Table 1.
Summary of animal studies on NGAL and cardiovascular disease.
| Reference | Animal model | Specimen | Analysis | Molecule | Major findings |
|---|---|---|---|---|---|
| Hemdahl (7) | apoE-/- × LDLR-/-(atherosclerotic mice) and C57BL/6J (control mice) exposed to hypoxic stress | Aortic plaque | mRNA expression | NGAL/24p3 | Baseline: Atherosclerotic mice (Ath) > control mice (Con). After hypoxic stress: Ath who suffered MI (Ath-MI) > Ath-no MI. |
| MMP-9 | After hypoxic stress: Ath-MI > Ath-no MI. | ||||
| Immunohistochemistry | NGAL/24p3 and MMP-9 | Abundant NGAL protein co-localized with MMP-9 in Ath. No NGAL or MMP-9 demonstrated in Con. |
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| Myocardium | mRNA expression | NGAL/24p3 | Baseline: Ath=Con. After hypoxic stress: ↑ in both Ath and Con; greatest ↑ seen in Ath-MI. |
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| MMP-9 | Baseline: Ath > Con. After hypoxic stress: ↑ only in Con; no change in Ath. |
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| Immunohistochemistry | NGAL/24p3 and MMP-9 | NGAL protein co-localized with MMP-9 in cardiomyocytes of Ath. No NGAL or MMP-9 demonstrated in Con. |
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| Yndestadt (9) | Wistar rats undergoing ligation of left coronary artery or sham operation | Heart ventricle | mRNA expression | NGAL/24p3 | Rats with HF had ↑NGAL expression in the non-ischemic area of the ventricle 2, 7, 28, and 64 days after the induction of MI. This upregulation was demonstrated in cardiomyocytes, but not in fibroblasts or endothelial cells. |
| Ding (13) | Lewis rats immunized with porcine cardiac myosin (EAM) and control rats | Heart ventricle | mRNA expression | Lcn2/NGAL | In EAM rat hearts, NGAL expression started to rise after 9 days, peaked on days 12–18, and returned to near-baseline levels at day 60. This upregulation was demonstrated in cardiomyocytes, endothelial cells, pericytes, smooth muscle cells and fibroblasts. This increase was not seen in control rats. |
| Immunohistochemistry | Lcn2/NGAL | In EAM rat hearts, NGAL immunostaining was seen in cardiomyocytes, vascular smooth muscle cells, fibroblastoid cells, and leukocytes. This was hardly detected in control rat hearts. |
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| Plasma | ELISA | Lcn2/NGAL, IL-1β, BNP | In EAM rats, NGAL and IL-1β levels increased at day 13, remained elevated at day 33, and returned to near-baseline levels after day 45. | ||
| Bu (14) | Sprague-Dawley rats subjected to balloon injury of the left common carotid artery | Carotid artery | mRNA expression | NGAL, MMP-9 | Angioplastic injury to the artery induced high expression of NGAL mRNA at day 14 but not at day 3. MMP-9 was markedly upregulated in the vessels shortly after injury. Blocking of NF-κB resulted in virtually complete suppression of NGAL and MMP-9 expression. |
| te Boekhorst (15) | ApoE2/2/eNOS2/2 mice were injected with NGAL/24p3-targeted micelles | Abdominal aorta | Histology and MRI | NGAL/24p3 | NGAL can be detected in murine atherosclerotic arteries using targeted high-resolution MRI. |
EAM, experimental autoimmune myocarditis.