Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice (Nat Med, 2009, 15:97-103)

報告日期: 2009/04/21
報告時間: 16:05/16:55
報告學生: 張玲華
講評老師: 蔡佩珍
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980421-2.pdf

Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice

NATURE MEDICINE VOLUME 15   NUMBER 1  JANUARY 2009

 

Speaker: Ling-Hua Chang (張玲華)

Commentator: Dr. Pei-Jane Tsai (Dr. 蔡佩珍)

Date: 2009-04-21() 16:05-16:55

Place: Room602

 

Abstract:

   Atherosclerosis is a chronic disorder of the arterial wall that starts by the formation of a fatty streak, which is an accumulation of lipid-load macrophages in the intiman and caused dysfunction of endothelial cell. This local endothelial-cell defect promotes the adhesion of leukocytes and activated platelets. Activated platelets can secrete chemokines to promote atherogenesis, such as CXCL4 (PF4) and CCL5 (RANTES). Heterodimerization of CCL5 and CXCL4 recruit monocyte to arrest on inflamed endothelium and promoting atherosclerosis has been reported recently. Thus, author attempted to design a peptide antagonist that would attenuate heterodimer formation. They found a peptide termed ‘CKEY2’, comprising from CCL5 residues 25-44 and its N- and C- termini which can form a cycle to become stable. CKEY2 can compete with CXCL4 for binding to CCL5 and specifically disrupt proinflammatory CCL5-CXCL4 interaction and reducing atherosclerosis. Besides, the most importance of this CCL5 antagonist is it without side effects of severely compromise systemic immune response, delay macrophage-mediated viral clearance and impairs normal T cell functions. Finally, they evaluated peptide antagonist and show the potential of targeting heteromer formation in vivo to achieve therapeutic effects. 

 

Referance:

1. Hansson, G.K. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 352, 1685–1695 (2005).

2. Weber, C., Zernecke, A. & Libby, P. The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models. Nat. Rev. Immunol. 8, 802–815 (2008).