Distinct characteristics of circulating vascular endothelial growth factor-a and C levels in human subjects.
The mechanisms that lead from obesity to atherosclerotic disease are not fully understood. Obesity involves angiogenesis in which vascular endothelial growth factor-A (VEGF-A) plays a key role. On the other hand, vascular endothelial growth factor-C (VEGF-C) plays a pivotal role in lymphangiogenesis...
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2011
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oai:doaj.org-article:76bf549c3929436993e223b0ecd1c5492021-11-18T07:31:48ZDistinct characteristics of circulating vascular endothelial growth factor-a and C levels in human subjects.1932-620310.1371/journal.pone.0029351https://doaj.org/article/76bf549c3929436993e223b0ecd1c5492011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22206010/?tool=EBIhttps://doaj.org/toc/1932-6203The mechanisms that lead from obesity to atherosclerotic disease are not fully understood. Obesity involves angiogenesis in which vascular endothelial growth factor-A (VEGF-A) plays a key role. On the other hand, vascular endothelial growth factor-C (VEGF-C) plays a pivotal role in lymphangiogenesis. Circulating levels of VEGF-A and VEGF-C are elevated in sera from obese subjects. However, relationships of VEGF-C with atherosclerotic risk factors and atherosclerosis are unknown. We determined circulating levels of VEGF-A and VEGF-C in 423 consecutive subjects not receiving any drugs at the Health Evaluation Center. After adjusting for age and gender, VEGF-A levels were significantly and more strongly correlated with the body mass index (BMI) and waist circumference than VEGF-C. Conversely, VEGF-C levels were significantly and more closely correlated with metabolic (e.g., fasting plasma glucose, hemoglobin A1c, immunoreactive insulin, and the homeostasis model assessment of insulin resistance) and lipid parameters (e.g., triglycerides, total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and non-high-density-lipoprotein cholesterol (non-HDL-C)) than VEGF-A. Stepwise regression analyses revealed that independent determinants of VEGF-A were the BMI and age, whereas strong independent determinants of VEGF-C were age, triglycerides, and non-HDL-C. In apolipoprotein E-deficient mice fed a high-fat-diet (HFD) or normal chow (NC) for 16 weeks, levels of VEGF-A were not significantly different between the two groups. However, levels of VEGF-C were significantly higher in HFD mice with advanced atherosclerosis and marked hypercholesterolemia than NC mice. Furthermore, immunohistochemistry revealed that the expression of VEGF-C in atheromatous plaque of the aortic sinus was significantly intensified by feeding HFD compared to NC, while that of VEGF-A was not. In conclusion, these findings demonstrate that VEGF-C, rather than VEGF-A, is closely related to dyslipidemia and atherosclerosis.Hiromichi WadaShuichi UraShuji KitaokaNoriko Satoh-AsaharaTakahiro HorieKoh OnoTomohide TakayaRieko Takanabe-MoriMasaharu AkaoMitsuru AbeTatsuya MorimotoToshinori MurayamaMasayuki YokodeMasatoshi FujitaAkira ShimatsuKoji HasegawaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e29351 (2011) |
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DOAJ |
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| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Hiromichi Wada Shuichi Ura Shuji Kitaoka Noriko Satoh-Asahara Takahiro Horie Koh Ono Tomohide Takaya Rieko Takanabe-Mori Masaharu Akao Mitsuru Abe Tatsuya Morimoto Toshinori Murayama Masayuki Yokode Masatoshi Fujita Akira Shimatsu Koji Hasegawa Distinct characteristics of circulating vascular endothelial growth factor-a and C levels in human subjects. |
| description |
The mechanisms that lead from obesity to atherosclerotic disease are not fully understood. Obesity involves angiogenesis in which vascular endothelial growth factor-A (VEGF-A) plays a key role. On the other hand, vascular endothelial growth factor-C (VEGF-C) plays a pivotal role in lymphangiogenesis. Circulating levels of VEGF-A and VEGF-C are elevated in sera from obese subjects. However, relationships of VEGF-C with atherosclerotic risk factors and atherosclerosis are unknown. We determined circulating levels of VEGF-A and VEGF-C in 423 consecutive subjects not receiving any drugs at the Health Evaluation Center. After adjusting for age and gender, VEGF-A levels were significantly and more strongly correlated with the body mass index (BMI) and waist circumference than VEGF-C. Conversely, VEGF-C levels were significantly and more closely correlated with metabolic (e.g., fasting plasma glucose, hemoglobin A1c, immunoreactive insulin, and the homeostasis model assessment of insulin resistance) and lipid parameters (e.g., triglycerides, total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and non-high-density-lipoprotein cholesterol (non-HDL-C)) than VEGF-A. Stepwise regression analyses revealed that independent determinants of VEGF-A were the BMI and age, whereas strong independent determinants of VEGF-C were age, triglycerides, and non-HDL-C. In apolipoprotein E-deficient mice fed a high-fat-diet (HFD) or normal chow (NC) for 16 weeks, levels of VEGF-A were not significantly different between the two groups. However, levels of VEGF-C were significantly higher in HFD mice with advanced atherosclerosis and marked hypercholesterolemia than NC mice. Furthermore, immunohistochemistry revealed that the expression of VEGF-C in atheromatous plaque of the aortic sinus was significantly intensified by feeding HFD compared to NC, while that of VEGF-A was not. In conclusion, these findings demonstrate that VEGF-C, rather than VEGF-A, is closely related to dyslipidemia and atherosclerosis. |
| format |
article |
| author |
Hiromichi Wada Shuichi Ura Shuji Kitaoka Noriko Satoh-Asahara Takahiro Horie Koh Ono Tomohide Takaya Rieko Takanabe-Mori Masaharu Akao Mitsuru Abe Tatsuya Morimoto Toshinori Murayama Masayuki Yokode Masatoshi Fujita Akira Shimatsu Koji Hasegawa |
| author_facet |
Hiromichi Wada Shuichi Ura Shuji Kitaoka Noriko Satoh-Asahara Takahiro Horie Koh Ono Tomohide Takaya Rieko Takanabe-Mori Masaharu Akao Mitsuru Abe Tatsuya Morimoto Toshinori Murayama Masayuki Yokode Masatoshi Fujita Akira Shimatsu Koji Hasegawa |
| author_sort |
Hiromichi Wada |
| title |
Distinct characteristics of circulating vascular endothelial growth factor-a and C levels in human subjects. |
| title_short |
Distinct characteristics of circulating vascular endothelial growth factor-a and C levels in human subjects. |
| title_full |
Distinct characteristics of circulating vascular endothelial growth factor-a and C levels in human subjects. |
| title_fullStr |
Distinct characteristics of circulating vascular endothelial growth factor-a and C levels in human subjects. |
| title_full_unstemmed |
Distinct characteristics of circulating vascular endothelial growth factor-a and C levels in human subjects. |
| title_sort |
distinct characteristics of circulating vascular endothelial growth factor-a and c levels in human subjects. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/76bf549c3929436993e223b0ecd1c549 |
| work_keys_str_mv |
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