Biologists have discovered extracellular signal source of the high blood pressure

Thrombospondin protein-1 (Thbs1), which is contained in the extracellular matrix, transmits the cells of the blood vessel wall mechanical stress, reported in the Proceedings of the National Academy of Sciences. This helps the blood vessels react to high blood pressure. Animals without functional Thbs1 worse tolerate experimental hypertension. Probably, manipulation of this protein will allow to find a new approach to the treatment of diseases of the cardiovascular system.

The walls of the blood vessels are elastic: they contain smooth muscle cells that can stretch and shrink depending on how intense the flow of blood through them. To correctly respond to a change in its intensity, the smooth muscle needs to receive signals from the environment. Their immediate environment is the extracellular matrix (ECM) is a mixture of proteins that the different cells secrete outwards. Some of the proteins of ECM transmits the signals of blood pressure the cells of smooth muscles, was not previously known.

Staff Zukovskogo University headed Yanagisawa Hiromi (Hiromi Yanagisawa) were subjected to culture smooth muscle cells that were isolated from the aorta of adult male rats, the periodic stretching and compression of 20 percent of the volume. This corresponds to pathologically high blood pressure. The whole cycle took one second, the exposure lasted 20 hours. The composition of the extracellular matrix was determined using quantitative mass spectrometry.

In nutrient medium to several cultures added of brefeldin A — inhibitor of protein transport from the endoplasmic reticulum to the Golgi apparatus. As the components of the VCR are highlighted in smooth muscle, it is eventually blocked the exit of proteins to the extracellular matrix outside (out of the cells to different substances help the bubbles, which are produced by the Golgi apparatus). By what unusual proteins remains in this case in the cells, it was possible to determine which of these molecules is responsible for the perception of mechanical stress.

Periodic tension and compression increased production of several proteins, one of which was thrombospondin-1 (Thbs1). In a series of experiments when protein transport was blocked immediately, but after several hours of cyclic stretching and compression, the scientists determined that thrombospondin-1 controls actin filaments in the cellular composition of the skeleton and changes in orientation of smooth muscle cells in response to changes in pressure of blood on them.

Since it is known that on the surfaces of cells of various types there are many receptors for Thbs1, the researchers tried to block them and found that in the case of smooth muscle in the part of the aorta thrombospondin-1 joins integrins αv and β1.

Next, the action of thrombospondin-1 it was necessary to establish in practice. To do this, biologists have done laboratory mice with the normal gene of this protein, and animals with nokauti gene thbs1 (they trombospondin not supposed to work) surgery, in which blood from the heart had to go through a significantly narrowed aorta. Five weeks after surgery, all mice wild-type (that is, without genetic changes) were alive and in the group without morphological and functional of thrombospondin-1 31.9 per cent of the rodents (7 of 22) were killed. Three of them at autopsy found a rupture of the aorta. Thbs1 did the walls of the vessel more tight, due to which they can withstand the powerful pressure of blood flow, and the knockout of the corresponding gene, the protective effect of thrombospondin-1 was not observed.

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