Biological complexity: blood vessel controls (Introduction)

by David Turell , Friday, November 11, 2016, 01:29 (2935 days ago) @ David Turell

Every function in life is tightly controlled. This one relates to blood flow, blood pressure and the fact that the pipes are elastic and constantly pulsate:

https://www.sciencedaily.com/releases/2016/11/161110123943.htm

"Physical forces like blood pressure and the shear stress of flowing blood are important parameters for the tension of blood vessels. Scientists have been looking for a measurement sensor for many years that enables the translation of mechanical stimuli into a molecular response, which then regulates the tension in blood vessels.

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"Unlike water pipes, which are often used as a model for explaining the functioning of blood vessels, the latter are anything but rigid and lifeless. Instead, they consist of an elastic vessel wall comprising different layers of highly sensitive tissue. This tissue is able to respond to the changing requirements of the body by increasing the vessel diameter and intensifying the blood flow as a result.

"The blood vessel receives the information necessary for this process from the blood stream itself: "One of the most important control mechanisms is the physical forces exerted by the blood on the interior of the blood vessels," says Stefan Offermanns. "The blood vessel interior is lined with endothelial cells. These register the intensity of the blood flow using molecular antennae." In response to this stimulus, the endothelial cells release nitric oxide, among other things. This causes the vessel musculature to relax and the blood vessel expands.

"In addition to the level of the blood pressure, the mechanical shear forces are the main factor that affects the endothelium via the bloodstream and are crucial for the regulation of blood flow. "Previously, we knew very little about how endothelial cells register the mechanical forces of the flowing blood at molecular level. With PIEZO1, we have now discovered a cation channel that forms the interface that transposes the physical stimulus into a molecular reaction. This, in turn, controls the tension of the blood vessel wall," explains Shengpeng Wang, first author of the study.

"The Max Planck researchers initially observed in cultivated endothelial cells that PIEZO1 triggers a signalling cascade when it is exposed to shear stress: "PIEZO1 is activated by the mechanical stimulus. It causes calcium cations to flow through the channel into the endothelial cells and thereby trigger a chain reaction," says Wang. This signalling cascade culminates in the release of nitric oxide and the expansion of the blood vessel. (my bold)

"The Max Planck researchers were able to confirm what they had observed in the laboratory in the living organism using genetically modified mice. Mice with an inactive PIEZO1 gene had higher blood pressure than the control animals. "Due to the lack of the PIEZO1 molecular sensor, the shear forces were not correctly perceived by the endothelial cells and the entire signalling cascade was scarcely activated at all," explains Wang. The cells then released less nitric oxide and the blood vessel musculature remained tense. This, in turn, caused permanently raised blood pressure in the animals.

"If PIEZO1 proves to be the long-sought sensor with which the endothelial cells register the mechanical forces of the flowing blood column so as to regulate the tension of blood vessels, it could be of therapeutic importance."

Comment: The bolded area discusses a cascade, which means in biochemistry that a series of protein molecules trigger each next molecule in the cascade to react and produce the proper control levels with the final products. In blood clotting close to 20 molecules are in the cascade. Since reactions of this sort are stepwise, one should wonder how they develop in evolution by chance. This must be an all-at-once saltation.