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High serum TNF-alpha level in Type 2 diabetic patients with microangiopathy is associated with eNOS down-regulation and apoptosis in endothelial cells.
J Diabetes Complications. 2005 Nov-Dec; 19(6):347-55.JD

Abstract

A high dose of tumor necrosis factor (TNF)-alpha induces endothelial dysfunction and enhances apoptosis in vitro. The present study was conducted to examine whether incubating human umbilical vein endothelial cells (HUVECs) with serum from Type 2 diabetic patients complicated with retinopathy and/or microalbuminemia demonstrate endothelial dysfunction. Serum levels of TNF-alpha and vascular endothelial growth factor (VEGF) were elevated in diabetic patients. Plasma levels of TNF-alpha, two soluble TNF-alpha receptors (sTNFR), and VEGF were assessed in diabetic patients (CD, n=21) complicated with retinopathy and/or nephropathy, uncomplicated diabetic patients (UD, n=18), and in healthy normal participants (NS, n=16). In HUVECs incubated with patient's serum, endothelial constitutive nitric oxide synthase (eNOS) protein expressions were measured by Western blot analysis. Apoptosis in HUVECs was determined by optical microscopy, DNA fragmentation, and CPP32-like protease activity. Serum TNF-alpha, sTNFR-I, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NOS, in CD were significantly higher than in UD or NS. While, serum sTNFR-I and VEGF levels were significantly increased in the both diabetic patients, compared with those of NS, no difference was observed in the serum TNF-alpha, sTNFR-II, and ADMA levels between UD and NS. eNOS down-regulation and apoptosis were seen in HUVECs incubated with serum from CD for 24 h, but those observations were completely counteracted in the incubation by the addition of the antihuman TNF-alpha antibody. These results imply that eNOS down-regulation in CD is associated with high serum TNF-alpha levels despite of high serum of VEGF levels. Therefore, endothelial dysfunction in diabetic patients complicated with microangiopathy may, in part, be attributed to high serum TNF-alpha levels.

Authors+Show Affiliations

Makino N
Section of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Beppu 874-0838, Japan. makino@tsurumi.beppu.kyushu-u.ac.jp
Maeda T
No affiliation info available
Sugano M
No affiliation info available
Satoh S
No affiliation info available
Watanabe R
No affiliation info available
Abe N
No affiliation info available

MeSH

AdultAgedApoptosisArginineDiabetes Mellitus, Type 2Diabetic AngiopathiesDown-RegulationEndothelium, VascularFemaleHumansMaleMiddle AgedNitric Oxide Synthase Type IIIReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IISerum AlbuminTumor Necrosis Factor-alphaUmbilical VeinsVascular Endothelial Growth Factor A

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16260352

Citation

Makino, Naoki, et al. "High Serum TNF-alpha Level in Type 2 Diabetic Patients With Microangiopathy Is Associated With eNOS Down-regulation and Apoptosis in Endothelial Cells." Journal of Diabetes and Its Complications, vol. 19, no. 6, 2005, pp. 347-55.
Makino N, Maeda T, Sugano M, et al. High serum TNF-alpha level in Type 2 diabetic patients with microangiopathy is associated with eNOS down-regulation and apoptosis in endothelial cells. J Diabetes Complications. 2005;19(6):347-55.
Makino, N., Maeda, T., Sugano, M., Satoh, S., Watanabe, R., & Abe, N. (2005). High serum TNF-alpha level in Type 2 diabetic patients with microangiopathy is associated with eNOS down-regulation and apoptosis in endothelial cells. Journal of Diabetes and Its Complications, 19(6), 347-55.
Makino N, et al. High Serum TNF-alpha Level in Type 2 Diabetic Patients With Microangiopathy Is Associated With eNOS Down-regulation and Apoptosis in Endothelial Cells. J Diabetes Complications. 2005 Nov-Dec;19(6):347-55. PubMed PMID: 16260352.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High serum TNF-alpha level in Type 2 diabetic patients with microangiopathy is associated with eNOS down-regulation and apoptosis in endothelial cells. AU - Makino,Naoki, AU - Maeda,Toyoki, AU - Sugano,Masahiro, AU - Satoh,Shinji, AU - Watanabe,Reiko, AU - Abe,Nobuyuki, PY - 2005/01/12/received PY - 2005/03/15/revised PY - 2005/04/14/accepted PY - 2005/11/2/pubmed PY - 2006/2/4/medline PY - 2005/11/2/entrez SP - 347 EP - 55 JF - Journal of diabetes and its complications JO - J Diabetes Complications VL - 19 IS - 6 N2 - A high dose of tumor necrosis factor (TNF)-alpha induces endothelial dysfunction and enhances apoptosis in vitro. The present study was conducted to examine whether incubating human umbilical vein endothelial cells (HUVECs) with serum from Type 2 diabetic patients complicated with retinopathy and/or microalbuminemia demonstrate endothelial dysfunction. Serum levels of TNF-alpha and vascular endothelial growth factor (VEGF) were elevated in diabetic patients. Plasma levels of TNF-alpha, two soluble TNF-alpha receptors (sTNFR), and VEGF were assessed in diabetic patients (CD, n=21) complicated with retinopathy and/or nephropathy, uncomplicated diabetic patients (UD, n=18), and in healthy normal participants (NS, n=16). In HUVECs incubated with patient's serum, endothelial constitutive nitric oxide synthase (eNOS) protein expressions were measured by Western blot analysis. Apoptosis in HUVECs was determined by optical microscopy, DNA fragmentation, and CPP32-like protease activity. Serum TNF-alpha, sTNFR-I, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NOS, in CD were significantly higher than in UD or NS. While, serum sTNFR-I and VEGF levels were significantly increased in the both diabetic patients, compared with those of NS, no difference was observed in the serum TNF-alpha, sTNFR-II, and ADMA levels between UD and NS. eNOS down-regulation and apoptosis were seen in HUVECs incubated with serum from CD for 24 h, but those observations were completely counteracted in the incubation by the addition of the antihuman TNF-alpha antibody. These results imply that eNOS down-regulation in CD is associated with high serum TNF-alpha levels despite of high serum of VEGF levels. Therefore, endothelial dysfunction in diabetic patients complicated with microangiopathy may, in part, be attributed to high serum TNF-alpha levels. SN - 1056-8727 UR - https://www.unboundmedicine.com/medline/citation/16260352/High_serum_TNF_alpha_level_in_Type_2_diabetic_patients_with_microangiopathy_is_associated_with_eNOS_down_regulation_and_apoptosis_in_endothelial_cells_ DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓22]

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