Состояние системы ангиогенеза как отражение эндотелиальной дисфункции у пациентов с сахарным диабетом 2-го типа: взаимосвязь с ожирением - Журнал Терапевтический архив №10 Вопросы эндокринологии 2020
Состояние системы ангиогенеза как отражение эндотелиальной дисфункции у пациентов с сахарным диабетом 2-го типа: взаимосвязь с ожирением
Северина А.С., Шестакова М.В. Состояние системы ангиогенеза как отражение эндотелиальной дисфункции у пациентов с сахарным диабетом 2-го типа: взаимосвязь с ожирением. Терапевтический архив. 2020; 92 (10): 23–28.
DOI: 10.26442/00403660.2020.10.000781
DOI: 10.26442/00403660.2020.10.000781
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Аннотация
Цель. Оценить состояние системы ангиогенеза у пациентов с сахарным диабетом 2-го типа (СД 2) и его взаимосвязь с наличием ожирения.
Материалы и методы. В исследование включены 104 пациента с СД 2. Пациенты распределены на две группы: группа пациентов с ожирением (индекс массы тела ≥30 кг/м2; n=63) и пациенты без ожирения (индекс массы тела <30 кг/м2; n=41). Всем пациентам проводили клинико-лабораторное обследование, а также оценили уровни экспрессии матричной РНК (мРНК) сосудистого эндотелиального фактора роста (VEGF) и двух его рецепторов flt-1 (fms-like tyrosine kinase 1), KDR (human kinase insert domain receptor) в мононуклеарных клетках крови.
Результаты. При сравнении показателей системы ангиогенеза в исследуемых группах нами не обнаружено статистически значимых различий. Обращает на себя внимание несколько более низкий уровень экспрессии мРНК VEGF у мужчин по сравнению с женщинами: 0,19 (0,14; 0,32) и 0,28 (0,12; 0,4) соответственно, р=0,2236, а также статистически значимо более низкий уровень экспрессии мРНК рецептора flt-1: 0,14 (0,04; 0,3) и 0,25 (0,12; 0,38), р=0,0321. При оценке корреляций нами обнаружены статистически значимые корреляции уровня экспрессии мРНК VEGF с уровнем мРНК рецепторов, как flt-1, так и KDR, а также корреляция уровней экспрессии мРНК рецепторов друг с другом. Также обнаружены сильные положительные корреляции уровня экспрессии мРНК VEGF, flt-1, KDR и его рецепторов с индексом массы тела (r=0,86107, r=0,86125, r=0,86112 соответственно, p<0,001).
Заключение. Полученные нами результаты позволяют говорить о наличии закономерной связи системы ангиогенеза и ожирения. Дальнейшее изучение данного вопроса представляется перспективным с позиции поиска новой терапевтической стратегии борьбы с ожирением и, как следствие, его осложнениями.
Ключевые слова: сахарный диабет 2-го типа, ожирение, ангиогенез, сосудистый эндотелиальный фактор роста, рецептор flt-1, рецептор KDR.
Materials and methods. 104 patients with diabetes mellitus type 2 were included in the study. Patients were divided in 2 groups: Obesity+ (body mass index ≥30 kg/m2; n=63) and Obesity- (body mass index <30 kg/m2; n=41). In all patients was performed clinico-diagnostical examination. mRNA expression levels of vascular endothelial growth factor (VEGF), its receptors flt-1 (fms-like tyrosine kinase 1), KDR (human kinase insert domain receptor) were determined in blood mononuclear cells.
Results. There were no statistically significant differences in investigated parameters between study groups. mRNA expression level of VEGF was slightly lower in men compared to women: 0.19 (0.14; 0.32) vs 0.28 (0.12; 0.4) respectively, р=0.2236. MRNA expression level of flt-1 was lower in men compared to women: 0.14 (0.04; 0.3) vs 0.25 (0.12; 0.38), р=0.0321 (statistically significant). We found statistically significant correlations of mRNA expression level of VEGF with mRNA expression level of flt-1 and KDR. Also we found strong positive correlations of BMI and mRNA expression levels VEGF, flt-1, KDR (r=0.86107, r=0.86125, r=0.86112, respectively, p<0.001).
Conclusion. Results of the study displayed relationship of obesity and angiogenesis system condition in patients with diabetes mellitus type 2. Further investigations are perspective for the future as a way to new therapeutical approach of obesity and its complications treatment.
Keywords: diabetes mellitus type 2, obesity, angiogenesis, vascular endothelial growth factor, fms-like tyrosine kinase 1, human kinase insert domain receptor.
Материалы и методы. В исследование включены 104 пациента с СД 2. Пациенты распределены на две группы: группа пациентов с ожирением (индекс массы тела ≥30 кг/м2; n=63) и пациенты без ожирения (индекс массы тела <30 кг/м2; n=41). Всем пациентам проводили клинико-лабораторное обследование, а также оценили уровни экспрессии матричной РНК (мРНК) сосудистого эндотелиального фактора роста (VEGF) и двух его рецепторов flt-1 (fms-like tyrosine kinase 1), KDR (human kinase insert domain receptor) в мононуклеарных клетках крови.
Результаты. При сравнении показателей системы ангиогенеза в исследуемых группах нами не обнаружено статистически значимых различий. Обращает на себя внимание несколько более низкий уровень экспрессии мРНК VEGF у мужчин по сравнению с женщинами: 0,19 (0,14; 0,32) и 0,28 (0,12; 0,4) соответственно, р=0,2236, а также статистически значимо более низкий уровень экспрессии мРНК рецептора flt-1: 0,14 (0,04; 0,3) и 0,25 (0,12; 0,38), р=0,0321. При оценке корреляций нами обнаружены статистически значимые корреляции уровня экспрессии мРНК VEGF с уровнем мРНК рецепторов, как flt-1, так и KDR, а также корреляция уровней экспрессии мРНК рецепторов друг с другом. Также обнаружены сильные положительные корреляции уровня экспрессии мРНК VEGF, flt-1, KDR и его рецепторов с индексом массы тела (r=0,86107, r=0,86125, r=0,86112 соответственно, p<0,001).
Заключение. Полученные нами результаты позволяют говорить о наличии закономерной связи системы ангиогенеза и ожирения. Дальнейшее изучение данного вопроса представляется перспективным с позиции поиска новой терапевтической стратегии борьбы с ожирением и, как следствие, его осложнениями.
Ключевые слова: сахарный диабет 2-го типа, ожирение, ангиогенез, сосудистый эндотелиальный фактор роста, рецептор flt-1, рецептор KDR.
________________________________________________
Materials and methods. 104 patients with diabetes mellitus type 2 were included in the study. Patients were divided in 2 groups: Obesity+ (body mass index ≥30 kg/m2; n=63) and Obesity- (body mass index <30 kg/m2; n=41). In all patients was performed clinico-diagnostical examination. mRNA expression levels of vascular endothelial growth factor (VEGF), its receptors flt-1 (fms-like tyrosine kinase 1), KDR (human kinase insert domain receptor) were determined in blood mononuclear cells.
Results. There were no statistically significant differences in investigated parameters between study groups. mRNA expression level of VEGF was slightly lower in men compared to women: 0.19 (0.14; 0.32) vs 0.28 (0.12; 0.4) respectively, р=0.2236. MRNA expression level of flt-1 was lower in men compared to women: 0.14 (0.04; 0.3) vs 0.25 (0.12; 0.38), р=0.0321 (statistically significant). We found statistically significant correlations of mRNA expression level of VEGF with mRNA expression level of flt-1 and KDR. Also we found strong positive correlations of BMI and mRNA expression levels VEGF, flt-1, KDR (r=0.86107, r=0.86125, r=0.86112, respectively, p<0.001).
Conclusion. Results of the study displayed relationship of obesity and angiogenesis system condition in patients with diabetes mellitus type 2. Further investigations are perspective for the future as a way to new therapeutical approach of obesity and its complications treatment.
Keywords: diabetes mellitus type 2, obesity, angiogenesis, vascular endothelial growth factor, fms-like tyrosine kinase 1, human kinase insert domain receptor.
Список литературы
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3. Wang H, Wang Q, Venugopal J, et al. Obesity-induced Endothelial Dysfunction is Prevented by Neutrophil Extracellular Trap Inhibition. Sci Rep. 2018;8(1). doi: 10.1038/s41598-018-23256-y
4. Kaur R, Kaur M, Singh J. Endothelial Dysfunction and Platelet Hyperactivity in Type 2 Diabetes Mellitus: Molecular Insights and Therapeutic Strategies. Cardiovasc Diabetol. 2018;17(1):121. doi: 10.1186/s12933-018-0763-3
5. Cheng R, Ma J-X. Angiogenesis in Diabetes and Obesity. Rev Endocr Metab Disord. 2015;16(1):67-75. doi: 10.1007/s11154-015-9310-7
6. Sung H-K, Doh K-O, Son JE, et al. Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis. Cell Metabolism. 2013;17(1):61-72. doi: 10.1016/j.cmet.2012.12.010
7. O’Rourke RW, White AE, Metcalf MD, et al. Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells. Diabetologia. 2011;54(6): 1480-90. doi: 10.1007/s00125-011-2103-y
8. Boyum A. Isolation of Mononuclear Cells and Granulocytes From Human Blood. Isolation of Monuclear Cells by One Centrifugation, and of Granulocytes by Combining Centrifugation and Sedimentation at 1 G Scan. J Clin Lab Invest. 1968;21(Suppl. 97):77-89.
9. Chomszynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162:156-9.
10. Muniyappa R, Iantorno M, Quon MJ. An integrated view of insulin resistance and endothelial dysfunction. Endocrinol Metab Clin North Am. 2008;37:685-711. doi: 10.1016/j.ecl.2008.06.001
11. Holmes DIR, Zachary I. The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease. Genome Biol. 2005;6:209. doi: 10.1186/gb-2005-6-2-209
12. Lijnen HR. Angiogenesis and obesity. Cardiovasc Res. 2008;78(2):286-93. doi: 10.1093/cvr/cvm007
13. Zafar MI, Mills K, Ye X, et al. Association between the expression of vascular endothelial growth factors and metabolic syndrome or its components: a systematic review and meta-analysis. Diabetol Metab Syndr. 2018;10(1). doi: 10.1186/s13098-018-0363-0
14. Miyazawa-Hoshimoto S, Takahashi K, Bujo H, et al. Elevated serum vascular endothelial growth factor is associated with visceral fat accumulation in human obese subjects. Diabetologia. 2003;46(11):1483-8. doi: 10.1007/s00125-003-1221-6
15. Silha JV, Krsek M, Sucharda P, Murphy LJ. Angiogenic factors are elevated in overweight and obese individuals. Int J Obes. 2005;29(11):1308-14. doi: 10.1038/sj.ijo.0802987
16. Sandhofer A, Tatarczyk T, Kirchmair R, et al. Are plasma VEGF and its soluble receptor sFlt-1 atherogenic risk factors? Cross-sectional data from the SAPHIR study. Atherosclerosis. 2009;206(1):265-9. doi: 10.1016/j.atherosclerosis.2009.01.031
17. Wada H, Ura S, Kitaoka S, et al. Distinct Characteristics of Circulating Vascular Endothelial Growth Factor-A and C Levels in Human Subjects. PLoS ONE. 2011;6(12):e29351. doi: 10.1371/journal.pone.0029351
18. Loebig M, Klement J, Schmoller A, et al. Evidence for a Relationship between VEGF and BMI Independent of Insulin Sensitivity by Glucose Clamp Procedure in a Homogenous Group Healthy Young Men. PLoS ONE. 2010;5(9):e12610. doi: 10.1371/journal.pone.0012610
19. Wieczór R, Wieczór AM, Gadomska G, et al. Overweight and obesity versus concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 in plasma of patients with lower limb chronic ischemia. J Zhejiang Univ Sci. 2016;17(11):842-9. doi: 10.1631/jzus.b1600009
20. Hong KH, Ryu J, Han KH. Monocyte chemoattractant protein-1–induced angiogenesis is mediated by vascular endothelial growth factor-A. Blood. 2005;105(4):1405-7. doi: 10.1182/blood-2004-08-3178
21. Lee CC, Hsieh MF, et al. Clinical association of circulating VEGF-B levels with hyperlipidemia and target organ damage in type 2 diabetic patients. J Biol Regul Homeost Agents. 2014;28:225-36
22. Elias I, Franckhauser S, Bosch F. Response to Comment on: Elias, et al. Adipose Tissue Overexpression of Vascular Endothelial Growth Factor Protects Against Diet-Induced Obesity and Insulin Resistance. Diabetes. 2012;61:1801-13. doi: 10.2337/db12-1274
23. Wiewiora M, Mertas A, Gluck M, et al. Effect of Weight Loss Surgery on Biomarkers of Angiogenesis in Obese Patients. Obes Surg. 2020. doi: 10.1007/s11695-020-04580-7
24. Sung H-K, Doh K-O, Son JE, et al. Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis. Cell Metab. 2013;17(1):61-72. doi: 10.1016/j.cmet.2012.
12.010
25. Robciuc MR, Kivelä R, Williams IM, et al. VEGFB/VEGFR1-Induced Expansion of Adipose Vasculature Counteracts Obesity and Related Metabolic Complications. Cell Metab. 2016;23(4):712-24. doi: 10.1016/j.cmet.2016.03.004
26. Bry M, Kivelä R, Holopainen T, et al. Vascular Endothelial Growth Factor-B Acts as a Coronary Growth Factor in Transgenic Rats Without Inducing Angiogenesis, Vascular Leak, or Inflammation. Circulation. 2010;122(17):1725-33. doi: 10.1161/circulationaha.110.957332
2. Samad F, Ruf W. Inflammation, obesity, and thrombosis. Blood. 2013;122(20): 3415-22. doi: 10.1182/blood-2013-05-427708
3. Wang H, Wang Q, Venugopal J, et al. Obesity-induced Endothelial Dysfunction is Prevented by Neutrophil Extracellular Trap Inhibition. Sci Rep. 2018;8(1). doi: 10.1038/s41598-018-23256-y
4. Kaur R, Kaur M, Singh J. Endothelial Dysfunction and Platelet Hyperactivity in Type 2 Diabetes Mellitus: Molecular Insights and Therapeutic Strategies. Cardiovasc Diabetol. 2018;17(1):121. doi: 10.1186/s12933-018-0763-3
5. Cheng R, Ma J-X. Angiogenesis in Diabetes and Obesity. Rev Endocr Metab Disord. 2015;16(1):67-75. doi: 10.1007/s11154-015-9310-7
6. Sung H-K, Doh K-O, Son JE, et al. Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis. Cell Metabolism. 2013;17(1):61-72. doi: 10.1016/j.cmet.2012.12.010
7. O’Rourke RW, White AE, Metcalf MD, et al. Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells. Diabetologia. 2011;54(6): 1480-90. doi: 10.1007/s00125-011-2103-y
8. Boyum A. Isolation of Mononuclear Cells and Granulocytes From Human Blood. Isolation of Monuclear Cells by One Centrifugation, and of Granulocytes by Combining Centrifugation and Sedimentation at 1 G Scan. J Clin Lab Invest. 1968;21(Suppl. 97):77-89.
9. Chomszynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162:156-9.
10. Muniyappa R, Iantorno M, Quon MJ. An integrated view of insulin resistance and endothelial dysfunction. Endocrinol Metab Clin North Am. 2008;37:685-711. doi: 10.1016/j.ecl.2008.06.001
11. Holmes DIR, Zachary I. The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease. Genome Biol. 2005;6:209. doi: 10.1186/gb-2005-6-2-209
12. Lijnen HR. Angiogenesis and obesity. Cardiovasc Res. 2008;78(2):286-93. doi: 10.1093/cvr/cvm007
13. Zafar MI, Mills K, Ye X, et al. Association between the expression of vascular endothelial growth factors and metabolic syndrome or its components: a systematic review and meta-analysis. Diabetol Metab Syndr. 2018;10(1). doi: 10.1186/s13098-018-0363-0
14. Miyazawa-Hoshimoto S, Takahashi K, Bujo H, et al. Elevated serum vascular endothelial growth factor is associated with visceral fat accumulation in human obese subjects. Diabetologia. 2003;46(11):1483-8. doi: 10.1007/s00125-003-1221-6
15. Silha JV, Krsek M, Sucharda P, Murphy LJ. Angiogenic factors are elevated in overweight and obese individuals. Int J Obes. 2005;29(11):1308-14. doi: 10.1038/sj.ijo.0802987
16. Sandhofer A, Tatarczyk T, Kirchmair R, et al. Are plasma VEGF and its soluble receptor sFlt-1 atherogenic risk factors? Cross-sectional data from the SAPHIR study. Atherosclerosis. 2009;206(1):265-9. doi: 10.1016/j.atherosclerosis.2009.01.031
17. Wada H, Ura S, Kitaoka S, et al. Distinct Characteristics of Circulating Vascular Endothelial Growth Factor-A and C Levels in Human Subjects. PLoS ONE. 2011;6(12):e29351. doi: 10.1371/journal.pone.0029351
18. Loebig M, Klement J, Schmoller A, et al. Evidence for a Relationship between VEGF and BMI Independent of Insulin Sensitivity by Glucose Clamp Procedure in a Homogenous Group Healthy Young Men. PLoS ONE. 2010;5(9):e12610. doi: 10.1371/journal.pone.0012610
19. Wieczór R, Wieczór AM, Gadomska G, et al. Overweight and obesity versus concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 in plasma of patients with lower limb chronic ischemia. J Zhejiang Univ Sci. 2016;17(11):842-9. doi: 10.1631/jzus.b1600009
20. Hong KH, Ryu J, Han KH. Monocyte chemoattractant protein-1–induced angiogenesis is mediated by vascular endothelial growth factor-A. Blood. 2005;105(4):1405-7. doi: 10.1182/blood-2004-08-3178
21. Lee CC, Hsieh MF, et al. Clinical association of circulating VEGF-B levels with hyperlipidemia and target organ damage in type 2 diabetic patients. J Biol Regul Homeost Agents. 2014;28:225-36
22. Elias I, Franckhauser S, Bosch F. Response to Comment on: Elias, et al. Adipose Tissue Overexpression of Vascular Endothelial Growth Factor Protects Against Diet-Induced Obesity and Insulin Resistance. Diabetes. 2012;61:1801-13. doi: 10.2337/db12-1274
23. Wiewiora M, Mertas A, Gluck M, et al. Effect of Weight Loss Surgery on Biomarkers of Angiogenesis in Obese Patients. Obes Surg. 2020. doi: 10.1007/s11695-020-04580-7
24. Sung H-K, Doh K-O, Son JE, et al. Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis. Cell Metab. 2013;17(1):61-72. doi: 10.1016/j.cmet.2012.
12.010
25. Robciuc MR, Kivelä R, Williams IM, et al. VEGFB/VEGFR1-Induced Expansion of Adipose Vasculature Counteracts Obesity and Related Metabolic Complications. Cell Metab. 2016;23(4):712-24. doi: 10.1016/j.cmet.2016.03.004
26. Bry M, Kivelä R, Holopainen T, et al. Vascular Endothelial Growth Factor-B Acts as a Coronary Growth Factor in Transgenic Rats Without Inducing Angiogenesis, Vascular Leak, or Inflammation. Circulation. 2010;122(17):1725-33. doi: 10.1161/circulationaha.110.957332
2. Samad F, Ruf W. Inflammation, obesity, and thrombosis. Blood. 2013;122(20): 3415-22. doi: 10.1182/blood-2013-05-427708
3. Wang H, Wang Q, Venugopal J, et al. Obesity-induced Endothelial Dysfunction is Prevented by Neutrophil Extracellular Trap Inhibition. Sci Rep. 2018;8(1). doi: 10.1038/s41598-018-23256-y
4. Kaur R, Kaur M, Singh J. Endothelial Dysfunction and Platelet Hyperactivity in Type 2 Diabetes Mellitus: Molecular Insights and Therapeutic Strategies. Cardiovasc Diabetol. 2018;17(1):121. doi: 10.1186/s12933-018-0763-3
5. Cheng R, Ma J-X. Angiogenesis in Diabetes and Obesity. Rev Endocr Metab Disord. 2015;16(1):67-75. doi: 10.1007/s11154-015-9310-7
6. Sung H-K, Doh K-O, Son JE, et al. Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis. Cell Metabolism. 2013;17(1):61-72. doi: 10.1016/j.cmet.2012.12.010
7. O’Rourke RW, White AE, Metcalf MD, et al. Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells. Diabetologia. 2011;54(6): 1480-90. doi: 10.1007/s00125-011-2103-y
8. Boyum A. Isolation of Mononuclear Cells and Granulocytes From Human Blood. Isolation of Monuclear Cells by One Centrifugation, and of Granulocytes by Combining Centrifugation and Sedimentation at 1 G Scan. J Clin Lab Invest. 1968;21(Suppl. 97):77-89.
9. Chomszynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162:156-9.
10. Muniyappa R, Iantorno M, Quon MJ. An integrated view of insulin resistance and endothelial dysfunction. Endocrinol Metab Clin North Am. 2008;37:685-711. doi: 10.1016/j.ecl.2008.06.001
11. Holmes DIR, Zachary I. The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease. Genome Biol. 2005;6:209. doi: 10.1186/gb-2005-6-2-209
12. Lijnen HR. Angiogenesis and obesity. Cardiovasc Res. 2008;78(2):286-93. doi: 10.1093/cvr/cvm007
13. Zafar MI, Mills K, Ye X, et al. Association between the expression of vascular endothelial growth factors and metabolic syndrome or its components: a systematic review and meta-analysis. Diabetol Metab Syndr. 2018;10(1). doi: 10.1186/s13098-018-0363-0
14. Miyazawa-Hoshimoto S, Takahashi K, Bujo H, et al. Elevated serum vascular endothelial growth factor is associated with visceral fat accumulation in human obese subjects. Diabetologia. 2003;46(11):1483-8. doi: 10.1007/s00125-003-1221-6
15. Silha JV, Krsek M, Sucharda P, Murphy LJ. Angiogenic factors are elevated in overweight and obese individuals. Int J Obes. 2005;29(11):1308-14. doi: 10.1038/sj.ijo.0802987
16. Sandhofer A, Tatarczyk T, Kirchmair R, et al. Are plasma VEGF and its soluble receptor sFlt-1 atherogenic risk factors? Cross-sectional data from the SAPHIR study. Atherosclerosis. 2009;206(1):265-9. doi: 10.1016/j.atherosclerosis.2009.01.031
17. Wada H, Ura S, Kitaoka S, et al. Distinct Characteristics of Circulating Vascular Endothelial Growth Factor-A and C Levels in Human Subjects. PLoS ONE. 2011;6(12):e29351. doi: 10.1371/journal.pone.0029351
18. Loebig M, Klement J, Schmoller A, et al. Evidence for a Relationship between VEGF and BMI Independent of Insulin Sensitivity by Glucose Clamp Procedure in a Homogenous Group Healthy Young Men. PLoS ONE. 2010;5(9):e12610. doi: 10.1371/journal.pone.0012610
19. Wieczór R, Wieczór AM, Gadomska G, et al. Overweight and obesity versus concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 in plasma of patients with lower limb chronic ischemia. J Zhejiang Univ Sci. 2016;17(11):842-9. doi: 10.1631/jzus.b1600009
20. Hong KH, Ryu J, Han KH. Monocyte chemoattractant protein-1–induced angiogenesis is mediated by vascular endothelial growth factor-A. Blood. 2005;105(4):1405-7. doi: 10.1182/blood-2004-08-3178
21. Lee CC, Hsieh MF, et al. Clinical association of circulating VEGF-B levels with hyperlipidemia and target organ damage in type 2 diabetic patients. J Biol Regul Homeost Agents. 2014;28:225-36
22. Elias I, Franckhauser S, Bosch F. Response to Comment on: Elias, et al. Adipose Tissue Overexpression of Vascular Endothelial Growth Factor Protects Against Diet-Induced Obesity and Insulin Resistance. Diabetes. 2012;61:1801-13. doi: 10.2337/db12-1274
23. Wiewiora M, Mertas A, Gluck M, et al. Effect of Weight Loss Surgery on Biomarkers of Angiogenesis in Obese Patients. Obes Surg. 2020. doi: 10.1007/s11695-020-04580-7
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23. Wiewiora M, Mertas A, Gluck M, et al. Effect of Weight Loss Surgery on Biomarkers of Angiogenesis in Obese Patients. Obes Surg. 2020. doi: 10.1007/s11695-020-04580-7
24. Sung H-K, Doh K-O, Son JE, et al. Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis. Cell Metab. 2013;17(1):61-72. doi: 10.1016/j.cmet.2012.
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26. Bry M, Kivelä R, Holopainen T, et al. Vascular Endothelial Growth Factor-B Acts as a Coronary Growth Factor in Transgenic Rats Without Inducing Angiogenesis, Vascular Leak, or Inflammation. Circulation. 2010;122(17):1725-33. doi: 10.1161/circulationaha.110.957332
Авторы
А.С. Северина, М.В. Шестакова
ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия
Endocrinology Research Centre, Moscow, Russia
ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия
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Endocrinology Research Centre, Moscow, Russia
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