Angiogenic factors are elevated in overweight and obese individuals

Silha, Josef V.; Kršek, Michal; Sucharda, P; Murphy, Liam

doi:10.1038/sj.ijo.0802987

Cited by 297 publications

(252 citation statements)

References 49 publications

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“…In vivo, Silha et al 21 reported that serum concentrations of VEGF were significantly elevated in human overweight and obese subjects. Matrix metalloproteases are produced by human adipose tissue, 22 and are expressed in adipose tissue during obesity and modulate adipocyte differentiation.…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro

et al. 2006

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Objective: Adipose tissue is closely associated with angiogenesis, but the mechanisms are not fully understood. Some of the adipocyte-derived cytokines are hypothesized to play an important role in angiogenesis. We evaluated tube formation of human umbilical vascular endothelial cells (HUVECs) cultured in type I collagen gel when overlaid with the supernatant of 3T3-L1 cell culture, and expression of tube-forming factor(s) in 3T3-L1 cells with or without pioglitazone. We also studied plasma growth factor levels in patients with type 2 diabetes mellitus treated with pioglitazone. Results and methods: The supernatant of 3T3-L1 cells increased tube formation of HUVECs by 9.03-fold of control. Reverse transcription-polymerase chain reaction showed that hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) mRNA were expressed in 3T3-L1 cells. Western blot analysis also demonstrated HGF and VEGF protein expression. When 3T3-L1 cells were treated with 100 nM small interfering RNAs (siRNAs) for HGF, the HGF mRNA and protein were suppressed. The VEGF mRNA and protein in the cells were also suppressed by siRNA for VEGF. The supernatant of 3T3-L1 cells treated with HGF siRNA suppressed tube formation of HUVECs by 61% compared with the supernatant of cells treated with control siRNA. Addition of VEGF siRNA resulted in no significant changes. The supernatant conditioned with pioglitazone further promoted the tube formation. Pioglitazone enhanced HGF mRNA expression in 3T3-L1 cells. After 12 weeks of pioglitazone treatment, the changes of plasma HGF levels in patients treated with pioglitazone were significantly higher than those in control. Conclusion: These results suggest that HGF secreted from 3T3-L1 cells may be the major factor regulating the tube formation, and agents that enhance the differentiation of adipocytes may promote tube formation of HUVECs mediated by HGF secreted by adipocytes.

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Section: Discussionmentioning

confidence: 99%

Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro

et al. 2006

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“…Macrophages reportedly accumulate within obese adipose tissue (11,28) so that the presence of macrophage markers is significantly and positively correlated with both adipocyte size and body mass (34). However, little is known about the roles such macrophages play in adipogenesis and obesity.…”

Section: Discussionmentioning

confidence: 99%

Adipogenesis in Obesity Requires Close Interplay Between Differentiating Adipocytes, Stromal Cells, and Blood Vessels

et al. 2007

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OBJECTIVE-The expansion of adipose tissue mass seen in obesity involves both hyperplasia and hypertrophy of adipocytes. However, little is known about how adipocytes, adipocyte precursors, blood vessels, and stromal cells interact with one another to achieve adipogenesis. RESEARCH DESIGN AND METHODS-We have developed a confocal microscopy-based method of three-dimensional visualization of intact living adipose tissue that enabled us to simultaneously evaluate angiogenesis and adipogenesis in db/db mice.RESULTS-We found that adipocyte differentiation takes place within cell clusters (which we designated adipogenic/angiogenic cell clusters) that contain multiple cell types, including endothelial cells and stromal cells that express CD34 and CD68 and bind lectin. There were close spatial and temporal interrelationships between blood vessel formation and adipogenesis, and the sprouting of new blood vessels from preexisting vasculature was coupled to adipocyte differentiation. CD34 ϩ CD68 ϩ lectin-binding cells could clearly be distinguished from CD34 Ϫ CD68 ϩ macrophages, which were scattered in the stroma and did not bind lectin. Adipogenic/angiogenic cell clusters can morphologically and immunohistochemically be distinguished from crownlike structures frequently seen in the late stages of adipose tissue obesity. Administration of anti-vascular endothelial growth factor (VEGF) antibodies inhibited not only angiogenesis but also the formation of adipogenic/angiogenic cell clusters, indicating that the coupling of adipogenesis and angiogenesis is essential for differentiation of adipocytes in obesity and that VEGF is a key mediator of that process. CONCLUSIONS-Living tissue imaging techniques providenovel evidence of the dynamic interactions between differentiating adipocytes, stromal cells, and angiogenesis in living obese adipose tissue. Diabetes

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“…Although it remains to be proven, it is likely that adipose tissue itself contributes to the elevated circulating levels of these factors. Therefore, adipose tissue may contribute to increased risk of metastatic disease in obese subjects with cancer (Silha et al, 2005).…”

Section: Expression Of Angiogenic Factors During Adipose Tissue Develmentioning

confidence: 99%

Angiogenesis and development of adipose tissue

Christiaens

Lijnen

2010

Molecular and Cellular Endocrinology

195

159

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Angiogenic factors are elevated in overweight and obese individuals

Cited by 297 publications

References 49 publications

Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro

Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro

Adipogenesis in Obesity Requires Close Interplay Between Differentiating Adipocytes, Stromal Cells, and Blood Vessels

Angiogenesis and development of adipose tissue

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