Morphological Reconstruction of Main Arteries by Perivascular Implantation of Sulfated Chitosan in Experimental Atherosclerosis

Abstract

The aim of the study is to demonstrate morphological reconstruction of the main arteries of rabbit hind limbs by perivascular implantation of sulfated chitosan in an atherosclerosis model.Materials and Methods. The study was performed on 24 rabbits divided into four groups of 6 animals. The rabbits in the experimental group kept on intensive cholesterol diet for 110 days were implanted 1% water-soluble sulfated chitosan gel in the perivascular fascial compartment of the saphenous artery and the femoral artery of the left hind limb. Some animals that were also kept on cholesterol diet did not undergo implantation. The group of rabbits fed with normal vivarium diet were subjected to perivascular implantation of the biopolymer, while a group of 6 rabbits also kept on normal diet served as the intact control. We estimated wall thickness of the femoral artery and the saphenous artery, their average lumen diameter, the mean lumen area of the newly formed vessels in the adventitia.Results. Daily intensive cholesterol diet for 3.5 months in rabbits leads to vivid signs of atherogenic inflammation forming in the intimal and medial layers of the main arteries of the hind limbs. Introduction of 1% water-soluble sulfated chitosan gel into the paravasal compartment of the saphenous and femoral arteries promotes formation of a large number of microvessels at the polymer resorption site increasing the specific area of new vessels. Morphological reconstruction of the main arteries is achieved through reducing the vascular wall thickness, increasing the vessel lumen and the number of para-adventitial microvessels.Conclusion. Implantation of sulfated chitosan into the perivascular compartment allows achieving the effect of therapeutic paravasal angiogenesis and inhibiting the early signs of atherogenic inflammation.Key words: atherogenic inflammation; perivascular implantation of chitosan; ischemia of the hind limbs; therapeutic angiogenesis; morphological reconstruction of the vessel wall; biodegradable polymer.

Synthesis, Chemical and Biomedical Aspects of the Use of Sulfated Chitosan

“…The dislocation of sulfated chitosan near cell membranes in the subintimal region suggests its active interaction with cholesterol in macrophages, its binding to extracellular and intracellular cholesterol, and transport of its water-soluble electrolyte complex with lipid mass [61] into the para-adventitial region in the composition of chitosan nuclei [60]. It is assumed that the targeted transport of lipid fractions occurs due to an electrostatic gradient [64][65][66], which is caused by artificial minimally invasive dislocation of chitosan [47] in the fascial sheath of large vessels. Our study convincingly shows the local release of cholesterol and low-density lipoproteins from the arterial wall.…”

“…This flow outside the outer shell of the vessel can be provided by an electrostatic gradient, which is created due to the polycationic properties of chitosan [60,64]. Artificial minimally invasive dislocation of chitosan nanoparticles in the fascial sheath of the main vessels provides this gradient [65,66] and can be designed for the directed flow of the lipid mass towards the adventitia.…”

Marine Natural Products and Coronary Artery Disease

“…Chitoheptaose was also proven in an experiment to obtain oxidant, inflammatory, and apoptotic resistance so that it could defend the heart in a model of myocarditis ( 58 ). Recent studies indicated that if chitosan sulfate was embedded into the perivascular chamber, remedial angiogenesis could be achieved to restrain the initial indication of atherosclerotic inflammation ( 59 ).…”

Current Research Landscape of Marine-Derived Anti-Atherosclerotic Substances

“…Li et al conjugated hydroxybutyl chitosan (HBC) to anti-CD133 antibody to prepare a CD133 antibody-coated stent, which has shown the ability to decrease intimal hyperplasia and reduce restenosis in contrast with bare stents, which suggests that the stents of the CD133 antibody coat may contribute to the treatment of AS [116]. In addition, implantation of sulfated chitosan into the perivascular compartment achieves therapeutic paravasal angiogenesis and inhibits the early signs of atherogenic inflammation [117]. These studies provide new research directions and treatment ideas for AS and stimulate further development of chitosan and its derivatives in this field.…”