Calcium dobesilate may alleviate diabetes‑induced endothelial dysfunction and inflammation
Yijun Zhou, Jiangzi Yuan, Chaojun Qi, Xinghua Shao, Shan Mou, Zhaohui Ni, Yijun Zhou, Jiangzi Yuan, Chaojun Qi, Xinghua Shao, Shan Mou, Zhaohui Ni
Abstract
Diabetic kidney disease (DKD) is a leading cause of end‑stage renal disease. However, the pathogenesis of DKD remains unclear, and no effective treatments for the disease are available. Thus, there is an urgent need to elucidate the pathogenic mechanisms of DKD and to develop more effective therapies for this disease. Human umbilical vein endothelial cells (HUVECs) were cultured using different D‑glucose concentrations to determine the effect of high glucose (HG) on the cells. Alternatively, HUVECs were incubated with 100 µmol/l calcium dobesilate (CaD) to detect its effects. The authors subsequently measured HUVEC proliferation via cell counting kit‑8 assays. In addition, HUVEC angiogenesis was investigated via migration assays and fluorescein isothiocyanate (FITC)‑labelled bovine serum albumin (BSA) permeability assays. The content or distribution of markers of endothelial dysfunction [vascular endothelial growth factor (VEGF), VEGF receptor (R) and endocan) or inflammation [intercellular adhesion molecule (ICAM)‑1, monocyte chemotactic protein (MCP)‑1 and pentraxin‑related protein (PTX3)] was evaluated via reverse transcription‑quantitative polymerase chain reaction and western blotting. HG treatment induced increased in VEGF, VEGFR, endocan, ICAM‑1, MCP‑1 and PTX3 mRNA and protein expression in HUVECs. HG treatment for 24 to 48 h increased cell proliferation in a time‑dependent manner, but the cell proliferation rate was decreased at 72 h of HG treatment. Conversely, CaD inhibited abnormal cell proliferation. HG treatment also significantly enhanced HVUEC migration compared to the control treatment. In contrast, CaD treatment partially inhibited HUVEC migration compared to HG exposure. HG‑treated HUVECs exhibited increased FITC‑BSA permeability compared to control cells cultured in medium alone; however, CaD application prevented the HG‑induced increase in FITC‑BSA permeability and suppressed HG‑induced overexpression of endothelial markers (VEGF, VEGFR‑2, endocan) and inflammation markers (ICAM‑1, MCP‑1, PTX3) in HUVECs. CaD has angioprotective properties and protects endothelial cells partly by ameliorating HG‑induced inflammation. The current results demonstrated the potential applicability of CaD to the treatment of diabetic nephropathy, particularly during the early stages of this disease.
Figures
![Figure 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5779917/bin/MMR-16-06-8635-g00.jpg)
Figure 2.
Western blot analysis of VEGF,…
Figure 2.
Western blot analysis of VEGF, VEGFR, endocan, ICAM, MCP-1 and PTX3 protein expression.…
Figure 3.
Effects of different cell treatments…
Figure 3.
Effects of different cell treatments on HUVEC proliferation. Cell Counting kit-8 assay was…
Figure 4.
CaD prevents migration of HUVECs,…
Figure 4.
CaD prevents migration of HUVECs, which partially induced by diabetes or HG. Transwell…
Figure 5.
HG increased the permeability of…
Figure 5.
HG increased the permeability of HUVECs, which inhibited by CaD. Permeability assay analysing…
Figure 6.
HG (35 mmol/l) increased the…
Figure 6.
HG (35 mmol/l) increased the mRNA levels of VEGF, VEGFR-2, endocan in a…
Figure 7.
HG (35 mmol/l) increased the…
Figure 7.
HG (35 mmol/l) increased the protein levels of VEGF, VEGFR-2, endocan in a…
- Investigation of the Mechanism Underlying Calcium Dobesilate-Mediated Improvement of Endothelial Dysfunction and Inflammation Caused by High Glucose.Zhou Y, Qi C, Li S, Shao X, Ni Z. Zhou Y, et al. Mediators Inflamm. 2019 Oct 21;2019:9893682. doi: 10.1155/2019/9893682. eCollection 2019. Mediators Inflamm. 2019. PMID: 31780874 Free PMC article.
- Diabetic Nephropathy Can Be Treated with Calcium Dobesilate by Alleviating the Chronic Inflammatory State and Improving Endothelial Cell Function.Zhou Y, Qi C, Li S, Shao X, Mou S, Ni Z. Zhou Y, et al. Cell Physiol Biochem. 2018;51(3):1119-1133. doi: 10.1159/000495491. Epub 2018 Nov 26. Cell Physiol Biochem. 2018. PMID: 30476916 Clinical Trial.
- ROCK inhibitor fasudil attenuated high glucose-induced MCP-1 and VCAM-1 expression and monocyte-endothelial cell adhesion.Li H, Peng W, Jian W, Li Y, Li Q, Li W, Xu Y. Li H, et al. Cardiovasc Diabetol. 2012 Jun 13;11:65. doi: 10.1186/1475-2840-11-65. Cardiovasc Diabetol. 2012. PMID: 22694757 Free PMC article. Clinical Trial.
- Calcium dobesilate reduces VEGF signaling by interfering with heparan sulfate binding site and protects from vascular complications in diabetic mice.Njau F, Shushakova N, Schenk H, Wulfmeyer VC, Bollin R, Menne J, Haller H. Njau F, et al. PLoS One. 2020 Jan 14;15(1):e0218494. doi: 10.1371/journal.pone.0218494. eCollection 2020. PLoS One. 2020. PMID: 31935212 Free PMC article.
- Calcium Dobesilate and Micro-vascular diseases.Liu J, Li S, Sun D. Liu J, et al. Life Sci. 2019 Mar 15;221:348-353. doi: 10.1016/j.lfs.2019.02.023. Epub 2019 Feb 12. Life Sci. 2019. PMID: 30769115 Review.
- Intravitreal Ranibizumab Alone or in Combination with Calcium Dobesilate for the Treatment of Diabetic Macular Edema in Nonproliferative Diabetic Retinopathy Patients: 12-Month Outcomes of a Retrospective Study.Wang D, Wang H, Wu S, Yang X, Xu J. Wang D, et al. Int J Clin Pract. 2022 Oct 20;2022:6725225. doi: 10.1155/2022/6725225. eCollection 2022. Int J Clin Pract. 2022. PMID: 36340967 Free PMC article. Review.
- An In Vitro Model of Diabetic Retinal Vascular Endothelial Dysfunction and Neuroretinal Degeneration.Wang Q, Zhang X, Wang K, Zhu L, Qiu B, Chen X, Lin X, Nie Y. Wang Q, et al. J Diabetes Res. 2021 Nov 10;2021:9765119. doi: 10.1155/2021/9765119. eCollection 2021. J Diabetes Res. 2021. PMID: 34805414 Free PMC article.
- Effect of Calcium Dobesilate in Preventing Contrast-Induced Nephropathy in Patients with Diabetes and Chronic Kidney Disease.Zhang H, Guo SH, Xue ZK, Zhang YR, Wang JR, Che JJ, Liu T, Tao HY, Li GP, Rha SW, Ashraful-Haque SZ, Chen KY. Zhang H, et al. Clinics (Sao Paulo). 2021 Oct 18;76:e2942. doi: 10.6061/clinics/2021/e2942. eCollection 2021. Clinics (Sao Paulo). 2021. PMID: 34669873 Free PMC article.
- MiR-302a Limits Vascular Inflammation by Suppressing Nuclear Factor-κ B Pathway in Endothelial Cells.Yuan JN, Hong Y, Ma ZL, Pang RP, Lei QQ, Lv XF, Zhou JG, Huang H, Zhang TT. Yuan JN, et al. Front Cell Dev Biol. 2021 Aug 2;9:682574. doi: 10.3389/fcell.2021.682574. eCollection 2021. Front Cell Dev Biol. 2021. PMID: 34409030 Free PMC article.
- Calcium Dobesilate Reverses Cognitive Deficits and Anxiety-Like Behaviors in the D-Galactose-Induced Aging Mouse Model through Modulation of Oxidative Stress.Hakimizadeh E, Zamanian M, Giménez-Llort L, Sciorati C, Nikbakhtzadeh M, Kujawska M, Kaeidi A, Hassanshahi J, Fatemi I. Hakimizadeh E, et al. Antioxidants (Basel). 2021 Apr 23;10(5):649. doi: 10.3390/antiox10050649. Antioxidants (Basel). 2021. PMID: 33922431 Free PMC article.
-
- International Diabetes Federation, corp-author. www.diabetesatlas.org Diabetes Atlas. (7th edition) 2015
- Biomarkers / metabolism
- C-Reactive Protein / metabolism
- Calcium Dobesilate / pharmacology
- Calcium Dobesilate / therapeutic use*
- Cell Membrane Permeability / drug effects
- Cell Movement / drug effects
- Cell Proliferation / drug effects
- Chemokine CCL2 / metabolism
- Diabetes Mellitus / drug therapy*
- Diabetes Mellitus / pathology
- Diabetes Mellitus / physiopathology*
- Endothelium, Vascular / drug effects
- Endothelium, Vascular / pathology*
- Endothelium, Vascular / physiopathology*
- Glucose / toxicity
- Human Umbilical Vein Endothelial Cells / drug effects
- Human Umbilical Vein Endothelial Cells / metabolism
- Humans
- Inflammation / pathology*
- Inflammation Mediators / metabolism
- Intercellular Adhesion Molecule-1 / metabolism
- Neoplasm Proteins / genetics
- Neoplasm Proteins / metabolism
- Proteoglycans / genetics
- Proteoglycans / metabolism
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Serum Amyloid P-Component / metabolism
- Time Factors
- Up-Regulation / drug effects
- Vascular Endothelial Growth Factor A / genetics
- Vascular Endothelial Growth Factor A / metabolism
- Vascular Endothelial Growth Factor Receptor-2 / genetics
- Vascular Endothelial Growth Factor Receptor-2 / metabolism
- Biomarkers
- Chemokine CCL2
- ESM1 protein, human
- Inflammation Mediators
- Neoplasm Proteins
- Proteoglycans
- RNA, Messenger
- Serum Amyloid P-Component
- Vascular Endothelial Growth Factor A
- Intercellular Adhesion Molecule-1
- PTX3 protein
- Calcium Dobesilate
- C-Reactive Protein
- Vascular Endothelial Growth Factor Receptor-2
- Glucose
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5779917/bin/MMR-16-06-8635-g01.jpg)
Figure 3.
Effects of different cell treatments…
Figure 3.
Effects of different cell treatments on HUVEC proliferation. Cell Counting kit-8 assay was…
Figure 4.
CaD prevents migration of HUVECs,…
Figure 4.
CaD prevents migration of HUVECs, which partially induced by diabetes or HG. Transwell…
Figure 5.
HG increased the permeability of…
Figure 5.
HG increased the permeability of HUVECs, which inhibited by CaD. Permeability assay analysing…
Figure 6.
HG (35 mmol/l) increased the…
Figure 6.
HG (35 mmol/l) increased the mRNA levels of VEGF, VEGFR-2, endocan in a…
Figure 7.
HG (35 mmol/l) increased the…
Figure 7.
HG (35 mmol/l) increased the protein levels of VEGF, VEGFR-2, endocan in a…
- Investigation of the Mechanism Underlying Calcium Dobesilate-Mediated Improvement of Endothelial Dysfunction and Inflammation Caused by High Glucose.Zhou Y, Qi C, Li S, Shao X, Ni Z. Zhou Y, et al. Mediators Inflamm. 2019 Oct 21;2019:9893682. doi: 10.1155/2019/9893682. eCollection 2019. Mediators Inflamm. 2019. PMID: 31780874 Free PMC article.
- Diabetic Nephropathy Can Be Treated with Calcium Dobesilate by Alleviating the Chronic Inflammatory State and Improving Endothelial Cell Function.Zhou Y, Qi C, Li S, Shao X, Mou S, Ni Z. Zhou Y, et al. Cell Physiol Biochem. 2018;51(3):1119-1133. doi: 10.1159/000495491. Epub 2018 Nov 26. Cell Physiol Biochem. 2018. PMID: 30476916 Clinical Trial.
- ROCK inhibitor fasudil attenuated high glucose-induced MCP-1 and VCAM-1 expression and monocyte-endothelial cell adhesion.Li H, Peng W, Jian W, Li Y, Li Q, Li W, Xu Y. Li H, et al. Cardiovasc Diabetol. 2012 Jun 13;11:65. doi: 10.1186/1475-2840-11-65. Cardiovasc Diabetol. 2012. PMID: 22694757 Free PMC article. Clinical Trial.
- Calcium dobesilate reduces VEGF signaling by interfering with heparan sulfate binding site and protects from vascular complications in diabetic mice.Njau F, Shushakova N, Schenk H, Wulfmeyer VC, Bollin R, Menne J, Haller H. Njau F, et al. PLoS One. 2020 Jan 14;15(1):e0218494. doi: 10.1371/journal.pone.0218494. eCollection 2020. PLoS One. 2020. PMID: 31935212 Free PMC article.
- Calcium Dobesilate and Micro-vascular diseases.Liu J, Li S, Sun D. Liu J, et al. Life Sci. 2019 Mar 15;221:348-353. doi: 10.1016/j.lfs.2019.02.023. Epub 2019 Feb 12. Life Sci. 2019. PMID: 30769115 Review.
- Intravitreal Ranibizumab Alone or in Combination with Calcium Dobesilate for the Treatment of Diabetic Macular Edema in Nonproliferative Diabetic Retinopathy Patients: 12-Month Outcomes of a Retrospective Study.Wang D, Wang H, Wu S, Yang X, Xu J. Wang D, et al. Int J Clin Pract. 2022 Oct 20;2022:6725225. doi: 10.1155/2022/6725225. eCollection 2022. Int J Clin Pract. 2022. PMID: 36340967 Free PMC article. Review.
- An In Vitro Model of Diabetic Retinal Vascular Endothelial Dysfunction and Neuroretinal Degeneration.Wang Q, Zhang X, Wang K, Zhu L, Qiu B, Chen X, Lin X, Nie Y. Wang Q, et al. J Diabetes Res. 2021 Nov 10;2021:9765119. doi: 10.1155/2021/9765119. eCollection 2021. J Diabetes Res. 2021. PMID: 34805414 Free PMC article.
- Effect of Calcium Dobesilate in Preventing Contrast-Induced Nephropathy in Patients with Diabetes and Chronic Kidney Disease.Zhang H, Guo SH, Xue ZK, Zhang YR, Wang JR, Che JJ, Liu T, Tao HY, Li GP, Rha SW, Ashraful-Haque SZ, Chen KY. Zhang H, et al. Clinics (Sao Paulo). 2021 Oct 18;76:e2942. doi: 10.6061/clinics/2021/e2942. eCollection 2021. Clinics (Sao Paulo). 2021. PMID: 34669873 Free PMC article.
- MiR-302a Limits Vascular Inflammation by Suppressing Nuclear Factor-κ B Pathway in Endothelial Cells.Yuan JN, Hong Y, Ma ZL, Pang RP, Lei QQ, Lv XF, Zhou JG, Huang H, Zhang TT. Yuan JN, et al. Front Cell Dev Biol. 2021 Aug 2;9:682574. doi: 10.3389/fcell.2021.682574. eCollection 2021. Front Cell Dev Biol. 2021. PMID: 34409030 Free PMC article.
- Calcium Dobesilate Reverses Cognitive Deficits and Anxiety-Like Behaviors in the D-Galactose-Induced Aging Mouse Model through Modulation of Oxidative Stress.Hakimizadeh E, Zamanian M, Giménez-Llort L, Sciorati C, Nikbakhtzadeh M, Kujawska M, Kaeidi A, Hassanshahi J, Fatemi I. Hakimizadeh E, et al. Antioxidants (Basel). 2021 Apr 23;10(5):649. doi: 10.3390/antiox10050649. Antioxidants (Basel). 2021. PMID: 33922431 Free PMC article.
-
- International Diabetes Federation, corp-author. www.diabetesatlas.org Diabetes Atlas. (7th edition) 2015
- Biomarkers / metabolism
- C-Reactive Protein / metabolism
- Calcium Dobesilate / pharmacology
- Calcium Dobesilate / therapeutic use*
- Cell Membrane Permeability / drug effects
- Cell Movement / drug effects
- Cell Proliferation / drug effects
- Chemokine CCL2 / metabolism
- Diabetes Mellitus / drug therapy*
- Diabetes Mellitus / pathology
- Diabetes Mellitus / physiopathology*
- Endothelium, Vascular / drug effects
- Endothelium, Vascular / pathology*
- Endothelium, Vascular / physiopathology*
- Glucose / toxicity
- Human Umbilical Vein Endothelial Cells / drug effects
- Human Umbilical Vein Endothelial Cells / metabolism
- Humans
- Inflammation / pathology*
- Inflammation Mediators / metabolism
- Intercellular Adhesion Molecule-1 / metabolism
- Neoplasm Proteins / genetics
- Neoplasm Proteins / metabolism
- Proteoglycans / genetics
- Proteoglycans / metabolism
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Serum Amyloid P-Component / metabolism
- Time Factors
- Up-Regulation / drug effects
- Vascular Endothelial Growth Factor A / genetics
- Vascular Endothelial Growth Factor A / metabolism
- Vascular Endothelial Growth Factor Receptor-2 / genetics
- Vascular Endothelial Growth Factor Receptor-2 / metabolism
- Biomarkers
- Chemokine CCL2
- ESM1 protein, human
- Inflammation Mediators
- Neoplasm Proteins
- Proteoglycans
- RNA, Messenger
- Serum Amyloid P-Component
- Vascular Endothelial Growth Factor A
- Intercellular Adhesion Molecule-1
- PTX3 protein
- Calcium Dobesilate
- C-Reactive Protein
- Vascular Endothelial Growth Factor Receptor-2
- Glucose
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5779917/bin/MMR-16-06-8635-g02.jpg)
Figure 4.
CaD prevents migration of HUVECs,…
Figure 4.
CaD prevents migration of HUVECs, which partially induced by diabetes or HG. Transwell…
Figure 5.
HG increased the permeability of…
Figure 5.
HG increased the permeability of HUVECs, which inhibited by CaD. Permeability assay analysing…
Figure 6.
HG (35 mmol/l) increased the…
Figure 6.
HG (35 mmol/l) increased the mRNA levels of VEGF, VEGFR-2, endocan in a…
Figure 7.
HG (35 mmol/l) increased the…
Figure 7.
HG (35 mmol/l) increased the protein levels of VEGF, VEGFR-2, endocan in a…
- Investigation of the Mechanism Underlying Calcium Dobesilate-Mediated Improvement of Endothelial Dysfunction and Inflammation Caused by High Glucose.Zhou Y, Qi C, Li S, Shao X, Ni Z. Zhou Y, et al. Mediators Inflamm. 2019 Oct 21;2019:9893682. doi: 10.1155/2019/9893682. eCollection 2019. Mediators Inflamm. 2019. PMID: 31780874 Free PMC article.
- Diabetic Nephropathy Can Be Treated with Calcium Dobesilate by Alleviating the Chronic Inflammatory State and Improving Endothelial Cell Function.Zhou Y, Qi C, Li S, Shao X, Mou S, Ni Z. Zhou Y, et al. Cell Physiol Biochem. 2018;51(3):1119-1133. doi: 10.1159/000495491. Epub 2018 Nov 26. Cell Physiol Biochem. 2018. PMID: 30476916 Clinical Trial.
- ROCK inhibitor fasudil attenuated high glucose-induced MCP-1 and VCAM-1 expression and monocyte-endothelial cell adhesion.Li H, Peng W, Jian W, Li Y, Li Q, Li W, Xu Y. Li H, et al. Cardiovasc Diabetol. 2012 Jun 13;11:65. doi: 10.1186/1475-2840-11-65. Cardiovasc Diabetol. 2012. PMID: 22694757 Free PMC article. Clinical Trial.
- Calcium dobesilate reduces VEGF signaling by interfering with heparan sulfate binding site and protects from vascular complications in diabetic mice.Njau F, Shushakova N, Schenk H, Wulfmeyer VC, Bollin R, Menne J, Haller H. Njau F, et al. PLoS One. 2020 Jan 14;15(1):e0218494. doi: 10.1371/journal.pone.0218494. eCollection 2020. PLoS One. 2020. PMID: 31935212 Free PMC article.
- Calcium Dobesilate and Micro-vascular diseases.Liu J, Li S, Sun D. Liu J, et al. Life Sci. 2019 Mar 15;221:348-353. doi: 10.1016/j.lfs.2019.02.023. Epub 2019 Feb 12. Life Sci. 2019. PMID: 30769115 Review.
- Intravitreal Ranibizumab Alone or in Combination with Calcium Dobesilate for the Treatment of Diabetic Macular Edema in Nonproliferative Diabetic Retinopathy Patients: 12-Month Outcomes of a Retrospective Study.Wang D, Wang H, Wu S, Yang X, Xu J. Wang D, et al. Int J Clin Pract. 2022 Oct 20;2022:6725225. doi: 10.1155/2022/6725225. eCollection 2022. Int J Clin Pract. 2022. PMID: 36340967 Free PMC article. Review.
- An In Vitro Model of Diabetic Retinal Vascular Endothelial Dysfunction and Neuroretinal Degeneration.Wang Q, Zhang X, Wang K, Zhu L, Qiu B, Chen X, Lin X, Nie Y. Wang Q, et al. J Diabetes Res. 2021 Nov 10;2021:9765119. doi: 10.1155/2021/9765119. eCollection 2021. J Diabetes Res. 2021. PMID: 34805414 Free PMC article.
- Effect of Calcium Dobesilate in Preventing Contrast-Induced Nephropathy in Patients with Diabetes and Chronic Kidney Disease.Zhang H, Guo SH, Xue ZK, Zhang YR, Wang JR, Che JJ, Liu T, Tao HY, Li GP, Rha SW, Ashraful-Haque SZ, Chen KY. Zhang H, et al. Clinics (Sao Paulo). 2021 Oct 18;76:e2942. doi: 10.6061/clinics/2021/e2942. eCollection 2021. Clinics (Sao Paulo). 2021. PMID: 34669873 Free PMC article.
- MiR-302a Limits Vascular Inflammation by Suppressing Nuclear Factor-κ B Pathway in Endothelial Cells.Yuan JN, Hong Y, Ma ZL, Pang RP, Lei QQ, Lv XF, Zhou JG, Huang H, Zhang TT. Yuan JN, et al. Front Cell Dev Biol. 2021 Aug 2;9:682574. doi: 10.3389/fcell.2021.682574. eCollection 2021. Front Cell Dev Biol. 2021. PMID: 34409030 Free PMC article.
- Calcium Dobesilate Reverses Cognitive Deficits and Anxiety-Like Behaviors in the D-Galactose-Induced Aging Mouse Model through Modulation of Oxidative Stress.Hakimizadeh E, Zamanian M, Giménez-Llort L, Sciorati C, Nikbakhtzadeh M, Kujawska M, Kaeidi A, Hassanshahi J, Fatemi I. Hakimizadeh E, et al. Antioxidants (Basel). 2021 Apr 23;10(5):649. doi: 10.3390/antiox10050649. Antioxidants (Basel). 2021. PMID: 33922431 Free PMC article.
-
- International Diabetes Federation, corp-author. www.diabetesatlas.org Diabetes Atlas. (7th edition) 2015
- Biomarkers / metabolism
- C-Reactive Protein / metabolism
- Calcium Dobesilate / pharmacology
- Calcium Dobesilate / therapeutic use*
- Cell Membrane Permeability / drug effects
- Cell Movement / drug effects
- Cell Proliferation / drug effects
- Chemokine CCL2 / metabolism
- Diabetes Mellitus / drug therapy*
- Diabetes Mellitus / pathology
- Diabetes Mellitus / physiopathology*
- Endothelium, Vascular / drug effects
- Endothelium, Vascular / pathology*
- Endothelium, Vascular / physiopathology*
- Glucose / toxicity
- Human Umbilical Vein Endothelial Cells / drug effects
- Human Umbilical Vein Endothelial Cells / metabolism
- Humans
- Inflammation / pathology*
- Inflammation Mediators / metabolism
- Intercellular Adhesion Molecule-1 / metabolism
- Neoplasm Proteins / genetics
- Neoplasm Proteins / metabolism
- Proteoglycans / genetics
- Proteoglycans / metabolism
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Serum Amyloid P-Component / metabolism
- Time Factors
- Up-Regulation / drug effects
- Vascular Endothelial Growth Factor A / genetics
- Vascular Endothelial Growth Factor A / metabolism
- Vascular Endothelial Growth Factor Receptor-2 / genetics
- Vascular Endothelial Growth Factor Receptor-2 / metabolism
- Biomarkers
- Chemokine CCL2
- ESM1 protein, human
- Inflammation Mediators
- Neoplasm Proteins
- Proteoglycans
- RNA, Messenger
- Serum Amyloid P-Component
- Vascular Endothelial Growth Factor A
- Intercellular Adhesion Molecule-1
- PTX3 protein
- Calcium Dobesilate
- C-Reactive Protein
- Vascular Endothelial Growth Factor Receptor-2
- Glucose
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
![Figure 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5779917/bin/MMR-16-06-8635-g03.jpg)
![Figure 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5779917/bin/MMR-16-06-8635-g04.jpg)
![Figure 6.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5779917/bin/MMR-16-06-8635-g05.jpg)
Figure 7.
HG (35 mmol/l) increased the…
Figure 7.
HG (35 mmol/l) increased the protein levels of VEGF, VEGFR-2, endocan in a…
![Figure 7.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5779917/bin/MMR-16-06-8635-g06.jpg)
References
- International Diabetes Federation, corp-author. Diabetes Atlas. (7th edition) 2015
- Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, Goldstein-Fuchs J, Hirsch IB, Kalantar-Zadeh K, Narva AS, Navaneethan SD, et al. Diabetic kidney disease: A report from an ADA Consensus Conference. Am J Kidney Dis. 2014;64:510–533. doi: 10.1053/j.ajkd.2014.08.001.
- Fu J, Lee K, Chuang PY, Liu Z, He JC. Glomerular endothelial cell injury and cross talk in diabetic kidney disease. Am J Physiol Renal Physiol. 2015;308:F287–F297. doi: 10.1152/ajprenal.00533.2014.
- Cheng H, Harris RC. Renal endothelial dysfunction in diabetic nephropathy. Cardiovasc Haematol Disord Drug Targets. 2014;14:22–33. doi: 10.2174/1871529X14666140401110841.
- Navarro-González JF, Mora-Fernández C, de Fuentes M Muros, García-Pérez J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol. 2011;7:327–340. doi: 10.1038/nrneph.2011.51.
- Galkina E, Ley K. Leukocyte recruitment and vascular injury in diabetic nephropathy. J Am Soc Nephrol. 2006;17:368–377. doi: 10.1681/ASN.2005080859.
- Sugimoto H, Shikata K, Hirata K, Akiyama K, Matsuda M, Kushiro M, Shikata Y, Miyatake N, Miyasaka M, Makino H. Increased expression of intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli: Glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation. Diabetes. 1997;46:2075–2081. doi: 10.2337/diab.46.12.2075.
- Seron D, Cameron JS, Haskard DO. Expression of VCAM-1 in the normal and diseased kidney. Nephrol Dial Transplant. 1991;6:917–922. doi: 10.1093/ndt/6.12.917.
- Tejerina T, Ruiz E. Calcium dobesilate: Pharmacology and future approaches. Gen Pharmacol. 1998;31:357–360. doi: 10.1016/S0306-3623(98)00040-8.
- Javadzadeh A, Ghorbanihaghjo A, Adl FH, Andalib D, Khojasteh-Jafari H, Ghabili K. Calcium dobesilate reduces endothelin-1 and high-sensitivity C-reactive protein serum levels in patients with diabetic retinopathy. Mol Vis. 2013;19:62–68.
- Rabe E, Jaeger KA, Bulitta M, Pannier F. Calcium dobesilate in patients suffering from chronic venous insufficiency: A double-blind, placebo-controlled, clinical trial. Phlebology. 2011;26:162–168. doi: 10.1258/phleb.2010.010051.
- Hall JF. Modern management of hemorrhoidal disease. Gastroenterol Clin North Am. 2013;42:759–772. doi: 10.1016/j.gtc.2013.09.001.
- Zhang X. Therapeutic effects of calcium dobesilate on diabetic nephropathy mediated through reduction of expression of PAI-1. Exp Ther Med. 2013;5:295–299. doi: 10.3892/etm.2012.755.
- Jafarey M, Ashtiyani S Changizi, Najafi H. Calcium dobesilate for prevention of gentamicin-induced nephrotoxicity in rats. Iran J Kidney Dis. 2014;8:46–52.
- Pan SL, Guh JH, Huang YW, Chern JW, Chou JY, Teng CM. Identification of apoptotic and antiangiogenic activities of terazosin in human prostate cancer and endothelial cells. J Urol. 2003;169:724–729. doi: 10.1097/00005392-200302000-00074.
- Irwin DC, van Patot MC Tissot, Tucker A, Bowen R. Direct ANP inhibition of hypoxia-induced inflammatory pathways in pulmonary microvascular and macrovascular endothelial monolayers. Am J Physiol Lung Cell Mol Physiol. 2005;288:L849–L859. doi: 10.1152/ajplung.00294.2004.
- Demirtas S, Caliskan A, Guclu O, Yazici S, Karahan O, Yavuz C, Mavitas B. Can calcium dobesilate be used safely for peripheral microvasculopathies that require neoangiogenesis? Med Sci Monit Basic Res. 2013;19:253–257. doi: 10.12659/MSMBR.889427.
- Zhang X, Liu W, Wu S, Jin J, Li W, Wang N. Calcium dobesilate for diabetic retinopathy: A systematic review and meta-analysis. Sci China Life Sci. 2015;58:101–107. doi: 10.1007/s11427-014-4792-1.
- Krakoff J, Lindsay RS, Looker HC, Nelson RG, Hanson RL, Knowler WC. Incidence of retinopathy and nephropathy in youth-onset compared with adult-onset type 2 diabetes. Diabetes Care. 2003;26:76–81. doi: 10.2337/diacare.26.1.76.
- Seyer-Hansen K. Renal hypertrophy in experimental diabetes mellitus. Kidney Int. 1983;23:643–646. doi: 10.1038/ki.1983.71.
- Seyer-Hansen K. Renal hypertrophy in streptozotocin-diabetic rats. Clin Sci Mol Med. 1976;51:551–555.
- Nyengaard JR, Rasch R. The impact of experimental diabetes mellitus in rats on glomerular capillary number and sizes. Diabetologia. 1993;36:189–194. doi: 10.1007/BF00399948.
- Osterby R, Nyberg G. New vessel formation in the renal corpuscles in advanced diabetic glomerulopathy. J Diabet Complications. 1987;1:122–127. doi: 10.1016/S0891-6632(87)80069-7.
- Wehner H, Nelischer G. Morphometric investigations on intrarenal vessels of streptozotocin-diabetic rats. Virchows Arch A Pathol Anat Histopathol. 1991;419:231–235. doi: 10.1007/BF01626353.
- Nakagawa T, Kosugi T, Haneda M, Rivard CJ, Long DA. Abnormal angiogenesis in diabetic nephropathy. Diabetes. 2009;58:1471–1478. doi: 10.2337/db09-0119.
- Kanesaki Y, Suzuki D, Uehara G, Toyoda M, Katoh T, Sakai H, Watanabe T. Vascular endothelial growth factor gene expression is correlated with glomerular neovascularization in human diabetic nephropathy. Am J Kidney Dis. 2005;45:288–294. doi: 10.1053/j.ajkd.2004.09.020.
- Min W, Yamanaka N. Three-dimensional analysis of increased vasculature around the glomerular vascular pole in diabetic nephropathy. Virchows Arch A Pathol Anat Histopathol. 1993;423:201–207. doi: 10.1007/BF01614771.
- Yuan J, Fang W, Lin A, Ni Z, Qian J. Angiopoietin-2/Tie2 signaling involved in TNF-α induced peritoneal angiogenesis. Int J Artif Organs. 2012;35:655–662.
- Cooper ME, Vranes D, Youssef S, Stacker SA, Cox AJ, Rizkalla B, Casley DJ, Bach LA, Kelly DJ, Gilbert RE. Increased renal expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in experimental diabetes. Diabetes. 1999;48:2229–2239. doi: 10.2337/diabetes.48.11.2229.
- Hohenstein B, Hausknecht B, Boehmer K, Riess R, Brekken RA, Hugo CP. Local VEGF activity but not VEGF expression is tightly regulated during diabetic nephropathy in man. Kidney Int. 2006;69:1654–1661. doi: 10.1038/sj.ki.5000294.
- Baelde HJ, Eikmans M, Doran PP, Lappin DW, de Heer E, Bruijn JA. Gene expression profiling in glomeruli from human kidneys with diabetic nephropathy. Am J Kidney Dis. 2004;43:636–650. doi: 10.1053/j.ajkd.2003.12.028.
- Baelde HJ, Eikmans M, Lappin DW, Doran PP, Hohenadel D, Brinkkoetter PT, Van der Woude FJ, Waldherr R, Rabelink TJ, de Heer E, Bruijn JA. Reduction of VEGF-A and CTGF expression in diabetic nephropathy is associated with podocyte loss. Kidney Int. 2007;71:637–645. doi: 10.1038/sj.ki.5002101.
- Lindenmeyer MT, Kretzler M, Boucherot A, Berra S, Yasuda Y, Henger A, Eichinger F, Gaiser S, Schmid H, Rastaldi MP, et al. Interstitial vascular rarefaction and reduced VEGF-A expression in human diabetic nephropathy. J Am Soc Nephrol. 2007;18:1765–1776. doi: 10.1681/ASN.2006121304.
- García-García PM, Getino-Melián MA, Domínguez-Pimentel V, Navarro-González JF. Inflammation in diabetic kidney disease. World J Diabetes. 2014;5:431–443. doi: 10.4239/wjd.v5.i4.431.
- Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care. 2004;27:813–823. doi: 10.2337/diacare.27.3.813.
- Navarro JF, Milena FJ, Mora C, León C, García J. Renal pro-inflammatory cytokine gene expression in diabetic nephropathy: Effect of angiotensin-converting enzyme inhibition and pentoxifylline administration. Am J Nephrol. 2006;26:562–570. doi: 10.1159/000098004.
- Sekizuka K, Tomino Y, Sei C, Kurusu A, Tashiro K, Yamaguchi Y, Kodera S, Hishiki T, Shirato I, Koide H. Detection of serum IL-6 in patients with diabetic nephropathy. Nephron. 1994;68:284–285. doi: 10.1159/000188281.
- Moriwaki Y, Yamamoto T, Shibutani Y, Aoki E, Tsutsumi Z, Takahashi S, Okamura H, Koga M, Fukuchi M, Hada T. Elevated levels of interleukin-18 and tumor necrosis factor-alpha in serum of patients with type 2 diabetes mellitus: Relationship with diabetic nephropathy. Metabolism. 2003;52:605–608. doi: 10.1053/meta.2003.50096.
- Navarro JF, Mora C, Muros M, García J. Urinary tumour necrosis factor-alpha excretion independently correlates with clinical markers of glomerular and tubulointerstitial injury in type 2 diabetic patients. Nephrol Dial Transplant. 2006;21:3428–3434. doi: 10.1093/ndt/gfl469.
- Royall JA, Berkow RL, Beckman JS, Cunningham MK, Matalon S, Freeman BA. Tumor necrosis factor and interleukin 1 alpha increase vascular endothelial permeability. Am J Physiol. 1989;257:L399–L410.
- Navarro-González JF, Mora-Fernández C. The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol. 2008;19:433–442. doi: 10.1681/ASN.2007091048.
- Vestra M Dalla, Mussap M, Gallina P, Bruseghin M, Cernigoi AM, Saller A, Plebani M, Fioretto P. Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes. J Am Soc Nephrol. 2005;16(Suppl 1):S78–S82. doi: 10.1681/ASN.2004110961.
- Ruef C, Budde K, Lacy J, Northemann W, Baumann M, Sterzel RB, Coleman DL. Interleukin 6 is an autocrine growth factor for mesangial cells. Kidney Int. 1990;38:249–257. doi: 10.1038/ki.1990.193.
- Mariño E, Cardier JE. Differential effect of IL-18 on endothelial cell apoptosis mediated by TNF-alpha and Fas (CD95) Cytokine. 2003;22:142–148. doi: 10.1016/S1043-4666(03)00150-9.
- Stuyt RJ, Netea MG, Geijtenbeek TB, Kullberg BJ, Dinarello CA, van der Meer JW. Selective regulation of intercellular adhesion molecule-1 expression by interleukin-18 and interleukin-12 on human monocytes. Immunology. 2003;110:329–334. doi: 10.1046/j.1365-2567.2003.01747.x.
- Bertani T, Abbate M, Zoja C, Corna D, Perico N, Ghezzi P, Remuzzi G. Tumor necrosis factor induces glomerular damage in the rabbit. Am J Pathol. 1989;134:419–430.
- DiPetrillo K, Coutermarsh B, Gesek FA. Urinary tumor necrosis factor contributes to sodium retention and renal hypertrophy during diabetes. Am J Physiol Renal Physiol. 2003;284:F113–F121. doi: 10.1152/ajprenal.00026.2002.
- Dipetrillo K, Gesek FA. Pentoxifylline ameliorates renal tumor necrosis factor expression, sodium retention, and renal hypertrophy in diabetic rats. Am J Nephrol. 2004;24:352–359. doi: 10.1159/000079121.
Source: PubMed