Preeclampsia and Future Cardiovascular Disease: Potential Role of Altered Angiogenesis and Insulin Resistance

Abstract Altered angiogenesis and insulin resistance are associated with preeclampsia and cardiovascular disease (CVD), and women with preeclampsia appear to be at increased risk of future CVD. We hypothesized that these factors are detectable in asymptomatic postpartum women with a history of preeclampsia and may represent pathophysiological mechanisms bridging preeclampsia and future CVD. We measured fasting insulin, glucose, vascular endothelial growth factor, and its circulating inhibitor, soluble fms-like tyrosine kinase (sFlt-1) in 29 normotensive women with a history of preeclampsia and 32 women with prior normotensive pregnancies at 18.0 ± 9.7 months postpartum. The homeostasis model of insulin resistance (HOMAIR) [(insulin [microunits per milliliter] × glucose [millimoles per liter])/22.5] was calculated. Compared with women with normal pregnancies, women with prior preeclampsia had significantly increased levels of sFlt-1 (41.6 ± 6.7 vs. 30.4 ± 10.2; P < 0.01) and median HOMAIR (2.8 vs. 1.9; P = 0.04). Membership in the upper quartile of either sFlt-1 or HOMAIR was associated with prior preeclampsia (odds ratio 5.7; 95% confidence interval 1.7, 20.0; P < 0.01), and all five women in the upper quartiles of both sFlt-1 and HOMAIR had a history of preeclampsia. Women with a history of preeclampsia demonstrate altered expression of angiogenesis-related proteins and increased HOMAIR more than 1 yr postpartum. These factors may contribute to their risk of future CVD.

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The Role of Fetuin-A in Disease Processes Prevalent in Postmenopausal Women (El papel de la fetuina A en los procesos de enfermedad prevalentes en mujeres posmenopáusicas)

Retos ◽

10.47197/retos.v0i27.34372 ◽

2015 ◽

pp. 172-179

Author(s):

Annie A. Bane ◽

Peter W. Grandjean

Keyword(s):

Insulin Resistance ◽

Cardiovascular Disease ◽

Postmenopausal Women ◽

Abdominal Fat ◽

Mineral Density ◽

Fetuin A ◽

Increased Risk ◽

Resistencia A La Insulina ◽

Low Levels

The purpose of this review is to summarize the role of fetuin-A in disease processes prevalent in postmenopausal women and synthesize effective interventions in obtaining healthy fetuin-A levels. A review of databases for articles related to fetuin-A and diseases associated with postmenopausal women was conducted. Articles were limited to full-text access, published in English since 1944. High fetuin-A levels are closely associated with decreased bone mineral density, increased cardiovascular disease risks, impairment of insulin signaling and disruption of adipocyte functioning. Postmenopausal women have increased risk of osteoporosis, cardiovascular disease, insulin-resistance, intra-abdominal fat accumulation and vascular calcification. Low-levels of fetuin-A have been shown to be protective against the latter. The role of fetuin-A is multi-factorial and the mechanisms in which it is involved in each of these processes are vast. The present body of literature is inconsistent in defining high versus low levels of fetuin-A and their association with healthy-matched controls. The diseases associated with high levels of fetuin-A mimic diseases most prevalent in postmenopausal women. In addition, there is no research, to date, exploring fetuin-A levels in postmenopausal women and the associations it may or may not have in related diseases.Key words: fetuin-A; Alpha2-Heremans-Schmid glycoprotein; cardiovascular disease; and elderly, insulin-resistance, intra-abdominal fat, metabolic syndrome, exercise, weight-loss, calorie restriction and postmenopausal.Resumen. El propósito de esta revisión es sintetizar el papel de la fetuina A en los procesos de enfermedad prevalentes en mujeres posmenopáusicas y resumir las intervenciones efectivas que permiten obtener niveles saludables de fetuina A. Para ello, se revisaron bases de datos con artículos relacionados con fetuina A y las enfermedades asociadas con mujeres posmenopáusicas. La búsqueda de artículos se limitó a aquellos de texto completo publicados en el idioma inglés desde el año 1944. Se encontró que altos niveles de fetuina A están íntimamente relacionados con una reducción de la densidad mineral ósea, un aumento en el riesgo de enfermedad cardiovascular, deterioro de la señalización de la insulina y la alteración del funcionamiento de los adipocitos. Las mujeres posmenopáusicas tienen un mayor riesgo de osteoporosis, enfermedad cardiovascular, resistencia a la insulina, acumulación de grasa intra abdominal y calcificación vascular. Se ha demostrado que niveles bajos de fetuina A son protectores contra esta última condición. El papel de fetuina A es multifactorial y los mecanismos en los que está involucrado en cada uno de estos procesos son muy amplios. El estado actual de la literatura no es consistente en la definición de niveles de fetuina A altos versus bajos y su asociación con controles sanos. Las enfermedades asociadas con altos niveles de fetuina A asemejan las enfermedades más prevalentes en mujeres posmenopáusicas. Además, no existen investigaciones, hasta la fecha, en las que se exploren los niveles de fetuina A en mujeres posmenopáusicas y las asociaciones que puede o no puede tener en las enfermedades relacionadas.Palabras claves: fetuina A, glicoproteína Alpha2-Heremans-Schmid, enfermedad cardiovascular, adulto mayor, resistencia a la insulina, grasa intra abdominal, síndrome metabólico, ejercicio, pérdida de peso, restricción calórica, posmenopausia.

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Viral and cellular cytokines in AIDS-related malignant lymphomatous effusions

Blood ◽

10.1182/blood.v96.4.1599 ◽

2000 ◽

Vol 96 (4) ◽

pp. 1599-1601 ◽

Cited By ~ 69

Author(s):

Yoshiyasu Aoki ◽

Robert Yarchoan ◽

James Braun ◽

Aikichi Iwamoto ◽

Giovanna Tosato

Keyword(s):

Vascular Endothelial Growth Factor ◽

Human Immunodeficiency Virus ◽

Potential Role ◽

Kaposi Sarcoma ◽

Enzyme Linked Immunosorbent Assay ◽

Vascular Endothelial ◽

Immunodeficiency Virus ◽

Endothelial Growth Factor ◽

Primary Effusion Lymphomas

Abstract Kaposi sarcoma-associated herpesvirus encodes viral IL-6 (vIL-6). To investigate the potential role of vIL-6 in the pathogenesis of human immunodeficiency virus (HIV)- related primary effusion lymphomas (PEL), a sensitive enzyme-linked immunosorbent assay was developed for vIL-6 and applied to the study of PEL. Whereas vIL-6 was detectable in 6 of 8 PEL effusions (range, 1390-66 630 pg/mL), it was not detectable in any of the control effusions. As expected, all PEL effusions contained human IL-6 (range, 957-37 494 pg/mL), and 7 of 8 contained detectable human IL-10 (range, 66-2,521,297 pg/mL). Human and vIL-6 have previously been shown to induce vascular endothelial growth factor, which in turn can increase vascular permeability. The results of the current study suggest that these cytokines play a central role in the pathogenesis and manifestations of PEL.

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The Potential Role of Vascular Endothelial Growth Factor in the Central Nervous System

Reviews in the Neurosciences ◽

10.1515/revneuro.2004.15.4.293 ◽

2004 ◽

Vol 15 (4) ◽

Cited By ~ 50

Author(s):

T. Yasuhara ◽

T. Shingo ◽

I. Date

Keyword(s):

Central Nervous System ◽

Vascular Endothelial Growth Factor ◽

Nervous System ◽

Growth Factor ◽

Potential Role ◽

Vascular Endothelial ◽

The Central Nervous System ◽

Endothelial Growth Factor

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Circadian System and Melatonin Hormone: Risk Factors for Complications during Pregnancy

Obstetrics and Gynecology International ◽

10.1155/2015/825802 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 22

Author(s):

F. J. Valenzuela ◽

J. Vera ◽

C. Venegas ◽

F. Pino ◽

C. Lagunas

Keyword(s):

Intrauterine Growth Restriction ◽

Clock Genes ◽

Circadian System ◽

Vascular Endothelial ◽

Local Production ◽

Intrauterine Growth ◽

Increased Risk ◽

Available Information ◽

Endothelial Growth Factor

Pregnancy is a complex and well-regulated temporal event in which several steps are finely orchestrated including implantation, decidualization, placentation, and partum and any temporary alteration has serious effects on fetal and maternal health. Interestingly, alterations of circadian rhythms (i.e., shiftwork) have been correlated with increased risk of preterm delivery, intrauterine growth restriction, and preeclampsia. In the last few years evidence is accumulating that the placenta may have a functional circadian system and express the clock genesBmal1,Per1-2, andClock. On the other hand, there is evidence that the human placenta synthesizes melatonin, hormone involved in the regulation of the circadian system in other tissues. Moreover, is unknown the role of this local production of melatonin and whether this production have a circadian pattern. Available information indicates that melatonin induces in placenta the expression of antioxidant enzymes catalase and superoxide dismutase, prevents the injury produced by oxidative stress, and inhibits the expression of vascular endothelial growth factor (VEGF) a gene that in other tissues is controlled by clock genes. In this review we aim to analyze available information regarding clock genes and clock genes controlled genes such as VEGF and the possible role of melatonin synthesis in the placenta.

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Pre-Eclamptic Pregnancies: An Opportunity to Identify Women at Risk for Future Cardiovascular Disease

Women s Health ◽

10.2217/17455057.4.2.133 ◽

2008 ◽

Vol 4 (2) ◽

pp. 133-135 ◽

Cited By ~ 25

Author(s):

Iasmina M Craici ◽

Steven J Wagner ◽

Suzanne R Hayman ◽

Vesna D Garovic

Keyword(s):

Systematic Review ◽

Cardiovascular Disease ◽

Risk Factor ◽

Meta Analysis ◽

Later Life ◽

Future Studies ◽

Increased Risk ◽

All Cause Mortality ◽

History Of

Evaluation of: Bellamy L, Casas JP, Hingorani AD, Williams DJ: Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. Br. Med. J. 335(7627), 974 (2007). Evidence has emerged over the years suggesting that women who develop hypertensive pregnancy disorders, most notably pre-eclampsia, are at an increased risk for cardiovascular disease later in life. In this study, a systematic review and meta-analysis were performed, assessing the future risks of cardiovascular disease, cancer and all-cause mortality in women with a history of pre-eclampsia and eclampsia. Women with a history of pre-eclampsia or eclampsia, compared with women without such a history, had an increased risk for cardiovascular disease, including a fourfold increased risk for hypertension, a twofold increased risk for ischemic heart disease, stroke and deep venous thrombosis, and a 1.5-times higher all-cause mortality. The study suggests that affected women may be eligible for preventive therapies at an earlier age, especially if future studies establish the role of pre-eclampsia as an independent cardiovascular risk factor.

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Viral and cellular cytokines in AIDS-related malignant lymphomatous effusions

Blood ◽

10.1182/blood.v96.4.1599.h8001599_1599_1601 ◽

2000 ◽

Vol 96 (4) ◽

pp. 1599-1601 ◽

Cited By ~ 4

Author(s):

Yoshiyasu Aoki ◽

Robert Yarchoan ◽

James Braun ◽

Aikichi Iwamoto ◽

Giovanna Tosato

Keyword(s):

Vascular Endothelial Growth Factor ◽

Human Immunodeficiency Virus ◽

Potential Role ◽

Kaposi Sarcoma ◽

Enzyme Linked Immunosorbent Assay ◽

Vascular Endothelial ◽

Immunodeficiency Virus ◽

Endothelial Growth Factor ◽

Primary Effusion Lymphomas

Kaposi sarcoma-associated herpesvirus encodes viral IL-6 (vIL-6). To investigate the potential role of vIL-6 in the pathogenesis of human immunodeficiency virus (HIV)- related primary effusion lymphomas (PEL), a sensitive enzyme-linked immunosorbent assay was developed for vIL-6 and applied to the study of PEL. Whereas vIL-6 was detectable in 6 of 8 PEL effusions (range, 1390-66 630 pg/mL), it was not detectable in any of the control effusions. As expected, all PEL effusions contained human IL-6 (range, 957-37 494 pg/mL), and 7 of 8 contained detectable human IL-10 (range, 66-2,521,297 pg/mL). Human and vIL-6 have previously been shown to induce vascular endothelial growth factor, which in turn can increase vascular permeability. The results of the current study suggest that these cytokines play a central role in the pathogenesis and manifestations of PEL.

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Incidence and management of bevacizumab associated hypertension in outpatient oncology clinic

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e20677 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e20677-e20677

Author(s):

C. Jee ◽

B. Brockstein ◽

W. Hui ◽

J. Lawton ◽

A. Harper ◽

...

Keyword(s):

Primary Care Physicians ◽

Retrospective Chart Review ◽

Vascular Endothelial ◽

Vegf Inhibitor ◽

Number Of Patients ◽

Increased Risk ◽

Wide Range ◽

History Of ◽

Grade 3 ◽

Endothelial Growth Factor

e20677 Background: Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor is utilized to treat a wide range of cancers. However, clinical trials of bevacizumab reported the incidence of hypertension (HTN) up to 36%. A national guideline has not been established to manage bevacizumab-induced HTN. The incidence and management of bevacizumab associated HTN were evaluated in an outpatient oncology clinic. Methods: A randomized, retrospective chart review of 100 patients who received at least one dose of bevacizumab from 1/1/07 to 12/31/07 was conducted. The overall incidence and management of hypertension were evaluated. Other bevacizumab associated toxicities were compared in patients with or without hypertension. Results: The overall incidence of bevacizumab-induced HTN was 31% (95%CI: 22%-40%) with CTC (v 3.0) grade 3 HTN rate of 10%. The number of patients with a history of HTN or uncontrolled BP prior to bevacizumab therapy was significantly different across the four HTN grade groups (p= 0.0019). Out of 31 patients who had grade 1–3 HTN, 8 patients (26%) were managed by the oncologists, 8 patients (26%) by the primary care physicians, and 15 patients (48%) had no management. Bevacizumab was held in 3 patients due to high blood pressure (BP) resulting in one patient discontinuing bevacizumab therapy. The odds of other bevacizumab associated adverse events in patients with grades 1–3 HTN was 2.776 times than that of patients with grade 0 HTN (p=0.0201). Conclusions: Bevacizumab was associated with HTN in 31% of patients. Patients with history of HTN or uncontrolled BP prior to initiating bevacizumab were at an increased risk to develop a higher grade of HTN. Management of bevacizumab-induced HTN could be improved since BP of 63% of patients with grades 2 and 3 HTN was not adequately controlled. No significant financial relationships to disclose.

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Genetic variants of vascular endothelial growth factor predict risk and survival of gliomas

Tumor Biology ◽

10.1177/1010428318766273 ◽

2018 ◽

Vol 40 (3) ◽

pp. 101042831876627 ◽

Cited By ~ 2

Author(s):

Paulo Linhares ◽

Marta Viana-Pereira ◽

Mónica Ferreira ◽

Júlia Amorim ◽

Rui Nabiço ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Odds Ratio ◽

Multiple Testing ◽

Cox Regression ◽

Vascular Endothelial ◽

Increased Risk ◽

Endothelial Growth Factor ◽

Vegf Polymorphisms

The vascular endothelial growth factor regulates angiogenesis that is increased in glioma. VEGF polymorphisms are thought to modulate vascular endothelial growth factor plasma levels and therefore may be implicated in glioma risk. We aimed to clarify the role of VEGF and von Willebrand factor polymorphisms in glioma susceptibility and prognosis. A case–control study of 126 glioma patients and 180 cancer-free controls was performed. Using Sequenom MassARRAY platform, 11 VEGF and 1 VWF polymorphisms were genotyped. Unconditional multivariate logistic regression models were used to calculate odds ratios and 95% confidence intervals. The associations between polymorphisms and survival were evaluated using a Cox regression model. Bonferroni’s adjustment was used to correct for multiple testing. The VEGF polymorphism rs833061 was strongly associated with increased risk for glioma (odds ratio = 164.85) and glioblastoma (odds ratio = 155.66), confirmed after Bonferroni correction. Also, the VEGF polymorphisms rs3024994, rs2010963, and particularly the homozygous carriers of rs1005230 were associated with a worse prognosis for glioma and glioblastoma. Our data support a role of VEGF and VWF polymorphisms as glioma biomarkers, with additional potential relevance for molecular stratification of patients for anti-angiogenic therapies.

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