants cell migration, proliferation, tip cell formation, ring
formation, and finally tube formation. Angiogenesis is initiated by a
single leader endothelial cell called “tip cell,” followed by vessel
elongation by “stalk cells.” Tip cells are characterized by their long
filopodial extensions and expression of vascular endothelial growth
factor receptor-2 and endocan. Although nitric oxide (NO) is an
important modulator of angiogenesis, its role in angiogenic sprouting
and specifically in tip cell formation is poorly understood. The present
study tested the role of endothelial nitric oxide synthase (eNOS)/NO/cyclic GMP (cGMP)
signaling in tip cell formation. In primary endothelial cell culture,
about 40 % of the tip cells showed characteristic sub-cellular
localization of eNOS toward the anterior progressive end of the tip cells, and eNOS became phosphorylated at serine 1177. Loss of eNOS
suppressed tip cell formation. Live cell NO imaging demonstrated
approximately 35 % more NO in tip cells compared with stalk cells. Tip
cells showed increased level of cGMP
relative to stalk cells. Further, the dissection of NO downstream
signaling using pharmacological inhibitors and inducers indicates that
NO uses the sGC/cGMP pathway in tip cells to lead angiogenesis. Taken together, the present study confirms that eNOS/NO/cGMP signaling defines the direction of tip cell migration and thereby initiates new blood vessel formation.
I am amazed to finally have some idea of how collateral blood vessels form near a damaged area. Thank God science is speeding up. It took scientists 100 years to find out how aspirin worked (i.e., what it was doing at the cellular level).
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