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Peripheral monocytes from diabetic patients with coronary artery disease display increased bFGF and VEGF mRNA expression.

Panutsopulos D, Zafiropoulos A, Krambovitis E, Kochiadakis GE, Igoumenidis NE, Spandidos DA - J Transl Med (2003)

Bottom Line: Seventeen were found to be healthy and 36 were diagnosed with CAD.RESULTS: The statistical analysis revealed a significant increase of the basal level expression for macrophage VEGF and bFGF in the CAD SA (stable angina) patient group compared to the noCAD (control) (p = 0.041 and p = 0.022 respectively) and CAD UA (unstable angina) (p = 0.024 and p = 0.005 respectively) groups, which was highly dependent on the diabetic status of the population.The results give new insight to CAD and the impaired collateral vessel formation in diabetics.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Virology, Medical School, University of Crete, Heraklion, Crete, Greece. spandidos@spandidos.gr

ABSTRACT
BACKGROUND: Macrophages can produce vascular endothelial growth factor (VEGF) in response to hypoxia, transforming growth factor beta1 (TGF-beta1), angiotensin II, basic fibroblast growth factor (bFGF), and interleukin-1. These factors have been found in the serum of coronary artery disease (CAD) patients as well as in atherosclerotic lesions. The aim of the present study was to test the hypothesis that the expression of VEGF, TGF-beta1 and bFGF in peripheral monocytes and lymphocytes is related to CAD. METHODS: Human Mononuclear cells and lymphocytes from peripheral blood were isolated from 53 donors undergoing angiography. Seventeen were found to be healthy and 36 were diagnosed with CAD. The respective mRNAs were extracted and quantified. RESULTS: The statistical analysis revealed a significant increase of the basal level expression for macrophage VEGF and bFGF in the CAD SA (stable angina) patient group compared to the noCAD (control) (p = 0.041 and p = 0.022 respectively) and CAD UA (unstable angina) (p = 0.024 and p = 0.005 respectively) groups, which was highly dependent on the diabetic status of the population. Furthermore, we demonstrated with an in vitro cell culture model that the levels of VEGF and bFGF in monocytes of healthy donors are not affected by short term exposure to increased glucose levels (usually observed in the diabetic patients) and/or statin. CONCLUSION: Our findings display a statistically significant association of the increased VEGF and bFGF levels in peripheral monocytes, with stable angina and diabetes in coronary artery disease. The results give new insight to CAD and the impaired collateral vessel formation in diabetics.

No MeSH data available.


Related in: MedlinePlus

Analysis of the effect of glucose and fluvastatin on the kinetics of mRNA expression of VEGF (–▪–) and bFGF (–•–) in normal monocytes/macrophages during a 48 hour in vitro treatment period. A, no treatment. B, treatment with glucose (6 mg/ml). C, treatment with fluvastatin (1 μM). D, treatment with glucose and Fluvastatin. The y-axis represents the VEGF/β2-microglobulin and bFGF/β2-microglobulin ratio of the integrated density respectively.
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Figure 2: Analysis of the effect of glucose and fluvastatin on the kinetics of mRNA expression of VEGF (–▪–) and bFGF (–•–) in normal monocytes/macrophages during a 48 hour in vitro treatment period. A, no treatment. B, treatment with glucose (6 mg/ml). C, treatment with fluvastatin (1 μM). D, treatment with glucose and Fluvastatin. The y-axis represents the VEGF/β2-microglobulin and bFGF/β2-microglobulin ratio of the integrated density respectively.

Mentions: Furthermore we analyzed in the above model the effect of high glucose levels found in diabetic individuals and statins found in the medication of all our patients on the mRNA levels of VEGF and bFGF during a 48 hour period. We isolated a blood sample from healthy donor 1 in an identical fashion to those from patients from the catheterization laboratory and set cultures with appropriate concentrations of glucose, statin and glucose+statin. After the 1 hour attachment period the cultures were harvested at specific time intervals (30 min, 1 h, 2, 4, 24 h, 48 h) and the mRNA of VEGF and bFGF was quantified. The results show a gradual time dependent decrease of both mRNA levels (Figure 2) which was not affected by glucose or statin. The experiment was repeated with a different donor and the results were similar. Although the initial values of bFGF and VEGF differed slightly, consistent with the donor variation, the trend for decline of expression was the same. These results should be evaluated in the context of our in vitro system since in vivo gene expression is not always the same.


Peripheral monocytes from diabetic patients with coronary artery disease display increased bFGF and VEGF mRNA expression.

Panutsopulos D, Zafiropoulos A, Krambovitis E, Kochiadakis GE, Igoumenidis NE, Spandidos DA - J Transl Med (2003)

Analysis of the effect of glucose and fluvastatin on the kinetics of mRNA expression of VEGF (–▪–) and bFGF (–•–) in normal monocytes/macrophages during a 48 hour in vitro treatment period. A, no treatment. B, treatment with glucose (6 mg/ml). C, treatment with fluvastatin (1 μM). D, treatment with glucose and Fluvastatin. The y-axis represents the VEGF/β2-microglobulin and bFGF/β2-microglobulin ratio of the integrated density respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC239962&req=5

Figure 2: Analysis of the effect of glucose and fluvastatin on the kinetics of mRNA expression of VEGF (–▪–) and bFGF (–•–) in normal monocytes/macrophages during a 48 hour in vitro treatment period. A, no treatment. B, treatment with glucose (6 mg/ml). C, treatment with fluvastatin (1 μM). D, treatment with glucose and Fluvastatin. The y-axis represents the VEGF/β2-microglobulin and bFGF/β2-microglobulin ratio of the integrated density respectively.
Mentions: Furthermore we analyzed in the above model the effect of high glucose levels found in diabetic individuals and statins found in the medication of all our patients on the mRNA levels of VEGF and bFGF during a 48 hour period. We isolated a blood sample from healthy donor 1 in an identical fashion to those from patients from the catheterization laboratory and set cultures with appropriate concentrations of glucose, statin and glucose+statin. After the 1 hour attachment period the cultures were harvested at specific time intervals (30 min, 1 h, 2, 4, 24 h, 48 h) and the mRNA of VEGF and bFGF was quantified. The results show a gradual time dependent decrease of both mRNA levels (Figure 2) which was not affected by glucose or statin. The experiment was repeated with a different donor and the results were similar. Although the initial values of bFGF and VEGF differed slightly, consistent with the donor variation, the trend for decline of expression was the same. These results should be evaluated in the context of our in vitro system since in vivo gene expression is not always the same.

Bottom Line: Seventeen were found to be healthy and 36 were diagnosed with CAD.RESULTS: The statistical analysis revealed a significant increase of the basal level expression for macrophage VEGF and bFGF in the CAD SA (stable angina) patient group compared to the noCAD (control) (p = 0.041 and p = 0.022 respectively) and CAD UA (unstable angina) (p = 0.024 and p = 0.005 respectively) groups, which was highly dependent on the diabetic status of the population.The results give new insight to CAD and the impaired collateral vessel formation in diabetics.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Virology, Medical School, University of Crete, Heraklion, Crete, Greece. spandidos@spandidos.gr

ABSTRACT
BACKGROUND: Macrophages can produce vascular endothelial growth factor (VEGF) in response to hypoxia, transforming growth factor beta1 (TGF-beta1), angiotensin II, basic fibroblast growth factor (bFGF), and interleukin-1. These factors have been found in the serum of coronary artery disease (CAD) patients as well as in atherosclerotic lesions. The aim of the present study was to test the hypothesis that the expression of VEGF, TGF-beta1 and bFGF in peripheral monocytes and lymphocytes is related to CAD. METHODS: Human Mononuclear cells and lymphocytes from peripheral blood were isolated from 53 donors undergoing angiography. Seventeen were found to be healthy and 36 were diagnosed with CAD. The respective mRNAs were extracted and quantified. RESULTS: The statistical analysis revealed a significant increase of the basal level expression for macrophage VEGF and bFGF in the CAD SA (stable angina) patient group compared to the noCAD (control) (p = 0.041 and p = 0.022 respectively) and CAD UA (unstable angina) (p = 0.024 and p = 0.005 respectively) groups, which was highly dependent on the diabetic status of the population. Furthermore, we demonstrated with an in vitro cell culture model that the levels of VEGF and bFGF in monocytes of healthy donors are not affected by short term exposure to increased glucose levels (usually observed in the diabetic patients) and/or statin. CONCLUSION: Our findings display a statistically significant association of the increased VEGF and bFGF levels in peripheral monocytes, with stable angina and diabetes in coronary artery disease. The results give new insight to CAD and the impaired collateral vessel formation in diabetics.

No MeSH data available.


Related in: MedlinePlus