Expression of neutrophil gelatinase-associated lipocalin in atherosclerosis and myocardial infarction.
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).


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.
Hemdahl
Anne-Louise
AL
Center for Molecular Medicine, Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Gabrielsen
Anders
A
Zhu
Chaoyong
C
Eriksson
Per
P
Hedin
Ulf
U
Kastrup
Jens
J
Thorén
Peter
P
Hansson
Göran K
GK
D000209:Acute-Phase Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D002339:Carotid Arteries / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D000071068:Lipocalin-2; D054834:Lipocalins; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D008323:Mammary Arteries / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics
D000209:Acute-Phase Proteins; D001057:Apolipoproteins E; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011973:Receptors, LDL; C071332:Lcn2 protein, mouse; D020780:Matrix Metalloproteinase 9