Anti-Inflammatory Peptide Approaches for Preventing Vascular Inflammation

• Main Author: Grubb, Sarah Emily Watkins
• Published: University of Sheffield 2007
• Subjects: 616.1
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485211

Coronary heart disease is the leading cause of death in the developed world, and occurs when the coronary arteries become narrowed. It can be treated by angioplasty and/or stent placement. However, in a significant proportion of cases restenosis occurs within the first six months. This is thought to be the body's reaction to the 'injury' of the angioplasty procedure and not the progression of coronary heart disease. Restenosis is a complex problem which is not fully understood, but predominantly involves local inflammation followed by proliferation of vascular smooth muscle (VSMC) and endothelial cells and matrix deposition. The melanocyte stimulating honnone (MSH) peptides are known antiinflammatiories acting via the melanocortin-l receptor (MC-IR). The aim of this project was to investigate the use ofMSH peptides to prevent excessive inflammation of porcine VSMC and endothelial cells with a view to preventing coronary restenosis. This study confinned MC-lR expression on both VSMC and endothelial cells and demonstrates that a-MSH inhibits TNF-a stimulated NF-KB activation in VSMC and E-Selectin upregulation on endothelial cells. In contrast the data also showed that P-Selectin was upregulated by IL-lj3, but not TNF-a and that cytokine stimulation did not cause upregulation of ICAM-l. The data also shows that a-MSH demonstrates a cytoprotective role by improving cellular viability and increases proliferation of VSMC. Furthennore the effect of a-MSH on NF-KB activity in vivo was investigated in a preliminary study using ·a porcine balloon angioplasty model. This study showed that balloon angioplasty increased NF-KB activity and intravenous injection of a-MSH increased NF-KB activity further in a dose responsive manner in VSMC in vivo. In conclusion this research shows that a-MSH inhibits inflammatory signalling in porcine VSMC and endothelial cells. Findings suggest that local delivery of a-MSH may have therapeutic value in the prevention of vascular inflammation but further research is needed.