Expression and secretion of neuregulin-1 in cardiac microvascular endothelial cells treated with angiogenic factors

Wu, Chengqiang; Gui, Chun; Li, Lang; Pang, Yiheng; Tang, Zhongli; Wei, Jing

doi:10.3892/etm.2018.5811

Cited by 15 publications

(15 citation statements)

References 23 publications

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“…In the myocardium, NRG1 is primarily produced by the microvascular endothelium in response to mechanical stretch, oxidative stress, and hypoxia . NRG1/ErbB signalling and NRG1 are suggested to increase the number of microvessels in post‐ischaemic animal models . Further, demonstrating the link between endothelial dysfunction and oxidative stress, we found that NRG1‐β correlated with the oxidative stress marker IGFBP‐1 in our patients with HFrEF.…”

Section: Discussionsupporting

confidence: 57%

Circulating neuregulin1‐β in heart failure with preserved and reduced left ventricular ejection fraction

et al. 2020

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Aims Neuregulin1-β (NRG1-β) is released from microvascular endothelial cells in response to inflammation with compensatory cardioprotective effects. Circulating NRG1-β is elevated in heart failure (HF) with reduced ejection fraction (HFrEF) but not studied in HF with preserved EF (HFpEF). Methods and results Circulating NRG1-β was quantified in 86 stable patients with HFpEF (EF ≥45% and N-terminal pro-brain natriuretic peptide >300 ng/L), in 86 patients with HFrEF prior to and after left ventricular assist device (LVAD) and/or heart transplantation (HTx) and in 21 healthy controls. Association between NRG1-β and the composite outcome of all-cause mortality/HF hospitalization in HFpEF and all-cause mortality/HTx/LVAD implantation in HFrEF with and without ischaemia assessed as macrovascular coronary artery disease was assessed. In HFpEF, median (25th-75th percentile) NRG1-β was 6.5 (2.1-11.3) ng/mL; in HFrEF, 3.6 (2.1-7.6) ng/mL (P = 0.035); after LVAD, 1.7 (0.9-3.6) ng/mL; after HTx 2.1 (1.4-3.6) ng/mL (overall P < 0.001); and in controls, 29.0 (23.1-34.3) ng/mL (P = 0.001). In HFrEF, higher NRG1-β was associated with worse outcomes (hazard ratio per log increase 1.45, 95% confidence interval 1.04-2.03, P = 0.029), regardless of ischaemia. In HFpEF, the association of NRG1-β with outcomes was modified by ischaemia (log-rank P = 0.020; P interaction = 0.553) such that only in ischaemic patients, higher NRG1-β was related to worse outcomes. In contrast, in patients without ischaemia, higher NRG1-β trended towards better outcomes (hazard ratio 0.71, 95% confidence interval 0.48-1.05, P = 0.085). Conclusions Neuregulin1-β was reduced in HFpEF and further reduced in HFrEF. The opposing relationships of NRG1-β with outcomes in non-ischaemic HFpEF compared with HFrEF and ischaemic HFpEF may indicate compensatory increases of cardioprotective NRG1-β from microvascular endothelial dysfunction in the former (non-ischaemic HFpEF), but this compensatory mechanism is overwhelmed by the presence of ischaemia in the latter (HFrEF and ischaemic HFpEF).

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Section: Discussionsupporting

confidence: 57%

Circulating neuregulin1‐β in heart failure with preserved and reduced left ventricular ejection fraction

et al. 2020

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“…HER2 is essential throughout the cardiovascular system [11][12][13], and its extracellular domain shedding process make it highly expressed in the bloodstream [5]. Of note, our data showed that the difference in circulating HER2 levels between CAD and control groups was not strikingly huge.…”

Section: Discussionmentioning

confidence: 63%

“…HER2 is abundantly expressed throughout the cardiovascular system, including by endothelial cells, vascular smooth muscle cells (SMCs), and cardiomyocytes [11][12][13]. Previous studies found that the HER family, particularly EGFR and HER2, contribute to the pathogenesis of vascular remodeling and atherosclerosis, such as oxidative stress, macrophage infiltration, and SMC proliferation and migration [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Association between serum HER2/ErbB2 levels and coronary artery disease: a case–control study

et al. 2020

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Background: Research has associated human epidermal growth factor receptor (HER2) with glucose and lipid metabolism. However, the association between circulating HER2 levels and coronary artery disease (CAD) remains to be elucidated. Methods: We performed a case-control study with 435 participants (237 CAD patients and 198 controls) who underwent diagnostic coronary angiography from September 2018 to October 2019. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CAD were calculated with multiple logistic regression models after adjustment for confounders. Results: Overall, increased serum HER2 levels were independently associated with the presence of CAD (OR per 1-standard deviation (SD) increase: 1.438, 95% CI 1.13-1.83; P = 0.003) and the number of stenotic vessels (OR per 1-SD increase: 1.399, 95% CI 1.15-1.71; P = 0.001). In the subgroup analysis, a significant interaction of HER2 with body mass index (BMI) on the presence of CAD was observed (adjusted interaction P = 0.046). Increased serum HER2 levels were strongly associated with the presence of CAD in participants with BMI ≥ 25 kg/m 2 (OR per 1-SD increase: 2.143, 95% CI 1.37-3.35; P = 0.001), whereas no significant association was found in participants with BMI < 25 kg/m 2 (OR per 1-SD increase: 1.225, 95% CI 0.90-1.67; P = 0.201). Conclusion: Elevated HER2 level is associated with an increased risk of CAD, particularly in people with obesity. This finding yields new insight into the pathological mechanisms underlying CAD, and warrants further research regarding HER2 as a preventive and therapeutic target of CAD.

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“…11) However, another study has revealed that the expression and release of NRG-1 were significantly increased in human cardiac microvascular endothelial cells under VEGF and Ang-1 stimulation, which suggested that these angiogenic factors could regulate NRG-1 signaling pathway. 14) Although there is no conclusion of the precious casual association among VEGF, Ang-1, and NRG-1, we can speculate that there may be a positive feedback among VEGF/ Ang-1-NRG-1 signaling pathways. Consistent with these findings, our results have demonstrated that NRG-1, VEGF, and Ang-1 were all significantly increased in good CCC group, and there was a positive correlation among them.…”

Section: Discussionmentioning

confidence: 80%

“…13) In addition, NRG-1 has been shown to promote myocardial angiogenesis in the ischemic and diabetic myocardium and is involved in the vascular endothelial growth factor (VEGF) / Angiopoietin-1(Ang-1) angiogenesis signaling events. 11,14,15) These findings revealed that NRG-1 might participate in the development of CCC and could function as a potential biomarker. However, the association between NRG-1 and CCC has not been explored in CAD patients.…”

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confidence: 74%

The Relationship Between Circulating Neuregulin-1 and Coronary Collateral Circulation in Patients with Coronary Artery Disease

et al. 2020

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Coronary collateral circulation (CCC) plays a crucial role in myocardial blood supply, especially for ischemic myocardium. Previous study has shown that neuregulin-1 is a prominent angiogenic factor in diabetic cardiomyopathy, whereas the relationship between neuregulin-1 and CCC has not been investigated. Thus, we aimed to investigate relationship between circulating neuregulin-1 levels and CCC in stable coronary artery disease patients. Coronary artery disease patients with a stenosis of !90% as evidenced by coronary angiography were included in our study. According to the Rentrop-Cohen classification, coronary collateral degree was graded as 1 to 4. Patients with collateral degree grade 0 or 1 were enrolled in poor CCC group, whereas patients with grade 2 or 3 were enrolled in good CCC group. Plasma neuregulin-1 level was significantly increased in good collateral group and positively related to Rentrop grade (P < 0.01). Multivariate regression analysis and ROC (receiver operating characteristic curve) revealed that plasma neuregulin-1 could predict CCC status effectively. Increased plasma neuregulin-1 level was related to better CCC in patients with coronary artery disease. Neuregulin-1 was an independent and reliable predictor for good coronary collateral development and provided a potential therapeutic strategy to reduce myocardial ischemia injury.

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Expression and secretion of neuregulin-1 in cardiac microvascular endothelial cells treated with angiogenic factors

Cited by 15 publications

References 23 publications

Circulating neuregulin1‐β in heart failure with preserved and reduced left ventricular ejection fraction

Circulating neuregulin1‐β in heart failure with preserved and reduced left ventricular ejection fraction

Association between serum HER2/ErbB2 levels and coronary artery disease: a case–control study

The Relationship Between Circulating Neuregulin-1 and Coronary Collateral Circulation in Patients with Coronary Artery Disease

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