Chymotrypsin-like proteinases

Chymotrypsin-like proteinases in human blood plasma are normally absent and can enter it from granulocytes or damaged tissues, for example, with hereditary hypercholesterolemia, nonspecific aortoarteritis.

Stress induces changes associated with an increase in the content of neuropeptides, a decrease in the activity of neuropeptide-regulating enzymes and, in particular, mast cell chymase.

Inactivation of chymase can occur under the action of inhibitors (a-1-inhibitor of proteinase and a-1-antichymotrypsin), localized in mast cells.

Methods for detecting chymase are based on the addition of specific mast cell activators, for example, anti-IgE, g-globulin, and inhibition by chymostatin.

Human chymase is also involved in the extracellular formation of AII, which leads to an increase in intracardiac AII formation, especially in a hypertrophied heart and entails a narrowing of the coronary vessels, a decrease in diastolic relaxation, and an increase in the number of myocytes and fibrous connective tissue. The presence of the chymotrypsin-like proteinase chymase in the mast cells of the heart is due to the so-called alternative pathway of AII formation. To date, biochemical studies have proven chymase-dependent formation of AII, but the participation of this enzyme in the physiological and pathological regulation of blood pressure and heart activity remains incompletely clarified. It was shown, in particular, that in patients with significant lesions of the myocardium, ACE of the heart, and not chymase,makes a more significant contribution to the activation of ASD.

The elements necessary for the formation of AII by chymase are localized in the tissues of the heart, vessels, and lungs. kidneys, adrenal glands, brain. The heterogeneity and wide distribution of chymase in human tissues indicates its significant role in the regulation of physiological functions in various tissues.

To date, not only chemically in a chemically pure form, but also its DNA and mRNA has been isolated. To identify chymase, polymorphic marker A (-1903) G of the heart chymase gene (CMA1) is used. Polymorphism A (-1903) G is due to the nucleotide substitution of A for G in the position -1903 of the 5′-untranslated region of the CMA1 gene.

Immunocytochemically using antibodies to chymase, its presence in the endothelium and interstitial myocardial cells, granules of mast cells and some mesenchymal cells was established.

The presence of various pathways for the formation of angiotensin II can be important with long-term therapy with ACE inhibitors due to the fact that prolonged use of the latter not only reduces the amount of circulating angiotensin II, but also increases the concentration of angiotensin I by a factor of 2-3. may activate the chymazo-dependent pathway of angiotensin II formation.

In the works on the angiotensin II type 1 receptor gene, 4 main types of angiotensin II receptors are described . The most interesting are type 1 angiotensin receptors located on the vascular endothelium and mediating all the major cardiovascular effects of angiotensin.

local_offerevent_note August 10, 2019

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