Plasma endoglin as a marker to predict cardiovascular events in patients with chronic coronary artery diseases

Ikemoto, Tomokazu; Hojo, Yukihiro; Kondo, Hideyuki; Takahashi, Nobuhiro; Hirose, Masahiro; Nishimura, Yoshioki; Katsuki, Takaaki; Shimada, Kazuyuki; Kario, Kazuomi

doi:10.1007/s00380-011-0163-z

Cited by 52 publications

(44 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results are consistent with a previous report showing that plasma sEng concentration could serve as an indicator of diabetes-associated vascular pathologies such as retinopathy, hypertension, endothelial dysfunction, and cardiovascular risk [45]. Similarly, another study demonstrated that sEng could be a marker to predict cardiovascular events in patients with chronic coronary artery disease [46]. In addition, Li et al [28] showed that plasma sEng is a valuable surrogate angiogenic marker for identifying breast cancer patients who are at high risk of developing metastasis.…”

Section: Discussionsupporting

confidence: 93%

High-Mobility Group Box-1 and Endothelial Cell Angiogenic Markers in the Vitreous from Patients with Proliferative Diabetic Retinopathy

El‐Asrar

Nawaz

Kangave

et al. 2012

Mediators of Inflammation

View full text Add to dashboard Cite

The aim of this study was to measure the levels of high-mobility group box-1 (HMGB1) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate its levels with clinical disease activity and the levels of vascular endothelial growth factor (VEGF), the angiogenic cytokine granulocyte-colony-stimulating factor (G-CSF), the endothelial cell angiogenic markers soluble vascular endothelial-cadherin (sVE-cadherin), and soluble endoglin (sEng). Vitreous samples from 36 PDR and 21 nondiabetic patients were studied by enzyme-linked immunosorbent assay. HMGB1, VEGF, sVE-cadherin, and sEng levels were significantly higher in PDR patients than in nondiabetics (P = 0.008; <0.001; <0.001; 0.003, resp.). G-CSF was detected in only 3 PDR samples. In the whole study group, there was significant positive correlation between the levels of HMGB1, and sVE-cadherin (r = 0.378, P = 0.007). In PDR patients, there was significant negative correlation between the levels of sVE-cadherin and sEng (r = −0.517, P = 0.0005). Exploratory regression analysis identified significant associations between active PDR and high levels of VEGF (odds ratio = 76.4; 95% confidence interval = 6.32–923) and high levels of sEng (odds ratio = 6.01; 95% confidence interval = 1.25–29.0). Our findings suggest that HMGB1, VEGF, sVE-cadherin and sEng regulate the angiogenesis in PDR.

show abstract

Section: Discussionsupporting

confidence: 93%

High-Mobility Group Box-1 and Endothelial Cell Angiogenic Markers in the Vitreous from Patients with Proliferative Diabetic Retinopathy

El‐Asrar

Nawaz

Kangave

et al. 2012

Mediators of Inflammation

View full text Add to dashboard Cite

show abstract

“…The magnitude of the differences in sEng concentrations between hypertensive OSA and control groups in our study is comparable to those seen with target organ damage and hypertension and in those with high risk for cardiovascular adverse outcome. 29,30 The mechanism for elevated sEng levels in OSA is unknown. However, there are several possibilities.…”

Section: Discussionmentioning

confidence: 99%

Endothelial dysfunction and hypertension in obstructive sleep apnea – Is it due to intermittent hypoxia?

Jafari

Mohsenin

2013

Journal of Cardiovascular Disease Research

View full text Add to dashboard Cite

a b s t r a c tBackground: Obstructive sleep apnea (OSA) is a prevalent disorder causing hypertension. Endothelial dysfunction appears to underlie development of hypertension. It is not known whether hypoxia during sleep is necessarily the prerequisite process for endothelial dysfunction and hypertension in OSA. We therefore examined the relationship between endothelial-dependent vasodilatory capacity, hypoxia and circulating angiogenesis inhibitors in OSA. Methods and results:We studies 95 subjects with and without OSA and hypertension. Endothelialdependent vasodilation was assessed using brachial artery flow-mediated vasodilation method (FMD). Plasma angiogenesis inhibitors, endoglin (sEng) and fms-like tyrosine kinase-1 (sFlt-1), were measured using ELISA. The apneaehypopnea indexes were 41 AE 5 and 48 AE 4 events/hr in normotensive OSA (N-OSA) and hypertensive OSA (H-OSA), respectively, indicating severe OSA. The sleep time spent with SaO 2 < 90% (T < 90%) were 34 AE 8 and 40 AE 9 min, respectively. FMD was markedly impaired in H-OSA (8.0% AE 0.5) compared to N-OSA (13.5% AE 0.5, P < 0.0001), H-non-OSA (10.5% AE 0.8, P < 0.01), and N-non-OSA (16.1% AE 1.0, P < 0.0001). There was no correlation between T < 90% and FMD. Both OSA groups had elevated levels of sFlt-1 (62.4 AE 5.9 and 63.9 AE 4.7 pg/ml) compared to N-non-OSA (32.1 AE 6.5, P ¼ 0.0008 and P ¼ 0.0004, respectively) and H-non-OSA (41.2 AE 7.0, P < 0.05 and P ¼ 0.03, respectively). In contrast, sEng was only elevated in H-OSA (4.20 AE 0.17 ng/ml) compared with N-OSA (3.64 AE 0.14, P ¼ 0.01) and N-non-OSA (3.48 AE 0.20, P ¼ 0.01). There was a modest but statistically significant inverse correlation between sEng and FMD in only H-OSA group (r ¼ À0.38, P < 0.05). Conclusion: These data show that patients with OSA and hypertension have marked impairment of FMD, independent of hypoxia exposure, which is associated with increased sEng.Copyright Ó 2013, SciBioIMed.Org, Published by Reed Elsevier India Pvt. Ltd. All rights reserved. Key MessagesObstructive sleep apnea is a highly prevalent disorder with associated high morbidity and mortality. Obstructive sleep apnea is now considered as one of the causes of systemic hypertension. No all patients with obstructive sleep apnea develop hypertension. There appears to be divergent responses to apnea-associated hypoxia. In this article a group of patients with severe obstructive sleep apnea and hypoxia exposure during sleep had normal blood pressure and relatively preserved endothelial-dependent vasodilatory capacity. A comparable group of patients with similar apnea severity and hypoxia exposure had marked impairment in endothelial-dependent vasodilatory capacity and hypertension. This group had significantly elevated circulating levels of soluble endoglin, an angiogenesis inhibitor, with known effect on endothelial function and development of hypertension. It is conceivable that inflammatory state of obstructive sleep apnea provokes release of angiogenesis inhibitors causing downstream perturbation of endothelial...

show abstract

“…In addition, spontaneous AVMs, the most frequent cause of cerebral haemorrhage in the young, may relate to abnormal function of ENG or ACVRL1 genes. In the context of general cardiovascular health, circulating Sol-Eng is not only an important biomarker of pre-eclampsia, but also a predictor of cardiovascular events in chronic coronary artery disease patients [68]. It is almost certain that further fundamental roles of endoglin and ACVRL1 in the cardiovasculature will be revealed in the near future.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Angiogenesis regulation by TGFβ signalling: clues from an inherited vascular disease

Mahmoud

Upton

Arthur

2011

Biochemical Society Transactions

View full text Add to dashboard Cite

Studies of rare genetic diseases frequently reveal genes that are fundamental to life, and the familial vascular disorder HHT (hereditary haemorrhagic telangiectasia) is no exception. The majority of HHT patients are heterozygous for mutations in either the ENG (endoglin) or the ACVRL1 (activin receptor-like kinase 1) gene. Both genes are essential for angiogenesis during development and mice that are homozygous for mutations in Eng or Acvrl1 die in mid-gestation from vascular defects. Recent development of conditional mouse models in which the Eng or Acvrl1 gene can be depleted in later life have confirmed the importance of both genes in angiogenesis and in the maintenance of a normal vasculature. Endoglin protein is a co-receptor and ACVRL1 is a signalling receptor, both of which are expressed primarily in endothelial cells to regulate TGFβ (transforming growth factor β) signalling in the cardiovasculature. The role of ACVRL1 and endoglin in TGFβ signalling during angiogenesis is now becoming clearer as interactions between these receptors and additional ligands of the TGFβ superfamily, as well as synergistic relationships with other signalling pathways, are being uncovered. The present review aims to place these recent findings into the context of a better understanding of HHT and to summarize recent evidence that confirms the importance of endoglin and ACVRL1 in maintaining normal cardiovascular health.

show abstract

Plasma endoglin as a marker to predict cardiovascular events in patients with chronic coronary artery diseases

Cited by 52 publications

References 31 publications

High-Mobility Group Box-1 and Endothelial Cell Angiogenic Markers in the Vitreous from Patients with Proliferative Diabetic Retinopathy

High-Mobility Group Box-1 and Endothelial Cell Angiogenic Markers in the Vitreous from Patients with Proliferative Diabetic Retinopathy

Endothelial dysfunction and hypertension in obstructive sleep apnea – Is it due to intermittent hypoxia?

Angiogenesis regulation by TGFβ signalling: clues from an inherited vascular disease

Contact Info

Product

Resources

About