Distinct Characteristics of Circulating Vascular Endothelial Growth Factor-A and C Levels in Human Subjects
| Autor: | Tatsuya Morimoto, Takahiro Horie, Tomohide Takaya, Akira Shimatsu, Rieko Takanabe-Mori, Masatoshi Fujita, Masayuki Yokode, Masaharu Akao, Toshinori Murayama, Hiromichi Wada, Shuji Kitaoka, Noriko Satoh-Asahara, Shuichi Ura, Mitsuru Abe, Koji Hasegawa, Koh Ono |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A medicine.medical_specialty Apolipoprotein B Angiogenesis Science medicine.medical_treatment Vascular Endothelial Growth Factor C Cardiovascular Biochemistry chemistry.chemical_compound Mice Insulin resistance Apolipoproteins E Vascular Biology Internal medicine medicine Animals Humans Obesity Biology Nutrition Multidisciplinary biology Cholesterol Insulin Middle Aged medicine.disease Lipid Metabolism Plaque Atherosclerotic Vascular endothelial growth factor A Endocrinology chemistry Vascular endothelial growth factor C Gene Expression Regulation Blood Chemistry biology.protein Medicine lipids (amino acids peptides and proteins) Female Dyslipidemia Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 12, p e29351 (2011) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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