Endothelial dysfunction

Endothelial dysfunction can manifest itself not only by a disorder of its vascular-motor function, but also by disturbances in the hemostatic system. Markers of endothelial dysfunction can be considered an increase in vilbrand factor and thrombomodulin. When studying the level of these markers in patients with arterial hypertension, it was found that patients with the D / D genotype have a significantly higher level than patients with the genotype I / I. For normotensive patients, no such patterns were found.

Recent studies have significantly changed the understanding of the mechanisms of formation of angiotensin II. In particular, the existence of other enzymes other than ACE that catalyze the cleavage of AI to AII, namely cathepsin G, tonin, imostatin-sensitive AII-releasing enzyme, chymase, has been proven. There is evidence that human chymase is the most significant and specific AII-forming enzyme (its share accounts for about 80% of AII-forming activity in the left ventricle, while the share of ACE is only 10%). Moreover, it is known that AII can also directly be formed from angiotensinogen in a reaction catalyzed by toonin, cathepsin G or tissue plasminogen activator.

ACE is located predominantly in the endothelium, whereas ACE-independent formation of angiotensin II occurs mainly in adventitia. Non-ACE-dependent formation of angiotensin II in tissues is carried out under the action of serine proteases. In the human heart, for example, the main protease that catalyzes the conversion of angiotensin I to angiotens in II is chymase .

In search of an AII-forming ACE inhibitor-resistant enzyme in human heart tissue, serine proteinase, chymase, was identified as the main AII-forming enzyme.

Chymase is a specific proteolytic enzyme in mast cells and is classified as neutral proteinase.

Human chymase is synthesized as a zymogen and is transformed into an active form by splitting the residual signal peptide and dipeptide segment, is released due to the activation of mast cells, and is stored in secret granules in an active form.

It was shown that the main factors regulating the activity of chymase within the granules and its release from them are pH and exposure to heparin. Chymase from mast cells is secreted along with proteoglycans.

Mast cell proteoglycans modulate the secretory, proteoglyconase and peptidase activity of chymase. It is assumed that the magnitude of this in vivo modulation depends on the nature of proteoglycans, with which chymase is released from mast cells. Heparin-containing proteoglycans reduce chymase-induced secretory response, and glycosaminoglycans containing chondroitin sulfate have a smaller effect.

It was also shown that chymase is synthesized and stored in the endothelial cells of the mesenchyme and, after secretion, is localized in the myocardium interstitium, and its expression is higher in the ventricles than in the atria. It differs from AII in cellular and regional distribution, the latter is localized mainly in endothelial cells and fibroblasts, and its expression level is higher in the atria than in the ventricles.

local_offerevent_note August 14, 2019

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