The relationship of cardiovascular disease with increased intestinal permeability: results from scientific and controlled clinical trials. Focus on the potential of rebamipide


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Abstract

Today, more and more data are emerging indicating the role of disturbances in the structure of the intestinal barrier in patients with cardiovascular diseases. This is due to the fact that in the settings of increase in intestinal permeability, translocation of biologically active substances, bacterial endotoxins, their antigenic determinants and microorganisms themselves from the intestinal lumen make take place. This entails the stimulation of the processes of atherogenesis, low degree inflammation and even directly damage cardio-myocytes due to the expression on them of receptors with which lipopolysaccharides of bacterial origin can bind, leading to damage to the myocardium, reducing its contractility and stimulating pro-inflammatory shift. Intestinal endotoxins are capable to induce oxidative modification of low-density lipoproteins, damage to endothelial cells and even stimulating the recruitment of inflammatory cells, which ultimately can initiate and aggravate atherosclerotic lesions of the vascular bed. Many factors play are important in increasing the permeability of the intestinal wall, however, the pivotal role is given to the disturbance of the structure and expression of tight junction proteins: occludin, claudins, tricellulin and Zonula occludens - they provide the maintenance of the barrier function in the enterocytes intercellular contacts. Currently, the possibilities of drug correction of increasing the intestinal permeability are being actively studied. A new drug capable of restoring the disturbed permeability of the intestinal barrier is rebamipide, which acts throughout the whole gastrointestinal tract, in contrast to gastro- and enteroprotectors, and allows directly restoring the structure of tight contacts. Rebamipide also has a whole range of additional pleutopathic effects, including stimulating mucus secretion, improving mucosal microcirculation, and even positively affecting components of the gut microbiome. In addition, according to the available research data, the effect of rebamipide may go beyond the gastrointestinal tract, in view of the fact that the anti-atherosclerotic and anti-inflammatory activity of the drug has been demonstrated, which consists in a decrease in the amount of pro-inflammatory cytokines and a histologically verified decrease in the number of foci of atherosclerotic lesions of the major arteries. Special attention should be paid to the excellent safety profile of rebamipide therapy - its appointment, even in doses significantly exceeding therapeutic ones, was not accompanied by the development of unwanted drug reactions. Based on this, the given drug can be considered not only as a tool for directly protecting the gastrointestinal tract, but also as a promising drug for complex therapy of cardiac patients.

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About the authors

Olga D. Ostroumova

Russian Medical Academy of Continuous Professional Education; I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: ostroumova.olga@mail.ru
Dr. Sci. (Med.), Professor, Head of the Department of Therapy and Polymorbid Pathology, Russian Medical Academy of Continuous Professional Education; Professor of the Department of Clinical Pharmacology and Propedeutics of Internal Diseases, I.M. Sechenov First Moscow State Medical University Moscow, Russia

A. I Kochetkov

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

E. E Pavleeva

A.I. Yevdokimov Moscow State University of Medicine and Dentistry

Moscow, Russia

O. V Golovina

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

N. A Arablinsky

Pirogov Russian National Research Medical University (Pirogov Medical University)

Moscow, Russia

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