Circulating extracellular vesicles from patients with valvular heart disease induce neutrophil chemotaxis via FOXO3a and the inhibiting role of dexmedetomidine

Yuan, Hao‐Xiang; Chen, Caiyun; Li, Yuquan; Ning, Da-Sheng; Li, Yan; Chen, Ya-Ting; Li, Shang-Xuan; Fu, Mengxia; Li, Xiaodi; Ma, Jian; Jian, Yutao; Liu, Donghong; Mo, Ziwei; Peng, Yulin; Xu, Kan; Ou, Zhi‐Jun; Ou, Jing‐Song

doi:10.1152/ajpendo.00062.2020

Cited by 14 publications

(13 citation statements)

References 78 publications

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“…HUVECs were cultured with PBS, nHDL (100 μg/mL), dHDL (100 μg/mL or different doses), siRNA, miRNA mimic, miRNA inhibitor, or TNF-α. Cellular proteins were harvested for Western blot analysis as previously described [ [31] , [32] , [33] , 36 , 37 ].…”

Section: Methodsmentioning

confidence: 99%

Angiogenic and Antiangiogenic mechanisms of high density lipoprotein from healthy subjects and coronary artery diseases patients

Peng

et al. 2020

Redox Biology

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Normal high-density lipoprotein (nHDL) in normal, healthy subjects is able to promote angiogenesis, but the mechanism remains incompletely understood. HDL from patients with coronary artery disease may undergo a variety of oxidative modifications, rendering it dysfunctional; whether the angiogenic effect is mitigated by such dysfunctional HDL (dHDL) is unknown. We hypothesized that dHDL compromises angiogenesis. The angiogenic effects of nHDL and dHDL were assessed using endothelial cell culture, endothelial sprouts from cardiac tissue from C57BL/6 mice, zebrafish model for vascular growth and a model of impaired vascular growth in hypercholesterolemic low-density lipoprotein receptor null(LDLr -/- )mice. MiRNA microarray and proteomic analyses were used to determine the mechanisms. Lipid hydroperoxides were greater in dHDL than in nHDL. While nHDL stimulated angiogenesis, dHDL attenuated these responses. Protein and miRNA profiles in endothelial cells differed between nHDL and dHDL treatments. Moreover, nHDL suppressed miR-24-3p expression to increase vinculin expression resulting in nitric oxide (NO) production, whereas dHDL delivered miR-24-3p to inhibit vinculin expression leading to superoxide anion (O 2 •- ) generation via scavenger receptor class B type 1. Vinculin was required for endothelial nitric oxide synthase (eNOS) expression and activation and modulated the PI3K/AKT/eNOS and ERK1/2 signaling pathways to regulate nHDL- and VEGF-induced angiogenesis. Vinculin overexpression or miR-24-3p inhibition reversed dHDL-impaired angiogenesis. The expressions of vinculin and eNOS and angiogenesis were decreased, but the expression of miR-24-3p and lipid hydroperoxides in HDL were increased in the ischemic lower limbs of hypercholesterolemic LDLr -/- mice. Overexpression of vinculin or miR-24-3p antagomir restored the impaired-angiogenesis in ischemic hypercholesterolemic LDLr -/- mice. Collectively, nHDL stimulated vinculin and eNOS expression to increase NO production by suppressing miR-24-3p to induce angiogenesis, whereas dHDL inhibited vinculin and eNOS expression to enhance O 2 •- generation by delivering miR-24-3p to impair angiogenesis, and that vinculin and miR-24-3p may be therapeutic targets for dHDL-impaired angiogenesis.

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Section: Methodsmentioning

confidence: 99%

Angiogenic and Antiangiogenic mechanisms of high density lipoprotein from healthy subjects and coronary artery diseases patients

Peng

et al. 2020

Redox Biology

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“…MPs were isolated from enrolled patients by differential centrifugation as previously reported (5,10,18). According to the methodological guidelines to study MPs (21), intravenous blood was drawn by the vacuum citrateanticoagulant tubes and the first tube was discarded to avoid the influence of blood injury induced by venipuncture.…”

Section: Mps Isolationmentioning

confidence: 99%

“…The platelet-poor plasma was thawed in the water bath at 37 ℃ and kept at room temperature (RT) before detection. The measurement of MPs and its subpopulations was done as previously done by FCM (18). The plasma was incubated with AnnexinV-FITC with binding buffer for 30 min in the dark at RT to stain the total MPs.…”

Section: Flow Cytometry (Fcm)mentioning

confidence: 99%

“…More evidence show that microparticles mediate inflammation, coagulation, oxidative stress injury, and endothelial dysfunction in patients with renal disease and become a promising biomarker of various renal diseases such as thrombotic microangiopathies, nephrotic syndrome, IgA nephropathy, and renal failure (4,15). In view of molecular mechanism, MPs, especially EMP, induce endothelial dysfunction by increasing the release of inflammatory cytokines and reducing nitric oxide (5)(6)(7)(8)(16)(17)(18). Recently, we found that circulating MPs from patients with VHD induce chemokines expression and renal neutrophil chemotaxis, which partly contribute to renal dysfunction (18).…”

Section: Introductionmentioning

confidence: 99%

“…In view of molecular mechanism, MPs, especially EMP, induce endothelial dysfunction by increasing the release of inflammatory cytokines and reducing nitric oxide (5)(6)(7)(8)(16)(17)(18). Recently, we found that circulating MPs from patients with VHD induce chemokines expression and renal neutrophil chemotaxis, which partly contribute to renal dysfunction (18). Recent investigations on the correlation between circulating EMP and renal dysfunction found that EMP are elevated in patients with chronic kidney disease (CKD) or septic patients with AKI (19).…”

Section: Introductionmentioning

confidence: 99%

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Circulating endothelial microparticles: a promising biomarker of acute kidney injury after cardiac surgery with cardiopulmonary bypass

Ma¹,

Yuan²,

Chen³

et al. 2021

Ann Transl Med

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Background: Current diagnostic strategies for acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB) are nonspecific and limited. Previously, we demonstrated that circulating microparticles (MPs) in patients with valve heart disease (VHD) and congenital heart diseases (CHD) induce endothelial dysfunction and neutrophil chemotaxis, which may result in kidney injury. We also found that circulating MPs increase after cardiac surgery with CPB and are related to cardiac function. However, the relationship between circulating MPs and AKI after CPB is unknown.Methods: Eighty-five patients undergoing cardiac surgery with CPB were enrolled. Patients were divided into AKI and non-AKI groups based on the serum creatinine levels at 12 h and 3 d post-CPB. Circulating MPs were isolated from plasma, and their levels including its subtypes were detected by flow cytometer. Independent risk factors for the CPB-associated AKI (CPB-AKI) were determined by multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to measure the prognostic potential of CPB-AKI.Results: The morbidity of AKI at 12 h and 3 d after cardiac surgery with CPB was 40% and 31.76%, respectively. The concentrations of total MPs and platelet-derived MPs (PMP) remained unchanged at 12 h and then increased at 3 d post-CPB, while that of endothelial-derived MPs (EMP) increased at both time points. In patients with AKI, PMP and EMP were elevated compared with the patients without AKI. However, no significant change was detected on monocyte-derived MPs (MMP) at 12 h and 3 d post-CPB.The logistic regression analysis showed that EMP was the independent risk factor for AKI both at 12 h and 3 d post-CPB. The area under ROC for the concentrations of EMP at 12 h and 3 d post-CPB was 0.86 and

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Crosstalk between myofibroblasts and macrophages: A regulative factor of valvular fibrosis in calcific aortic valve disease

Huang

et al. 2022

Cell Biology International

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Inflammation and fibrosis are highly correlated with the progression of calcific aortic valve disease (CAVD). As one of the differentiated forms of valvular interstitial cells, myofibroblasts play a critical role in CAVD's development as do macrophages. Although numerous studies have been conducted on them separately, their communication and interaction remain unclear. We used porcine aortic valves to isolate valve interstitial cells (VICs). VICs were induced to differentiate into myofibroblasts by transforming growth factor‐β1 (TGF‐β1). After successful activation was determined, the myofibroblast‐conditioned medium (CM) was collected and used to act on RAW264.7, a macrophage cell line. A migration and adhesion assay estimated the recruitment capability of myofibroblasts on macrophages. We used flow cytometry, quantitative polymerase chain reaction (qPCR), and Western blot analysis to investigate myofibroblasts' polarity promotion function in macrophages. Finally, we used macrophage‐CM on VICs to explore the differentiation induction function of polarized macrophages. Myofibroblast marker alpha‐smooth muscle actin and M2 macrophage marker CD163 were detected as upregulated in CAVD patients, and their expression has a certain correlation. The Smad3/HA/CD44 axis activated the differentiation of myofibroblasts by Western blot. The myofibroblast‐CM can promote chemotaxis and adhesion of macrophages through protein kinase B/chemokine (C–C motif) ligand5 and Smad3/HA/CD44, respectively. Hyaluronic acid (HA) inside the myofibroblast‐CM stimulates macrophages to polarize into M2 macrophages. In turn, M2 macrophage‐CM has the promotive ability to activate myofibroblasts but fails to induce the osteoblast differentiation of VICs directly. The crosstalk between myofibroblasts and macrophages causes the excessive activation of myofibroblasts. This positive feedback loop may play a vital role in CAVD progression.

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Circulating extracellular vesicles from patients with valvular heart disease induce neutrophil chemotaxis via FOXO3a and the inhibiting role of dexmedetomidine

Cited by 14 publications

References 78 publications

Angiogenic and Antiangiogenic mechanisms of high density lipoprotein from healthy subjects and coronary artery diseases patients

Angiogenic and Antiangiogenic mechanisms of high density lipoprotein from healthy subjects and coronary artery diseases patients

Circulating endothelial microparticles: a promising biomarker of acute kidney injury after cardiac surgery with cardiopulmonary bypass

Crosstalk between myofibroblasts and macrophages: A regulative factor of valvular fibrosis in calcific aortic valve disease

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