Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment
Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is characterized by increased inflammation and an elevated risk for embolization of carotid a...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-08-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12933-017-0579-6 |
| _version_ | 1817995844116283392 |
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| author | W. Eilenberg S. Stojkovic A. Piechota-Polanczyk A. Kaider N. Kozakowski W. J. Weninger J. Nanobachvili J. Wojta I. Huk S. Demyanets C. Neumayer |
| author_facet | W. Eilenberg S. Stojkovic A. Piechota-Polanczyk A. Kaider N. Kozakowski W. J. Weninger J. Nanobachvili J. Wojta I. Huk S. Demyanets C. Neumayer |
| author_sort | W. Eilenberg |
| collection | DOAJ |
| description | Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is characterized by increased inflammation and an elevated risk for embolization of carotid artery stenosis (CAS). We aimed to explore the role of NGAL systemically and in plaques of diabetics undergoing carotid endarterectomy. Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics. Methods Serum NGAL and matrix metalloproteinase (MMP)-9/NGAL levels were measured in 136 patients (67 with T2DM vs. 69 non-diabetics) by specific ELISA. Endarterectomy samples were graded histologically according to the American Heart Association´s classification. NGAL mRNA expression was detected using RealTime-PCR in carotid endarterectomy specimens. Results Serum NGAL [median 107.4 ng/ml (quartiles: 75.2–145.0) vs. 64.4 (50.4 –81.3), p < 0.0001] and MMP-9/NGAL [41.5 ng/ml (20.8–63.9) vs. 27.6 (16.0–42.4), p = 0.017] were significantly elevated in diabetics compared to non-diabetics, as were leukocytes, neutrophils, C-reactive protein and fibrinogen (all p < 0.05). In patients with symptomatic and asymptomatic CAS diabetics had higher NGAL levels compared to non-diabetics [128.8 ng/ml (100.8–195.6) vs. 64.8 (48.9–82.2] and [101.6 ng/ml (70.1–125.3) vs. 63.8 (51.0–81.3), respectively, both p < 0.0001]. Presence of T2DM and type VI plaques (with surface defect, hemorrhage or thrombus) had a profound impact on NGAL levels (both p < 0.01) in multiple linear regression analysis. NGAL mRNA was detectable in 95% of analyzed carotid artery lesions of diabetics compared to 5% of non-diabetics (p < 0.0001). Accordingly, cerebral embolization was more frequent in diabetics (52.2% vs. 29%, p = 0.006). Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9–69.2) vs. 121.7 (103.7–169.9), p < 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1–26.5) vs. 53.7 (27.4–73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics. Conclusions Higher NGAL levels in serum and plaques are associated with T2DM in patients with CAS. Metformin significantly reduced the inflammatory burden including NGAL in diabetics. Early treatment of these patients may be recommended, as elevated NGAL levels were linked with vulnerable plaques prone for embolization. |
| first_indexed | 2024-04-14T02:13:07Z |
| format | Article |
| id | doaj.art-5c01a0fdc6384f21b88933d432efe0bc |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-04-14T02:13:07Z |
| publishDate | 2017-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-5c01a0fdc6384f21b88933d432efe0bc2022-12-22T02:18:21ZengBMCCardiovascular Diabetology1475-28402017-08-0116111110.1186/s12933-017-0579-6Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatmentW. Eilenberg0S. Stojkovic1A. Piechota-Polanczyk2A. Kaider3N. Kozakowski4W. J. Weninger5J. Nanobachvili6J. Wojta7I. Huk8S. Demyanets9C. Neumayer10Department of Surgery, Division of Vascular Surgery, Medical University of ViennaDepartment of Internal Medicine II, Division of Cardiology, Medical University of ViennaDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in KrakowCenter for Medical Statistics, Informatics, and Intelligent Systems, Medical University of ViennaDepartment of Pathology, Medical University of ViennaCenter of Anatomy and Cell Biology, Medical University of ViennaDepartment of Surgery, Division of Vascular Surgery, Medical University of ViennaDepartment of Internal Medicine II, Division of Cardiology, Medical University of ViennaDepartment of Surgery, Division of Vascular Surgery, Medical University of ViennaDepartment of Laboratory Medicine, Medical University of ViennaDepartment of Surgery, Division of Vascular Surgery, Medical University of ViennaAbstract Background Neutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is characterized by increased inflammation and an elevated risk for embolization of carotid artery stenosis (CAS). We aimed to explore the role of NGAL systemically and in plaques of diabetics undergoing carotid endarterectomy. Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics. Methods Serum NGAL and matrix metalloproteinase (MMP)-9/NGAL levels were measured in 136 patients (67 with T2DM vs. 69 non-diabetics) by specific ELISA. Endarterectomy samples were graded histologically according to the American Heart Association´s classification. NGAL mRNA expression was detected using RealTime-PCR in carotid endarterectomy specimens. Results Serum NGAL [median 107.4 ng/ml (quartiles: 75.2–145.0) vs. 64.4 (50.4 –81.3), p < 0.0001] and MMP-9/NGAL [41.5 ng/ml (20.8–63.9) vs. 27.6 (16.0–42.4), p = 0.017] were significantly elevated in diabetics compared to non-diabetics, as were leukocytes, neutrophils, C-reactive protein and fibrinogen (all p < 0.05). In patients with symptomatic and asymptomatic CAS diabetics had higher NGAL levels compared to non-diabetics [128.8 ng/ml (100.8–195.6) vs. 64.8 (48.9–82.2] and [101.6 ng/ml (70.1–125.3) vs. 63.8 (51.0–81.3), respectively, both p < 0.0001]. Presence of T2DM and type VI plaques (with surface defect, hemorrhage or thrombus) had a profound impact on NGAL levels (both p < 0.01) in multiple linear regression analysis. NGAL mRNA was detectable in 95% of analyzed carotid artery lesions of diabetics compared to 5% of non-diabetics (p < 0.0001). Accordingly, cerebral embolization was more frequent in diabetics (52.2% vs. 29%, p = 0.006). Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9–69.2) vs. 121.7 (103.7–169.9), p < 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1–26.5) vs. 53.7 (27.4–73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics. Conclusions Higher NGAL levels in serum and plaques are associated with T2DM in patients with CAS. Metformin significantly reduced the inflammatory burden including NGAL in diabetics. Early treatment of these patients may be recommended, as elevated NGAL levels were linked with vulnerable plaques prone for embolization.http://link.springer.com/article/10.1186/s12933-017-0579-6NGALLipocalinAtherosclerosisCarotid artery stenosisInflammationType II diabetes |
| spellingShingle | W. Eilenberg S. Stojkovic A. Piechota-Polanczyk A. Kaider N. Kozakowski W. J. Weninger J. Nanobachvili J. Wojta I. Huk S. Demyanets C. Neumayer Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment Cardiovascular Diabetology NGAL Lipocalin Atherosclerosis Carotid artery stenosis Inflammation Type II diabetes |
| title | Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment |
| title_full | Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment |
| title_fullStr | Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment |
| title_full_unstemmed | Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment |
| title_short | Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment |
| title_sort | neutrophil gelatinase associated lipocalin ngal is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment |
| topic | NGAL Lipocalin Atherosclerosis Carotid artery stenosis Inflammation Type II diabetes |
| url | http://link.springer.com/article/10.1186/s12933-017-0579-6 |
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