The relationship between circulating endothelin-1, soluble fms-like tyrosine kinase-1 and soluble endoglin in preeclampsia

Aggarwal, Poonam; Chandel, Nirupama; Jain, Vanita; Jha, Vivekanand

doi:10.1038/jhh.2011.29

Cited by 88 publications

(75 citation statements)

References 32 publications

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“…Levels of sFlt1 and sEng both correlated with mean arterial pressure (data not shown) similar to previous studies. 32 When diastolic function was calculated using the definition used by Melchiorre et al, 19 we found significant higher sFlt1 and sEng levels and a worse GLS in the pathological group defined as lateral E′ <14 cm/s (all P<0.001).…”

Section: Correlation Between Angiogenic Factors and Echocardiography mentioning

confidence: 61%

Circulating Antiangiogenic Factors and Myocardial Dysfunction in Hypertensive Disorders of Pregnancy

et al. 2016

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H ypertensive disorders of pregnancy (HDP) affect 5% to 10% of pregnant women, 1 are the most common medical complication of pregnancy in developed countries, 2 and are a leading cause of maternal and fetal death worldwide. 3 HDP include preeclampsia, gestational hypertension, chronic hypertension, and superimposed preeclampsia. Preeclampsia targets the vascular endothelium causing widespread maternal vascular endothelial dysfunction. Antiangiogenic proteins have been implicated as being pathogenic in the development of the observed vascular endothelial dysfunction. 4Overexpression of soluble fms-like tyrosine kinase-1 (sFlt1), an endogenous vascular endothelial growth factor inhibitor, is associated with preeclampsia-like phenotypes in a rodent model and symptoms diminish with the addition of vascular endothelial growth factor or placental growth factor. [5][6][7] Multiple human clinical studies have established that levels of the sFlt1 and soluble endoglin (sEng) increase in the circulation of pregnant women with preeclampsia. 4,6,[8][9][10] sFlt1 and sEng levels are elevated weeks before the clinical onset of preeclampsia, and the degree of elevation correlates with adverse maternal and fetal outcomes. 8,[11][12][13][14][15][16] Few adverse outcomes occur in the absence of angiogenic factor abnormalities. 17,18 Although previous studies have detected changes in myocardial function in HDP, 19,20 a direct association between preeclampsia biomarkers, including sFlt1 and sEng, has not been described. In other abnormal cardiovascular states such as congestive heart failure, increased circulating levels of antiangiogenic proteins have been associated with development of endothelial vascular dysfunction, myocardial dysfunction, and adverse cardiovascular outcomes. 21Women with HDP have abnormalities in both systolic and diastolic cardiac function that seem before clinical symptoms.19,22 Despite preservation of left ventricular ejection fraction (LVEF), 23 longitudinal muscle fiber shortening is decreased, suggesting the presence of subclinical left ventricular systolic dysfunction. 20 This finding suggests a Abstract-Hypertensive disorders of pregnancy (HDP) are associated with subclinical changes in cardiac function. Although the mechanism underlying this finding is unknown, elevated levels of soluble antiangiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng) are associated with myocardial dysfunction and may play a role. We hypothesized that these antiangiogenic proteins may contribute to the development of cardiac dysfunction in HDP. We prospectively studied 207 pregnant women with HDP and nonhypertensive controls and evaluated whether changes in global longitudinal strain (GLS) observed on echocardiography is specific for HDP and whether these changes correlate with HDP biomarkers, sFlt1 and sEng. A total of 62 (30%) patients were diagnosed with preeclampsia (group A), 105 (51%) did not have an HDP (group B), and 40 (19%) were diagnosed with chronic or gestational hype...

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Section: Correlation Between Angiogenic Factors and Echocardiography mentioning

confidence: 61%

Circulating Antiangiogenic Factors and Myocardial Dysfunction in Hypertensive Disorders of Pregnancy

et al. 2016

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“…In recent studies, this activation of the ET-1 system in preeclamptic or in HELLP syndrome pregnancies has been confirmed by different research groups [1 && , 3,4], and, most interestingly, this elevation of circulating ET-1 levels in preeclampsia has been shown to be closely related to the increased sFlt-1 levels in this syndrome [1 && ,3]. Activation of the endothelin system has repeatedly been reported in clinical preeclampsia, and also in different experimental preeclampsia models.…”

Section: Elevated Endothelin In Preeclampsiamentioning

confidence: 67%

Role of endothelin in preeclampsia and hypertension following antiangiogenesis treatment

Saleh

Danser

Meiracker

2016

Current Opinion in Nephrology and Hypertension

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“…This result was in agreement with other animal and human studies that reported a high correlation between sENG and sFlt-1 on one hand and disease severity on the other hand. 26,27 A causal relationship between these antiangiogenic growth factors and fetal mortality in PE is strongly suggested by the observed negative correlation between sENG/sFlt-1 and the number of live pups and their birth weight (Figure 1c and d, Figure 2a-c) and the direct correlation between sENG and the number of dead pups (Figure 2d).…”

Section: Discussionmentioning

confidence: 94%

Magnesium sulfate therapy of preeclampsia: an old tool with new mechanism of action and prospect in management and prophylaxis

Korish

2012

Hypertens Res

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A disturbed balance between angiogenic and antiangiogenic growth factors is a highly accepted mechanism in the pathogenesis of pregnancy-induced hypertension and proteinuria, which is clinically known as preeclampsia (PE). We investigated the effect of magnesium sulfate (MgSO 4 ) therapy on vascular endothelial growth factor (VEGF), placental growth factor (PlGF), nitric oxide (NO) metabolites, soluble fm-like tyrosine kinase-1 (sFlt-1) and endoglin levels in PE rats and the effect of this treatment on the feto-maternal outcome. The PE group showed hypertension, proteinuria and decreased number and weight of live pups relative to the control group. This result was associated with increased sFlt-1, VEGF receptor-2 (VEGFR-2), VEGFR-3 and endoglin levels but decreased NO metabolites. MgSO 4 therapy ameliorated systolic hypertension and proteinuria and decreased sFlt-1, VEGFR-2, VEGFR-3 and endoglin levels but increased NO metabolites in the treated group. Physiological and biochemical changes and improved pup weight and viability were observed in the treated group. The vasodilator action of MgSO 4 and increased NO production are expected to increase placental blood flow and help fetal nutrition and development. Relief of placental ischemia decreases the production of antiangiogenic growth factors and restores the bioavailability of angiogenic factors (PlGF and VEGF). These changes resulted in better fetal outcome and an improved clinical picture of PE. These findings are promising and encourage further study of the mechanism of action of MgSO 4 to support its widespread use in the prevention and management of the etiopathological changes underlying the vast majority of the manifestations and complications of PE.

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The relationship between circulating endothelin-1, soluble fms-like tyrosine kinase-1 and soluble endoglin in preeclampsia

Cited by 88 publications

References 32 publications

Circulating Antiangiogenic Factors and Myocardial Dysfunction in Hypertensive Disorders of Pregnancy

Circulating Antiangiogenic Factors and Myocardial Dysfunction in Hypertensive Disorders of Pregnancy

Role of endothelin in preeclampsia and hypertension following antiangiogenesis treatment

Magnesium sulfate therapy of preeclampsia: an old tool with new mechanism of action and prospect in management and prophylaxis

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