SIALYL LEWIS(X)-CONTAINING OLIGOSACCHARIDE ATTENUATES MYOCARDIAL REPERFUSION INJURY IN CATS

被引:174
作者
BUERKE, M
WEYRICH, AS
ZHENG, ZL
GAETA, FCA
FORREST, MJ
LEFER, AM
机构
[1] THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PHYSIOL,PHILADELPHIA,PA 19107
[2] CYTEL CORP,SAN DIEGO,CA 92121
关键词
ENDOTHELIAL DYSFUNCTION; MYOCARDIAL REPERFUSION INJURY; NEUTROPHIL ADHERENCE; SELECTINS;
D O I
10.1172/JCI117066
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Neutrophil(PMN) adhesion to the vascular endothelium is an important mechanism of myocardial reperfusion injury. The adhesion process is initially mediated by selectins (e.g., P- and L-selectin), and monoclonal antibodies directed against these adhesion molecules exert cardioprotective activity in ischemia/reperfusion models. The counterreceptors for these selectins are thought to be carbohydrate-containing moieties. In this connection, we studied the effect of a soluble sialyl Lewis(x)-containing oligosaccharide (SLe(x)-OS) on PMN-endothelial interactions in a feline model of myocardial ischemia/reperfusion (MI/R). SLe(x)-OS (10 mg/kg), administered 10 min before R, significantly reduced myocardial necrosis compared with its vehicle 270 min after reperfusion (6 +/- 1% vs. 35 +/- 4% of area at risk, P < 0.01). The cardioprotection was confirmed by significantly lower plasma creatine kinase activities in SLe(x)-OS vs. vehicle-treated cats (P < 0.01). Cardiac contractility (dP/dt max) of cats receiving SLe(x)-OS was significantly preserved after 270 min of R (97 +/- 2% vs. 78 +/- 5% of initial, P < 0.01). Furthermore, endothelium-dependent relaxation to acetylcholine in coronary artery rings isolated from MI/R cats treated with SLe(x)-OS was significantly preserved (73 +/- 7% vs. 22 +/- 6% vasorelaxation, P < 0.01). In vitro PR adherence to coronary vascular endothelium after 270 min of R was significantly attenuated in the SLe(x)-OS-treated group compared with the vehicle group (14 +/- 5 vs. 91 +/- 12 PMN/mm(2), P < 0.01). Our results indicate that a SLe(x)-OS is cardioprotective and preserves coronary endothelial function after MI/R, indicating an important role of sialyl Lewis(x) in PR-IN accumulation, endothelial dysfunction, and myocardial injury in myocardial ischemia/reperfusion.
引用
收藏
页码:1140 / 1148
页数:9
相关论文
共 43 条
[1]   IDENTIFICATION OF AN INDUCIBLE ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE [J].
BEVILACQUA, MP ;
POBER, JS ;
MENDRICK, DL ;
COTRAN, RS ;
GIMBRONE, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (24) :9238-9242
[2]   SELECTINS [J].
BEVILACQUA, MP ;
NELSON, RM .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (02) :379-387
[3]   MARKED REDUCTION OF FREE-RADICAL GENERATION AND CONTRACTILE DYSFUNCTION BY ANTIOXIDANT THERAPY BEGUN AT THE TIME OF REPERFUSION - EVIDENCE THAT MYOCARDIAL STUNNING IS A MANIFESTATION OF REPERFUSION INJURY [J].
BOLLI, R ;
JEROUDI, MO ;
PATEL, BS ;
ARUOMA, OI ;
HALLIWELL, B ;
LAI, EK ;
MCCAY, PB .
CIRCULATION RESEARCH, 1989, 65 (03) :607-622
[4]  
Brandley B K, 1991, Semin Cell Biol, V2, P281
[5]  
BRAUNWALD E, 1976, PATHOPHYSIOLOGY THER, P265
[6]   THE SELECTIN FAMILY OF CARBOHYDRATE-BINDING PROTEINS - STRUCTURE AND IMPORTANCE OF CARBOHYDRATE LIGANDS FOR CELL-ADHESION [J].
CUMMINGS, RD ;
SMITH, DF .
BIOESSAYS, 1992, 14 (12) :849-856
[7]   ROLE OF LEUKOCYTES IN RESPONSE TO ACUTE MYOCARDIAL-ISCHEMIA AND REFLOW IN DOGS [J].
ENGLER, RL ;
DAHLGREN, MD ;
MORRIS, DD ;
PETERSON, MA ;
SCHMIDSCHONBEIN, GW .
AMERICAN JOURNAL OF PHYSIOLOGY, 1986, 251 (02) :H314-H323
[8]   MYOCARDIAL INFARCT EXTENSION DURING REPERFUSION AFTER CORONARY-ARTERY OCCLUSION - PATHOLOGICAL EVIDENCE [J].
FARB, A ;
KOLODGIE, FD ;
JENKINS, M ;
VIRMANI, R .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1993, 21 (05) :1245-1253
[9]  
FORMAN MB, 1990, CIRCULATION, V81, P69
[10]   THE 3 MEMBERS OF THE SELECTIN RECEPTOR FAMILY RECOGNIZE A COMMON CARBOHYDRATE EPITOPE, THE SIALYL LEWIS OLIGOSACCHARIDE [J].
FOXALL, C ;
WATSON, SR ;
DOWBENKO, D ;
FENNIE, C ;
LASKY, LA ;
KISO, M ;
HASEGAWA, A ;
ASA, D ;
BRANDLEY, BK .
JOURNAL OF CELL BIOLOGY, 1992, 117 (04) :895-902