Physical forces like blood pressure and the shear stress of flowing blood are important parameters for the tension of blood vessels. Researchers have been looking for a measurement sensor for many years that links blood flow and the tension in blood vessels. Now, a study from researchers at the Max Planck Institute identifies just such a sensor, PIEZO1, a cation channel in the inner layer of the blood vessel wall. The team state that their findings could one day provide a starting point for the treatment of high blood pressure. The opensource study is published in the Journal of Clinical Investigation.
Previous studies show that the blood vessel interior is lined with endothelial cells which 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 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. However, very little is known about how endothelial cells register the mechanical forces of the flowing blood at molecular level. The current study shows that the cation channel PIEZO1 is required for the regulation of nitric oxide formation, vascular tone, and blood pressure.
The current study utilises mice with an inactive PIEZO1 gene to show that the animals had higher blood pressure than the control animals. The lab explains that 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. Results show that the cells release less nitric oxide and the blood vessel musculature remains tense; this, in turn, causes permanently raised blood pressure in the animals.
The group state that if it were possible to activate PIEZO1 pharmacologically the cells would react to it in exactly the same way as they would to shear stress. They go on to hypothesize, for this reason, active ingredients that stimulate PIEZO1 could offer a promising option for the treatment of different forms of high blood pressure. They conclude that PIEZO1 could also provide the therapeutic starting point in the case of diseases, in which the spasmodic narrowing of the blood vessels plays a role.
The team surmise that their study shows that the PIEZO1 cation channel translates mechanical stimulus into a molecular response to control the diameter of blood vessels. For the future, the researchers state the it will be interesting to analyze the function and structure of PIEZO1 in various forms of arterial hypertension. They go on to add that at the same time, PIEZO1 is also a potential target for preventive or therapeutic interventions aiming at an alteration of vascular tone.
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