Effects of synthetic monocyte chemotactic protein-1 fragment 65-76 on neointima formation after carotid artery balloon injury in rats.

The effects of the synthetic monocyte chemotactic protein-1 (MCP-1) peptide fragment 65-76 (peptide X) on the development of neointima after balloon injury to the carotid artery were studied. The agent was given i.m. at a dose of 33 microg/kg once daily for 28 days after balloon injury. Animals given peptide showed significant suppression of neointima growth 4 and 7 days after lesioning, as indicated by morphometric analysis of sections of lesioned arteries. On days 14 and 28, there were no significant differences in neointima formation in rats given and not given peptide. Peptide administration was not accompanied by any changes in C-reactive peptide concentrations, leukocyte counts, or the population composition of peripheral blood lymphocytes. Use of synthetic peptide X as an inhibitor of leukocyte migration during angioplasty may, along with traditional treatments, decrease the risk of restenosis.

[The effect of synthetic fragment 65-76 of monocyte chemiattractant protein-1 (MCP-1) on neointima growth after carotid artery balloon injury in rats].

Influence of synthetic fragment 65-76 of monocyte chemoattractant protein-1 (MCP-1) (peptide X) on development of neointima after balloon injury of carotid artery was investigated. Peptide X was introduced intramuscularly, 33 pg/kg, daily during 28 days after balloon injury. In days 4 and 7 after intervention, in animals receiving peptide X in comparison with control animals a substantial decrease of neointimal growth was observed. On 14 and 28 days there, was no significant difference in neointima development in rats with and without peptide treatment. Injections of peptide X did not after the C-reactive protein concentration, leukocyte number and lymphocyte subpopulations in peripheral blood. Peptide X treatment along with traditional therapy may be effective in preventing restenosis after angioplasty.

[Plasminogen activators and matrix metalloproteinases during arterial remodeling].

To evaluate the role and interaction of plasminogen activators and matrix metalloproteinases (MMPs) in arterial remodeling in vivo we compared effects of recombinant urokinase- (uPA) and tissue-type (tPA) plasminogen activators on vessel morphology, cell proliferation, inflammatory reaction and MMPs expression in arterial wall after experimental balloon angioplasty. We observed that the periadventitial application of uPA to the injured artery in pluronic gel stimulated neointima formation and inward arterial remodeling as well as cell proliferation and inflammatory leukocytes recruitment. In contrast, tPA attenuated neointima growth, contributed to outward arterial remodeling and did not affect significantly leukocytes recruitment in injured arterial wall. Perivascular uPA increased the content and activity of MMPs, while tPA did not induce such changes. In mouse model of vascular remodeling based on partial ligation of the carotid the content of uPA correlated with neointima growth, tPA content correlated with outward arterial remodeling. Our experiments suggest that plasminogen activators represent specific functional target for attenuating unfavorable inward arterial remodeling.

Urokinase induces ROS production in vascular smooth muscle cells.

Urokinase stimulates the production of superoxide radical in cultured aortal smooth muscle cells simultaneously with activation of the expression of NAD(F)H-oxidases nox1, nox4, and phox22. Antioxidant ebselen abolishes the stimulating effect of urokinase on smooth muscle cell proliferation. The data showed that urokinase can potentiate oxidative stress in the arterial wall and can play an important role in the development of adverse arterial remodeling.

[Expression of T-cadherin in the rat carotid artery wall after balloon injury and in different rat organs]. / Ekspressiia T-kadgerina v razlichnykh organakh, a takzhe v stenke sonnykh arterii pri ballonnom povrezhdenii u krys.

T-cadherin is an unusual glycosilphosphatidylinositol (GPI)-anchored member of the cadherin family of cell adhesion proteins. In contrast to classical cadherins, tissue distribution of T-cadherin so far remained unknown. We examined tissue distribution of T-cadherin in rats using Western blotting and immunohistochemical method. Our results show that T-cadherin is expressed in all types of muscles (cardiac, striated, and smooth muscles), in brain neurons, and spinal cord, in the vessel endothelium, at the apical pole of intestinal villar epithelium, in the basal layer of skin, and eosophagal epithelium. Blood-derived and lymphoid cells as well as connective tissue were T-cadherin-negative. The highest level of T-cadherin expression was revealed in the cardiovascular system. Although T-cadherin was detected in smooth muscle cells, its role in the intimal thickening and restenosis is not known. We examined T-cadherin expression within 1-28 days after balloon injury of rat left carotid arteries. T-cadherin expression was valued immunohistochemically with semiquantitative method. In uninjured arteries, T-cadherin was expressed in endothelial (vWF-positive) cells, and smooth muscle (alpha-actin-positive) cells (SMCs). After denudation of arterial wall, T-cadherin was present both in the media and neointima. We revealed dynamics of T-cadherin expression in the media of injured artery: an essential increase being registered at the stage of cell migration and proliferation in the media and neointima (1-7 days), followed by its decrease to the baseline level (10-28 days). The high upregulation of T-cadherin expression in the media and neointima during migration and proliferation of vascular cells after vessel injury enables us to suggest the involvement of T-cadherin in vessel remodeling after balloon catheter injury.