Soluble vascular endothelial growth factor, soluble VEGF receptor Flt-1 and endothelial function in healthy smokers

Schmidt-Lucke, Caroline; Belgore, F.; Reinhold, Dirk; Ansorge, Siegfried; Klein, Helmut U.; Schmidt-Lucke, Jan André; Lip, Gregory Y.H.

doi:10.1016/j.ijcard.2004.05.046

Cited by 26 publications

(23 citation statements)

References 22 publications

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“…In the present study, we demonstrated that CSE induced impaired VEGF-and FSS-mediated VEGFR2 activation and its downstream signaling in endothelial cells. This is supported by other studies indicating that long-term CS exposure downregulated VEGFR2 and VEGF expressions=levels in human and rodent lungs (16,27,35,50,53). Furthermore, VEGFR2 blockade caused endothelial cell apoptosis and transdifferentiation to smooth muscle-like and neuron-like cells (49).…”

Section: Fig 3 Cse Caused Nitration Of Tyrosine Residue In Vegfr2 Isupporting

confidence: 81%

Cigarette Smoke–induced Oxidative/Nitrosative Stress Impairs VEGF- and Fluid Shear Stress–Mediated Signaling in Endothelial Cells

Edirisinghe

Arunachalam

Wong

et al. 2010

Antioxidants & Redox Signaling

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VEGF receptor 2 (VEGFR2), a tyrosine kinase receptor, is activated by VEGF and fluid shear stress (FSS), and its downstream signaling is important in the regulation of endothelial functions, such as cell migration, endotheliumdependent relaxation, and angiogenesis. Cigarette smoke (CS) is known to cause oxidative=nitrosative stress, leading to modifications of tyrosine kinase receptors and impaired downstream signaling. We hypothesized that CS-induced oxidative=nitrosative stress impairs VEGF-and FSS-mediated VEGFR2 activation, leading to endothelial dysfunction. Human lung microvascular endothelial cells and human umbilical vein endothelial cells were treated with different concentrations of cigarette smoke extract (CSE) to investigate the VEGF-or FSS-mediated VEGFR2 phosphorylation and its downstream signaling involved in endothelial function. CSE treatment impaired both VEGF-and FSS-mediated VEGFR2 phosphorylation, resulting in impaired endothelial nitric oxide synthase (eNOS) phosphorylation by Akt. CS-derived reactive oxygen=nitrogen species react with VEGFR2, rendering VEGFR2 inactive for its downstream signaling. Pretreatment with nitric oxide scavenger (PTIO), reactive oxygen species scavengers (combination of SOD with catalase), and N-acetyl-l-cysteine, significantly attenuated the CSE-induced impairment of VEGF-mediated Akt and eNOS phosphorylation. These findings suggest that CSE-induced oxidative=nitrosative stress impairs VEGF-and FSS-mediated endothelial cell function and has important implications in the pathogenesis of CS-induced pulmonary and cardiovascular diseases associated with endothelial dysfunction. Antioxid. Redox Signal. 12, 1355-1369.

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Section: Fig 3 Cse Caused Nitration Of Tyrosine Residue In Vegfr2 Isupporting

confidence: 81%

Cigarette Smoke–induced Oxidative/Nitrosative Stress Impairs VEGF- and Fluid Shear Stress–Mediated Signaling in Endothelial Cells

Edirisinghe

Arunachalam

Wong

et al. 2010

Antioxidants & Redox Signaling

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“…Other human studies support this notion by showing that increased VEGF levels are associated with endothelial dysfunction (15,44). The VEGF is both an important marker of endothelial injury and mediator of repair.…”

Section: Discussionmentioning

confidence: 84%

Brief Secondhand Smoke Exposure Depresses Endothelial Progenitor Cells Activity and Endothelial Function

Heiß

Amabile

Lee

et al. 2008

Journal of the American College of Cardiology

264

159

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“…36,37 Similarly, pregnant women whose fetuses are affected by trisomy 13 (a condition associated with increased preeclampsia risk) have higher circulating sFlt1 levels as compared with control subjects, 38 possibly as a result of the extra copy of the sFlt1 gene, which resides on chromosome 13. Smoking is associated with both a reduced risk for preeclampsia 39,40 and lower circulating sFlt1 levels in both pregnant 33,41 and nonpregnant 42 individuals, as compared with nonsmokers. Cigarette smoke extract reduces sFlt1 production by placental cells in vitro.…”

Section: Recent Advances In Preeclampsiamentioning

confidence: 99%

Pregnancy and the Kidney

Maynard¹,

Thadhani²

2009

Journal of the American Society of Nephrology

181

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In recognizing renal disease, measurement of kidney function and proteinuria are the early standard bearers of subclinical pathology. With the dramatic hormonal and hemodynamic changes of pregnancy, renal function is altered and these changes must be considered when assessing renal function in pregnancy and in the choice of medications provided through parturition. Renal function and filtration are also affected in preeclampsia, and recent advances have greatly expanded our understanding of the pathophysiologic mechanisms of this pregnancy-specific renal syndrome. ASSESSMENT OF GFR AND PROTEINURIA DURING PREGNANCY Estimating GFR in PregnancyThe physiologic increase in GFR during pregnancy normally results in a decrease in concentration of serum creatinine, which falls by an average of 0.4 mg/dl to a pregnancy range of 0.4 to 0.8 mg/dl. 1 Hence, a serum creatinine of 1.0 mg/dl, although normal in a nonpregnant individual, reflects renal impairment in a pregnant woman. The Modification of Diet in Renal Disease (MDRD) formula, which estimates GFR using a combination of serum markers and clinical parameters, has become a standard clinical method to estimate renal function in patients with chronic kidney disease (CKD). The use of this formula has not been well studied in the pregnant population, and guidelines on application of the MDRD formula specifically exclude interpretation in pregnant women. Creatinine-based formulas developed in nonpregnant populations are likely to be inaccurate when applied to pregnant women. For example, the fall in serum creatinine during pregnancy reflects not only the pregnancy-induced increase in real GFR but also hemodilution resulting from the 30 to 50% plasma volume expansion by parturition. Perhaps more important, the MDRD formula systematically underestimates GFR as GFR rises above 60 ml/min per m 2 . This inherent inaccuracy is likely to be more pronounced at the high GFR of pregnancy.Weight-based formulas, such as Cockroft-Gault, might overestimate GFR because the increased body weight of pregnancy does not typically reflect increased muscle mass or creatinine production.In 2007, the accuracy of the MDRD formula in pregnant women was formally evaluated for the first time in two prospective studies. 2,3 Smith et al. 2 compared the performance of the modified MDRD formula (based on age, serum creatinine, and gender) with inulin clearance in three groups of women: healthy pregnant volunteers, women with preeclampsia, and pregnant women with CKD before pregnancy. Among healthy pregnant women, creatinine clearance by 24-h urine collection closely approximated GFR by inulin clearance; however, the MDRD underestimated GFR by Ͼ40 ml/min, a degree of bias that is somewhat higher than observed in nonpregnant kidney transplant donors with normal renal function (29 ml/min). 4 Among pregnant women with preeclampsia or CKD, the MDRD formula performed slightly better, underestimating GFR by 23.3 and 27.3 ml/min, respectively; however, the average GFR of all three groups Published online ahead ...

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Soluble vascular endothelial growth factor, soluble VEGF receptor Flt-1 and endothelial function in healthy smokers

Cited by 26 publications

References 22 publications

Cigarette Smoke–induced Oxidative/Nitrosative Stress Impairs VEGF- and Fluid Shear Stress–Mediated Signaling in Endothelial Cells

Cigarette Smoke–induced Oxidative/Nitrosative Stress Impairs VEGF- and Fluid Shear Stress–Mediated Signaling in Endothelial Cells

Brief Secondhand Smoke Exposure Depresses Endothelial Progenitor Cells Activity and Endothelial Function

Pregnancy and the Kidney

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