Published online before print October 27, 2005, doi: 10.1161/01.ATV.0000193567.88685.f4
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2006 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Expression of Neutrophil Gelatinase–Associated Lipocalin in Atherosclerosis and Myocardial Infarction
From the Center for Molecular Medicine and Department of Medicine (A.-L.H., A.G., G.K.H.), Karolinska Hospital, Stockholm, Sweden; the Department of Physiology and Pharmacology (A.-L.H., P.T.) and King Gustaf V Research Institute, Department of Medicine, Karolinska Hospital M1 (C.Z., P.E.), Karolinska Institute, Stockholm, Sweden; the Division for Vascular Surgery (U.H.), Department of Surgical Sciences, Karolinska University Hospital, Stockholm, Sweden; and the Cardiac Catheterization Laboratory 2014 (J.K.), The Heart Centre, Rigshospitalet, Copenhagen, Denmark.
Correspondence to Göran K. Hansson, Center for Molecular Medicine L8:03, Karolinska Hospital, SE-171 76, Stockholm, Sweden. E-mail Goran.Hansson{at}cmm.ki.se
Objective— Neutrophil gelatinase-associated lipocalin (NGAL) modulates the activity of matrix metalloproteinase (MMP) 9, an important mediator of vascular remodeling and plaque instability in atherosclerosis. This study aimed to analyze the expression of NGAL in atherosclerotic plaques and myocardial infarction (MI).
Methods and Results— Atherosclerotic apolipoprotein E (apoE)–/– x low-density lipoprotein receptor (LDLR)–/– and C57BL/6J control mice were exposed to brief hypoxic stress (10 minutes of 10% oxygen). Expression of the mouse NGAL homolog (24p3) and MMP-9 was analyzed 48 hours later by quantitative RT-PCR, immunohistochemistry, and zymography. Hypoxic stress increased NGAL/24p3 mRNA in the cardiac vasculature. NGAL/24p3 was also increased in atherosclerotic plaques of apolipoprotein E–/– x LDLR–/– mice compared with C57BL/6J mice. Mice developing MI exhibited the highest plaque mRNA expression of NGAL/24p3 and MMP-9. Zymography revealed strong proteolytic activity in areas rich in 24p3 and MMP-9 protein. Immunohistochemistry performed on human carotid endarterectomy specimens and control tissue from the internal mammary artery showed colocalization of MMP-9 and NGAL with macrophages in the atherosclerotic plaques.
Conclusions— NGAL/24p3 is increased in atherosclerotic plaques and MI. Colocalization with MMP-9 in areas with high-proteolytic activity suggests a role for NGAL/24p3 in modulating the MMP-9-mediated remodeling of plaques and infarcted hearts.
NGAL protects MMP-9 from inactivation but has not been described previously in atherosclerosis. Our study shows that NGAL and its mouse homolog are increased in atherosclerosis and after myocardial infarction and colocalize with MMP-9 in atherosclerotic areas with high-proteolytic activity, suggesting a modulating role for NGAL in atherosclerosis.
Key Words: atherosclerosis • myocardial infarction • hypoxia • matrix metalloproteinase • remodeling
This article has been cited by other articles:
 |
|
 |
|
  A. Yndestad, L. Landro, T. Ueland, C. P. Dahl, T. H. Flo, L. E. Vinge, T. Espevik, S. S. Froland, C. Husberg, G. Christensen, et al. Increased systemic and myocardial expression of neutrophil gelatinase-associated lipocalin in clinical and experimental heart failure Eur. Heart J., May 2, 2009; 30(10): 1229 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. R. Chan, J. S. Liu, D. A. Pociask, M. Zheng, T. A. Mietzner, T. Berger, T. W. Mak, M. C. Clifton, R. K. Strong, P. Ray, et al. Lipocalin 2 Is Required for Pulmonary Host Defense against Klebsiella Infection J. Immunol., April 15, 2009; 182(8): 4947 - 4956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Diamanti-Kandarakis, S. Livadas, S. A Kandarakis, A. Margeli, and I. Papassotiriou Serum concentrations of atherogenic proteins neutrophil gelatinase-associated lipocalin and its complex with matrix metalloproteinase-9 are significantly lower in women with polycystic ovary syndrome: hint of a protective mechanism? Eur. J. Endocrinol., April 1, 2008; 158(4): 525 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K M Choi, J S Lee, E J Kim, S H Baik, H S Seo, D S Choi, D J Oh, and C G Park Implication of lipocalin-2 and visfatin levels in patients with coronary heart disease Eur. J. Endocrinol., February 1, 2008; 158(2): 203 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zernecke, I. Bot, Y. Djalali-Talab, E. Shagdarsuren, K. Bidzhekov, S. Meiler, R. Krohn, A. Schober, M. Sperandio, O. Soehnlein, et al. Protective Role of CXC Receptor 4/CXC Ligand 12 Unveils the Importance of Neutrophils in Atherosclerosis Circ. Res., February 1, 2008; 102(2): 209 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Frank, C. Kuhn, B. Brors, C. Hanselmann, M. Ludde, H. A. Katus, and N. Frey Gene Expression Pattern in Biomechanically Stretched Cardiomyocytes: Evidence for a Stretch-Specific Gene Program Hypertension, February 1, 2008; 51(2): 309 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Bachorzewska-Gajewska, J. Malyszko, E. Sitniewska, J. S. Malyszko, and S. Dobrzycki Neutrophil gelatinase-associated lipocalin (NGAL) correlations with cystatin C, serum creatinine and eGFR in patients with normal serum creatinine undergoing coronary angiography Nephrol. Dial. Transplant., January 1, 2007; 22(1): 295 - 296. [Full Text] [PDF]
|
|
|
|
 |
|
 D.-x. Bu, A.-L. Hemdahl, A. Gabrielsen, J. Fuxe, C. Zhu, P. Eriksson, and Z.-q. Yan Induction of Neutrophil Gelatinase-Associated Lipocalin in Vascular Injury via Activation of Nuclear Factor-{kappa}B Am. J. Pathol., December 1, 2006; 169(6): 2245 - 2253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Garg, M. Rojas, A. Ravi, K. Bockbrader, S. Epstein, M. Vijay-Kumar, A. T. Gewirtz, D. Merlin, and S. V. Sitaraman Selective Ablation of Matrix Metalloproteinase-2 Exacerbates Experimental Colitis: Contrasting Role of Gelatinases in the Pathogenesis of Colitis J. Immunol., September 15, 2006; 177(6): 4103 - 4112. [Abstract] [Full Text] [PDF]
|
|