BACKGROUND: This investigation tested the hypothesis that L-selectin is important in experimental abdominal aortic aneurysm (AAA) formation in rodents. METHODS AND RESULTS: Rat abdominal aortas were perfused with saline (control) or porcine pancreatic elastase and studied on postperfusion days 1, 2, 4, 7, and 14 (n=5 per treatment group per day). Neutrophil (polymorphonucleur leukocyte, PMN) and macrophage counts per high-powered field (HPF) were performed on fixed sections. L-selectin expression and protein levels in aortic tissue were determined by polymerase chain reaction and Western blot, respectively. Elastase-perfused aortic diameters were significantly increased compared with control aortas at all time points except day 1 (P<0.05). PMN counts significantly increased in elastase-perfused aortas compared with control aortas at days 1, 2, and 4, reaching maximum levels at day 7 (40.8 versus 0.3 PMNs/HPF, P=0.001). L-selectin mRNA expression in elastase-perfused aortas was 18 (P=0.018), 17 (P<0.001), and 8 times (P=0.02) times greater than control aortas at days 1, 2, and 4, respectively. Western blot demonstrated a significant 69% increase in L-selectin protein at day 7 in elastase- as compared with saline-perfused aortas (P=0.005). Subsequent experiments involved similar studies on postperfusion days 4, 7, and 14 of aortas from C57BL/6 wild-type (WT) mice (n=21) and L-selectin-knockout (LKO) mice (n=19). LKO mice had significantly smaller aortic diameters at day 14 as compared with WT mice (88% versus 123%, P=0.02). PMN counts were significantly greater in elastase-perfused WT mouse aortas as compared with LKO mouse aortas at day 4 after perfusion (12.8 versus 4.8 PMNs/HPF, P=0.02). Macrophage counts were significantly greater at all time points after perfusion in elastase-perfused WT mouse aortas compared with elastase-perfused LKO mouse aortas, with a maximum difference at day 7 after perfusion (13.3 versus 0.5 macrophages/HPF, P<0.001). CONCLUSIONS: L-selectin-mediated neutrophil recruitment may be a critical early step in AAA formation.
BACKGROUND: This investigation tested the hypothesis that L-selectin is important in experimental abdominal aortic aneurysm (AAA) formation in rodents. METHODS AND RESULTS:Rat abdominal aortas were perfused with saline (control) or porcine pancreatic elastase and studied on postperfusion days 1, 2, 4, 7, and 14 (n=5 per treatment group per day). Neutrophil (polymorphonucleur leukocyte, PMN) and macrophage counts per high-powered field (HPF) were performed on fixed sections. L-selectin expression and protein levels in aortic tissue were determined by polymerase chain reaction and Western blot, respectively. Elastase-perfused aortic diameters were significantly increased compared with control aortas at all time points except day 1 (P<0.05). PMN counts significantly increased in elastase-perfused aortas compared with control aortas at days 1, 2, and 4, reaching maximum levels at day 7 (40.8 versus 0.3 PMNs/HPF, P=0.001). L-selectin mRNA expression in elastase-perfused aortas was 18 (P=0.018), 17 (P<0.001), and 8 times (P=0.02) times greater than control aortas at days 1, 2, and 4, respectively. Western blot demonstrated a significant 69% increase in L-selectin protein at day 7 in elastase- as compared with saline-perfused aortas (P=0.005). Subsequent experiments involved similar studies on postperfusion days 4, 7, and 14 of aortas from C57BL/6 wild-type (WT) mice (n=21) and L-selectin-knockout (LKO) mice (n=19). LKO mice had significantly smaller aortic diameters at day 14 as compared with WT mice (88% versus 123%, P=0.02). PMN counts were significantly greater in elastase-perfused WT mouse aortas as compared with LKO mouse aortas at day 4 after perfusion (12.8 versus 4.8 PMNs/HPF, P=0.02). Macrophage counts were significantly greater at all time points after perfusion in elastase-perfused WT mouse aortas compared with elastase-perfused LKO mouse aortas, with a maximum difference at day 7 after perfusion (13.3 versus 0.5 macrophages/HPF, P<0.001). CONCLUSIONS:L-selectin-mediated neutrophil recruitment may be a critical early step in AAA formation.
Authors: Paul D DiMusto; Guanyi Lu; Abhijit Ghosh; Karen J Roelofs; Gang Su; Yunge Zhao; Christine L Lau; Omar Sadiq; Brendan McEvoy; Adriana Laser; Jose A Diaz; Thomas W Wakefield; Peter K Henke; Jonathan L Eliason; Gilbert R Upchurch Journal: Am J Physiol Heart Circ Physiol Date: 2012-02-03 Impact factor: 4.733
Authors: Paul D DiMusto; Guanyi Lu; Abhijit Ghosh; Karen J Roelofs; Omar Sadiq; Brendan McEvoy; Gang Su; Adriana Laser; Castigliano M Bhamidipati; Gorav Ailawadi; Peter K Henke; Jonathan L Eliason; Gilbert R Upchurch Journal: J Surg Res Date: 2011-12-14 Impact factor: 2.192
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Authors: Sean J English; Morand R Piert; Jose A Diaz; David Gordon; Abhijit Ghosh; Louis G DʼAlecy; Steven E Whitesall; Ashish K Sharma; Elise P DeRoo; Tessa Watt; Gang Su; Peter K Henke; Jonathan L Eliason; Gorav Ailawadi; Gilbert R Upchurch Journal: Ann Surg Date: 2015-02 Impact factor: 12.969
Authors: Ashish K Sharma; Guanyi Lu; Andrea Jester; William F Johnston; Yunge Zhao; Vanessa A Hajzus; M Reza Saadatzadeh; Gang Su; Castigliano M Bhamidipati; Gaurav S Mehta; Irving L Kron; Victor E Laubach; Michael P Murphy; Gorav Ailawadi; Gilbert R Upchurch Journal: Circulation Date: 2012-09-11 Impact factor: 29.690