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Peptide Inhibitor of CXCL4–CCL5 Heterodimer Formation, MKEY, Inhibits Experimental Aortic Aneurysm Initiation and Progression

Peptide Inhibitor of CXCL4–CCL5 Heterodimer Formation, MKEY, Inhibits Experimental Aortic... Peptide Inhibitor of CXCL4–CCL5 Heterodimer Formation, MKEY, Inhibits Experimental Aortic Aneurysm Initiation and Progression Yasunori Iida,* Baohui Xu,* Haojun Xuan, Keith J. Glover, Hiroki Tanaka, Xiaolei Hu, Naoki Fujimura, Wei Wang, Joshua R. Schultz, Court R. Turner, Ronald L. Dalman Objective—Macrophages are critical contributors to abdominal aortic aneurysm (AAA) disease. We examined the ability of MKEY, a peptide inhibitor of CXCL4–CCL5 interaction, to influence AAA progression in murine models. Approach and Results—AAAs were created in 10-week-old male C57BL/6J mice by transient infrarenal aortic porcine pancreatic elastase infusion. Mice were treated with MKEY via intravenous injection either (1) before porcine pancreatic elastase infusion or (2) after aneurysm initiation. Immunostaining demonstrated CCL5 and CCR5 expression on aneurysmal aortae and mural monocytes/macrophages, respectively. MKEY treatment partially inhibited migration of adaptively transferred leukocytes into aneurysmal aortae in recipient mice. Although all vehicle-pretreated mice developed AAAs, aneurysms formed in only 60% (3/5) and 14% (1/7) of mice pretreated with MKEY at 10 and 20 mg/kg, respectively. MKEY pretreatment reduced aortic diameter enlargement, preserved medial elastin fibers and smooth muscle cells, and attenuated mural macrophage infiltration, angiogenesis, and aortic metalloproteinase 2 and 9 expression after porcine pancreatic elastase infusion. MKEY initiated after porcine pancreatic elastase http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arteriosclerosis, Thrombosis, and Vascular Biology Wolters Kluwer Health

Peptide Inhibitor of CXCL4–CCL5 Heterodimer Formation, MKEY, Inhibits Experimental Aortic Aneurysm Initiation and Progression

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Copyright
© 2013 American Heart Association, Inc.
ISSN
1079-5642
eISSN
1524-4636
DOI
10.1161/ATVBAHA.112.300329
pmid
23288157
Publisher site
See Article on Publisher Site

Abstract

Peptide Inhibitor of CXCL4–CCL5 Heterodimer Formation, MKEY, Inhibits Experimental Aortic Aneurysm Initiation and Progression Yasunori Iida,* Baohui Xu,* Haojun Xuan, Keith J. Glover, Hiroki Tanaka, Xiaolei Hu, Naoki Fujimura, Wei Wang, Joshua R. Schultz, Court R. Turner, Ronald L. Dalman Objective—Macrophages are critical contributors to abdominal aortic aneurysm (AAA) disease. We examined the ability of MKEY, a peptide inhibitor of CXCL4–CCL5 interaction, to influence AAA progression in murine models. Approach and Results—AAAs were created in 10-week-old male C57BL/6J mice by transient infrarenal aortic porcine pancreatic elastase infusion. Mice were treated with MKEY via intravenous injection either (1) before porcine pancreatic elastase infusion or (2) after aneurysm initiation. Immunostaining demonstrated CCL5 and CCR5 expression on aneurysmal aortae and mural monocytes/macrophages, respectively. MKEY treatment partially inhibited migration of adaptively transferred leukocytes into aneurysmal aortae in recipient mice. Although all vehicle-pretreated mice developed AAAs, aneurysms formed in only 60% (3/5) and 14% (1/7) of mice pretreated with MKEY at 10 and 20 mg/kg, respectively. MKEY pretreatment reduced aortic diameter enlargement, preserved medial elastin fibers and smooth muscle cells, and attenuated mural macrophage infiltration, angiogenesis, and aortic metalloproteinase 2 and 9 expression after porcine pancreatic elastase infusion. MKEY initiated after porcine pancreatic elastase

Journal

Arteriosclerosis, Thrombosis, and Vascular Biology – Wolters Kluwer Health

Published: Apr 1, 2013

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