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

Abstract

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.

Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE-/- Mice

“…Several studies have shown that macrophage-subset derived inflammatory mediators and growth factors contribute to intimal lesion enlargement [ 13 – 15 ]. CatK deficiency has been shown to affect macrophage foam cell formation [ 5 ], however the effect of catK on macrophage polarization is unknown.…”

Synthetic peptide fragment (65–76) of monocyte chemotactic protein-1 (MCP-1) inhibits MCP-1 binding to heparin and possesses anti-inflammatory activity in stable angina patients after coronary stenting

“…It should be noted that peptide administration effectively suppressed migration of not only monocytes but also granulocytes. In a rat model of post-angioplasty restenosis, peptide-treated animals showed significant delay of neointimal growth, which was manifested as less pronounced neointima thickening and larger area of vessel lumen observed in 1 week after the intervention [25]. The anti-inflammatory action of Ingramon was detectable with i.v.…”

“…It is now established that many chemokines are able to dimerize. MCP-1 in solution forms dimers through interaction of amino acids in the N-terminal domain [25]. MCP-1 mutants with impaired dimerization are not active in vivo, despite their ability to bind and activate their cognate receptors in vitro [31,38,39].…”

“…Thirty-three patients who gave informed consent to participate in the trial received Ingramon intravenously at 35 lg/kg in six injections (before stent implantation, after 6 h, then two injections at 24-h intervals, and two injections at 48-h intervals), in addition to the standard therapy. The dose of Ingramon and the regimen of injections were established earlier in animal models of inflammation and neointimal growth after experimental angioplasty [23,25]. The control group consisted of 34 patients who received the standard therapy.…”

“…The peptide accumulated at the inflamed limb in rats and showed relatively low degradation level in human plasma in vitro, where it was stable for at least 24 h [23,24]. The peptide activity was further tested in models of inflammation in rodents and nonhuman primates, and in a rat model of postangioplasty restenosis [23,25]. In rats, intramuscular injection of the peptide suppressed subcutaneous recruitment of monocytes and granulocytes induced by LPS.…”