Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction

被引:148
作者
Lindsey, ML
Escobar, GP
Dobrucki, LW
Goshorn, DK
Bouges, S
Mingoia, JT
McClister, DM
Su, HL
Gannon, J
MacGillivray, C
Lee, RT
Sinusas, AJ
Spinale, FG
机构
[1] Med Univ S Carolina, Div Cardiothorac Surg Res, Charleston, SC 29425 USA
[2] Yale Univ, Sch Med, Div Cardiovasc Med, Dept Internal Med, New Haven, CT USA
[3] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA
[4] Brigham & Womens Hosp, Div Cardiovasc, Dept Med, Cambridge, MA USA
[5] Harvard Univ, Sch Med, Cambridge, MA 02138 USA
[6] Ralph A Johnson Vet Adm Med Ctr, Charleston, SC USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2006年 / 290卷 / 01期
关键词
leukocytes; remodeling; imaging;
D O I
10.1152/ajpheart.00457.2005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Matrix metalloproteinases (MMPs) are postulated to be necessary for during wound healing. MMP- 9 deletion alters remodeling postmyocardial infarction (post-MI), but whether and to what degree MMP-9 affects neovascularization post-MI is unknown. Neovascularization was evaluated in wild-type (WT; n = 63) and MMP-9 null (n = 55) mice at 7-days post-MI. Despite similar infarct sizes, MMP-9 deletion improved left ventricular function as evaluated by hemodynamic analysis. Blood vessel quantity and quality were evaluated by three independent studies. First, vessel density was increased in the infarct of MMP-9 null mice compared with WT, as quantified by Griffonia (Bandeiraea) simplicifolia lectin I (GSL-I) immunohistochemistry. Second, preexisting vessels, stained in vivo with FITC-labeled GSL-I pre-MI, were present in the viable but not MI region. Third, a technetium-99m-labeled peptide (NC100692), which selectively binds to activated alpha(v)beta(3)-integrin in angiogenic vessels, was injected into post- MI mice. Relative NC100692 activity in myocardial segments with diminished perfusion (0 - 40% nonischemic) was higher in MMP-9 null than in WT mice (383 +/- 162% vs. 250 +/- 118%, respectively; P = 0.002). The unique finding of this study was that MMP-9 deletion stimulated, rather than impaired, neovascularization in remodeling myocardium. Thus targeted strategies to inhibit MMP-9 early post-MI will likely not impair the angiogenic response.
引用
收藏
页码:H232 / H239
页数:8
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