Induction of Monocyte Chemoattractant Protein-1 in the Small Veins of the Ischemic and Reperfused Canine Myocardium

作者：Ajith G. Kumar, Christie Mitchell Ballantyne, Lloyd H. Michael, Gilbert L. Kukielka, Keith A. Youker, Merry L. Lindsey, Hal K. Hawkins, Holly H. Birdsall, Charles Reay Mackay, Gregory J. LaRosa, Roger D. Rossen, C. Wayne Smith, Mark L. Entman · 发表于：Circulation · 年份：1997 · DOI：10.1161/01.cir.95.3.693 · 被引用次数：176 · 研究领域：Cardiac Fibrosis and Remodeling、Cardiac Ischemia and Reperfusion、Chemokine receptors and signaling

BACKGROUND: Healing after myocardial infarction is characterized by the presence of macrophages in the infarcted area. Since augmented monocyte influx has been implicated as a potential mechanism for improved healing after reperfusion, we wished to study the induction of monocyte chemoattractant protein-1 (MCP-1) during reperfusion. METHODS AND RESULTS: The cDNA for MCP-1 was cloned from a canine jugular vein endothelial cell (CJVEC) library and exhibited 78% identity with the deduced amino acid sequence of human MCP-1. Samples of myocardium were taken from control and ischemic segments after 1 hour of ischemia and various times of reperfusion; total RNA was isolated from myocardial samples and probed with a cDNA probe for canine MCP-1. Induction of MCP-1 mRNA occurred only in previously ischemic segments within the first hour of reperfusion, peaked at 3 hours, and persisted throughout the first 2 days of reperfusion. In the absence of reperfusion, no significant MCP-1 induction was seen. Both ischemic (but not preischemic) cardiac lymph and human recombinant TNF-alpha induced MCP-1 in CJVECs. MCP-1 was identified by immunostaining on infiltrating cells and venular (but not arterial) endothelium by 3 hours. In contrast, in situ hybridization showed MCP-1 mRNA to be confined to the endothelium of small veins (venules) 10 to 70 microns in diameter. CONCLUSIONS: MCP-1 mRNA is induced in the endothelium of a specific class of small veins immediately after reperfusion. MCP-1 induc...