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Bone Morphogenetic Protein-4 Promotes Phenotypic Modulation via SMAD-4/MCT-4 Axis in Vascular Smooth Muscle Cells. 骨形态发生蛋白-4 通过 SMAD-4/MCT-4 轴促进血管平滑肌细胞的表型调节
IF 1.8 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-01-01 Epub Date: 2023-12-27 DOI: 10.1159/000532029
Qi Li, Zhongsha Li, Jingyu Li, Xiaoling Qin, Fengjiao Wu, Chang Chen

Introduction: This study aimed to determine whether bone morphogenetic protein-4 (BMP-4), which increases in response to intimal hyperplasia, promotes phenotype transition in vascular smooth muscle cells (VSMCs).

Methods: Balloon injury was used to induce intimal hyperplasia in rats. Hematoxylin-eosin staining was used to detect the alteration of vascular structure. Serum levels of BMP-4 and lactate were detected by ELISA. Human aortic smooth muscle cells (HA-SMCs) were cultured. Protein and mRNA expression levels were detected through Western blot and real-time PCR. Cell migration was measured by transwell assay.

Results: Our data showed that serum concentration of BMP-4 was upregulated after balloon injury. Treatment with BMP-4 inhibitor DMH1 (4-(6-(4-isopropoxyphenyl)pyrazolo(1,5-a)pyrimidin-3-yl)quinoline) suppressed the abnormal expression of BMP-4 and inhibited the intimal hyperplasia induced by balloon injury. Compared to BMP-4-negative medium, BMP-4-positive medium was associated with higher synthetic VSMC marker expression levels and lower in contractile gene markers in cultured HA-SMCs. Transfection of monocarboxylic acid transporters-4 (MCT-4) siRNA inhibited the excretion of lactate induced by BMP-4.

Conclusion: Our analyses provided evidence that BMP-4 and its regulator Smad-4 are key regulators in MCT-4-mediated lactate excretion. This indicates that BMP-4 stimulates the phenotypic transition of VSMCs via SMAD-4/MCT-4 signaling pathway.

简介:本研究旨在确定骨形态发生蛋白-4(BMP-4)是否会促进血管平滑肌细胞(VSMCs)的表型转换:方法:用球囊损伤诱导大鼠血管内膜增生。方法:利用球囊损伤诱导大鼠血管内膜增生,采用苏木精-伊红染色法检测血管结构的改变。通过 ELISA 检测血清中 BMP-4 和乳酸的水平。培养人主动脉平滑肌细胞(HA-SMCs)。通过 Western 印迹和实时 PCR 检测蛋白质和 mRNA 表达水平。结果:结果:我们的数据显示,球囊损伤后血清中的 BMP-4 浓度上调。用 BMP-4 抑制剂 DMH1(4-(6-(4-异丙氧基苯基)吡唑并(1,5-a)嘧啶-3-基)喹啉)治疗可抑制 BMP-4 的异常表达,并抑制球囊损伤诱导的内膜增生。与 BMP-4 阴性培养基相比,BMP-4 阳性培养基与培养 HA-SMC 的合成 VSMC 标记表达水平较高和收缩基因标记表达水平较低有关。转染单羧酸转运体-4(MCT-4)siRNA 可抑制 BMP-4 诱导的乳酸排泄:我们的分析提供了证据,证明BMP-4及其调节因子Smad-4是MCT-4介导的乳酸排泄的关键调节因子。这表明 BMP-4 通过 SMAD-4/MCT-4 信号通路刺激 VSMC 的表型转换。
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引用次数: 0
Contents, Vol. 61, 2024. 目录,第61卷,2024年。
IF 1.8 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-01-01 Epub Date: 2024-12-16 DOI: 10.1159/000542642
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引用次数: 0
Retraction Statement. 撤回声明。
IF 1.8 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-01-01 Epub Date: 2024-07-19 DOI: 10.1159/000540333
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引用次数: 0
Preoperative Congestive Heart Failure Is Associated with Higher 30-Day Myocardial Infarction and Pneumonia after Endovascular Repair of Abdominal Aortic Aneurysm. 腹主动脉瘤血管内修复术后 30 天心肌梗死和肺炎发生率较高与术前充血性心力衰竭有关。
IF 1.8 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-01-01 Epub Date: 2024-09-19 DOI: 10.1159/000540918
Renxi Li, Anton Sidawy, Bao-Ngoc Nguyen

Introduction: Preoperative congestive heart failure (CHF) is associated with higher postoperative mortality and complications in noncardiac surgery. However, postoperative outcomes for patients with preoperative CHF undergoing endovascular aneurysm repair (EVAR) have not been thoroughly established. This study evaluated the effect of preoperative CHF on 30-day outcomes following nonemergent intact EVAR using a large-scale national registry.

Methods: Patients who had infrarenal EVAR were identified in the ACS-NSQIP database from 2012 to 2022. A 1:5 propensity-score matching was used to match demographics, baseline characteristics, aneurysm diameter, distant aneurysm extent, anesthesia, and concomitant procedures between patients with and without preoperative CHF. Thirty-day postoperative outcomes were examined.

Results: 467 (2.84%) CHF patients underwent intact EVAR. Meanwhile, 15,996 non-CHF patients underwent EVAR, where 2,248 of them were matched to all CHF patients. Patients with and without preoperative CHF had comparable 30-day mortality (3.02% vs. 2.62%, p = 0.64). However, CHF patients had higher myocardial infarction (3.02% vs. 1.47%, p = 0.03), pneumonia (3.23% vs. 1.73%, p = 0.04), 30-day readmission (p = 0.01), and longer length of stay (p < 0.01).

Conclusion: While patients with and without preoperative CHF had comparable 30-day mortality rates, those with CHF faced higher risks of cardiopulmonary complications. Effective management of preoperative CHF may help prevent postoperative complications in these patients.

导言:在非心脏手术中,术前充血性心力衰竭(CHF)与较高的术后死亡率和并发症有关。然而,对于术前患有充血性心力衰竭并接受血管内动脉瘤修补术(EVAR)的患者,其术后效果尚未完全确定。本研究通过大规模的全国登记,评估了术前CHF对非急诊完整EVAR术后30天预后的影响:方法:2012 年至 2022 年期间,在 ACS-NSQIP 数据库中识别了肾下 EVAR 患者。采用1:5倾向得分匹配法对术前有和没有CHF的患者进行人口统计学、基线特征、动脉瘤直径、远处动脉瘤范围、麻醉和伴随手术的匹配。对术后30天的结果进行了研究:467名(2.84%)CHF患者接受了完整的EVAR手术。同时,15996 名非慢性阻塞性肺病患者接受了 EVAR,其中 2248 人与所有慢性阻塞性肺病患者匹配。术前患有和不患有慢性阻塞性肺病的患者的 30 天死亡率相当(3.02% 对 2.62%,P = 0.64)。然而,CHF患者的心肌梗死(3.02% vs. 1.47%,p = 0.03)、肺炎(3.23% vs. 1.73%,p = 0.04)、30天再入院(p = 0.01)和住院时间(p < 0.01)均较高:结论:虽然术前患有和未患有心血管疾病的患者的 30 天死亡率相当,但患有心血管疾病的患者面临的心肺并发症风险更高。有效控制术前合并心房颤动有助于预防这些患者的术后并发症。
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引用次数: 0
Relationship of Warfarin and Apixaban with Vascular Function in Patients with Atrial Fibrillation. 华法林和阿哌沙班与心房颤动患者血管功能的关系
IF 1.7 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-01-01 Epub Date: 2024-03-06 DOI: 10.1159/000535618
Rehan T Junejo, Dhiraj Gupta, Richard L Snowdon, Gregory Y H Lip, James P Fisher

Introduction: Atrial fibrillation (AF) is associated with endothelial damage/dysfunction. Herein, we tested the hypothesis that brachial artery flow-mediated dilation (FMD) is superior in AF patients taking apixaban compared to warfarin.

Methods: AF patients on apixaban (n = 46; 67 [7] years; mean [standard deviation]; 15 women) and warfarin (n = 27; 73 [9] years (p < 0.01); 11 women) were recruited. Duplex Doppler ultrasound imaging was undertaken during baseline (2 min), cuff inflation (5 min), and following cuff deflation (3 min). FMD was defined as peak increase in brachial artery diameter following cuff deflation and analysed as percentage change in diameter, as a ratio of FMD, shear rate area under the curve (SRAUC; FMD-to-SRAUC), and using SRAUC as a covariate (FMDSR).

Results: Baseline artery diameter (4.96 [1.14] vs. 4.89 [0.88] mm), peak diameter (5.12 [1.17] vs. 5.14 [0.93] mm), and FMDSR (3.89 [3.62] vs. 4.80 [3.60] %) were not different between warfarin and apixaban (p > 0.05; analysis of covariance with age, CHA2DS2-VASc, years since AF diagnosis, number of diabetics, alcohol drinkers, and units of alcohol consumed per week as covariates). Stepwise multiple regression identified independent association of fibrillation, hypertension, and increased age with FMD.

Conclusion: AF patients on warfarin and apixaban exhibit similar endothelium-dependent vasodilation. Increased blood pressure negatively impacts vasodilator capacity in AF patients.

导言:心房颤动(房颤)与内皮损伤/功能障碍有关。在此,我们测试了服用阿哌沙班的房颤患者肱动脉血流介导的扩张(FMD)优于华法林的假设:招募了服用阿哌沙班(n = 46;67 [7]岁;平均[标准差];15 名女性)和华法林(n = 27;73 [9]岁(p < 0.01);11 名女性)的房颤患者。在基线(2 分钟)、袖带充气(5 分钟)和袖带放气(3 分钟)期间进行了双相多普勒超声成像。FMD 被定义为袖带放气后肱动脉直径的峰值增加,并以直径变化的百分比、FMD 与剪切率曲线下面积(SRAUC;FMD-to-SRAUC)之比以及将 SRAUC 作为协变量(FMDSR)进行分析:结果:华法林和阿哌沙班的基线动脉直径(4.96 [1.14] vs. 4.89 [0.88] mm)、峰值直径(5.12 [1.17] vs. 5.14 [0.93] mm)和 FMDSR(3.89 [3.62] vs. 4.80 [3.60] %)没有差异(p > 0.05;以年龄、CHA2DS2-VASc、确诊房颤以来的年数、糖尿病患者人数、饮酒者和每周饮酒单位为协变量进行协方差分析)。逐步多元回归确定了心颤、高血压和年龄增加与 FMD 的独立关联:结论:服用华法林和阿哌沙班的房颤患者表现出相似的内皮依赖性血管扩张。血压升高会对房颤患者的血管舒张能力产生负面影响。
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引用次数: 0
Perivascular Adipose Tissue Remodels Only after Elevation of Blood Pressure in the Dahl SS Rat Fed a High-Fat Diet. 以高脂肪饮食喂养的 Dahl SS 大鼠只有在血压升高后血管周围脂肪组织才会发生重塑。
IF 1.7 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-01-01 Epub Date: 2023-12-19 DOI: 10.1159/000535513
Caitlin Wilson, Janice M Thompson, Leah Terrian, Adam D Lauver, Emma D Flood, Gregory D Fink, Lisa Sather, Sudin Bhattacharya, G Andres Contreras, Stephanie W Watts

Introduction: Tunica media extracellular matrix (ECM) remodeling is well understood to occur in response to elevated blood pressure, unlike the remodeling of other tunicas. We hypothesize that perivascular adipose tissue (PVAT) is responsive to hypertension and remodels as a protective measure.

Methods: The adventitia and PVAT of the thoracic aorta were used in measuring ECM genes from 5 pairs of Dahl SS male rats on 8 or 24 weeks of feeding from weaning on a control (10% Kcal fat) or high-fat (HF; 60%) diet. A PCR array of ECM genes was performed with cDNA from adventitia and PVAT after 8 and 24 weeks. A gene regulatory network of the differentially expressed genes (DEGs) (HF 2-fold > con) was created using Cytoscape.

Results: After 8 weeks, 29 adventitia but 0 PVAT DEGs were found. By contrast, at 24 weeks, PVAT possessed 47 DEGs while adventitia had 3. Top DEGs at 8 weeks in adventitia were thrombospondin 1 and collagen 8a1. At 24 weeks, thrombospondin 1 was also a top DEG in PVAT. The transcription factor Adarb1 was identified as a regulator of DEGs in 8-week adventitia and 24-week PVAT.

Conclusion: These data support that PVAT responds biologically once blood pressure is elevated.

简介中膜细胞外基质(ECM)重塑是对血压升高的反应,与其他中膜的重塑不同。我们假设血管周围脂肪组织(PVAT)对高血压有反应并重塑作为一种保护措施:方法:用 5 对 Dahl SS 雄性大鼠的胸主动脉临膜和 PVAT 测量 ECM 基因,这 5 对大鼠从断奶起以对照组(10% 千卡脂肪)或高脂肪(HF;60%)饮食喂养 8 或 24 周。在 8 周和 24 周后,用来自血管内膜和 PVAT 的 cDNA 对 ECM 基因进行了 PCR 阵列分析。使用 Cytoscape 创建了差异表达基因(DEGs)(HF 2 倍 > con)的基因调控网络:结果:8 周后,发现了 29 个临近组织 DEGs,但 PVAT DEGs 为 0。相比之下,在 24 周时,PVAT 有 47 个 DEGs,而血管壁有 3 个。8 周时,临近组织中最主要的 DEGs 是血栓软骨素 1 和胶原 8a1。在24周时,血栓软骨素1也是PVAT的最高DEG。转录因子 Adarb1 被确定为 8 周临近组织和 24 周 PVAT 中 DEGs 的调节因子:这些数据支持一旦血压升高,PVAT 就会做出生物反应。
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引用次数: 0
Assessment for Carotid Atherosclerotic Plaque Using Vessel Wall Magnetic Resonance Imaging: A Multireader ROC Study to Determine Optimal Sequence for Detecting Vessel Wall Calcification. 使用血管壁磁共振成像评估颈动脉粥样硬化斑块:确定检测血管壁钙化最佳序列的多机 ROC 研究。
IF 1.7 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-01-01 Epub Date: 2024-03-28 DOI: 10.1159/000538175
Hideki Ishimaru, Yohei Ikebe, Tsuyoshi Izumo, Hiroshi Imai, Minoru Morikawa, Reiko Ideguchi, Ayano Ishiyama, Hirofumi Koike, Masataka Uetani, Ryo Toya

Introduction: We aimed to compare conventional vessel wall MR imaging techniques and quantitative susceptibility mapping (QSM) to determine the optimal sequence for detecting carotid artery calcification.

Methods: Twenty-two patients who underwent carotid vessel wall MR imaging and neck CT were enrolled. Four slices of 6-mm sections from the bilateral internal carotid bifurcation were subdivided into 4 segments according to clock position (0-3, 3-6, 6-9, and 9-12) and assessed for calcification. Two blinded radiologists independently reviewed a total of 704 segments and scored the likelihood of calcification using a 5-point scale on spin-echo imaging, FLASH, and QSM. The observer performance for detecting calcification was evaluated by a multireader, multiple-case receiver operating characteristic study. Weighted κ statistics were calculated to assess interobserver agreement.

Results: QSM had a mean area under the receiver operating characteristic curve of 0.85, which was significantly higher than that of any other sequence (p < 0.01) and showed substantial interreader agreement (κ = 0.68). A segment with a score of 3-5 was defined as positive, and a segment with a score of 1-2 was defined as negative; the sensitivity and specificity of QSM were 0.75 and 0.87, respectively.

Conclusion: QSM was the most reliable MR sequence for the detection of plaque calcification.

简介:我们的目的是比较传统血管壁磁共振成像技术和定量易感性绘图(QSM):我们旨在比较传统的血管壁磁共振成像技术和定量易感性图谱(QSM),以确定检测颈动脉钙化的最佳序列:22名患者接受了颈动脉血管壁磁共振成像和颈部CT检查。根据时钟位置(0-3、3-6、6-9 和 9-12)将双侧颈内动脉分叉处的四张 6 毫米切片细分为 4 个区段,并评估钙化情况。两名盲放射科医生独立检查了总共 704 个节段,并使用自旋回波成像、FLASH 和 QSM 的 5 点评分法对钙化的可能性进行评分。通过多阅读器、多病例接收器操作特征研究评估了观察者检测钙化的性能。计算加权κ统计量以评估观察者之间的一致性:QSM的接收器操作特征曲线下的平均面积为0.85,明显高于其他序列(p <0.01),并显示出很大的读片者间一致性(κ = 0.68)。得分 3-5 的区段被定义为阳性,得分 1-2 的区段被定义为阴性;QSM 的敏感性和特异性分别为 0.75 和 0.87:结论:QSM 是检测斑块钙化最可靠的 MR 序列。
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引用次数: 0
In Memoriam: A Tribute to Eva Aralikatti. 悼念向伊娃-阿拉里卡蒂致敬。
IF 1.8 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-01-01 Epub Date: 2024-08-30 DOI: 10.1159/000540829
Pooneh Bagher
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引用次数: 0
Cytoprotection as an Innovative Therapeutic Strategy to Cardiogenic Shock: Exploring the Potential of Cytidine-5-Diphosphocholine to Mitigate Target Organ Damage. 细胞保护作为心源性休克的创新治疗策略:探索胞苷-5-二磷酸胆碱减轻靶器官损伤的潜力。
IF 1.8 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-01-01 Epub Date: 2024-05-22 DOI: 10.1159/000538946
Héctor González-Pacheco, Luis Manuel Amezcua-Guerra, Martha Franco, Alexandra Arias-Mendoza, Jorge A Ortega-Hernández, Felipe Massó

Background: Preservation of organ function and viability is a crucial factor for survival in cardiogenic shock (CS) patients. There is not information enough on cytoprotective substances that may delay organs damage in CS. We hypothesize that cytidine-5-diphosphocholine (CDP-choline) can act as a cytoprotective pharmacological measure that diminishes the target organ damage. So, we aimed to perform a review of works carried out in our institution to evaluate the effect of therapeutic cytoprotection of the CDP-choline.

Summary: CDP-choline is an intermediate metabolite in the synthesis of phosphatidylcholine. It is also a useful drug for the treatment of acute ischaemic stroke, traumatic brain injury, and neurodegenerative diseases and has shown an excellent pharmacological safety profile as well. We review our institution's work and described the cytoprotective effects of CDP-choline in experimental models of heart, liver, and kidney acute damage, where this compound was shown to diminish reperfusion-induced ventricular arrhythmias, oxidative stress, apoptotic cell death, inflammation, lactic acid levels and to preserve mitochondrial function.

Key messages: We propose that additional research is needed to evaluate the impact of cytoprotective therapy adjuvant to mitigate target organ damage in patients with CS.

背景:保持器官功能和活力是心源性休克(CS)患者存活的关键因素。关于可延缓 CS 中器官损伤的细胞保护物质的信息还不够多。我们假设胞苷-5-二磷酸胆碱(CDP-胆碱)可作为一种细胞保护药理措施,减轻靶器官损伤。因此,我们旨在对本机构开展的工作进行回顾,以评估 CDP 胆碱的细胞保护治疗效果。摘要:CDP 胆碱是合成磷脂酰胆碱的中间代谢产物。它也是治疗急性缺血性中风、创伤性脑损伤和神经退行性疾病的一种有效药物,并显示出极佳的药理安全性。我们回顾了本研究机构的工作,描述了 CDP-choline 在心脏、肝脏和肾脏急性损伤实验模型中的细胞保护作用,结果表明这种化合物能减少再灌注引起的室性心律失常、氧化应激、细胞凋亡、炎症、乳酸水平,并能保护线粒体功能:我们建议需要开展更多研究,以评估细胞保护疗法辅助减轻 CS 患者靶器官损伤的影响。
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引用次数: 0
Endothelial Dysfunction Does Not Occur after Acute, Elevated Homocysteine Exposure of the Lumen of the Iliac Artery of the Anaesthetised Pig. 麻醉猪髂动脉腔内同型半胱氨酸急性升高后不会出现内皮功能障碍
IF 1.8 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Pub Date : 2024-01-01 Epub Date: 2024-10-09 DOI: 10.1159/000541398
Farouk Markos, Andrew J O'Leary, Mark I M Noble, Therese Ruane-O'Hora

Introduction: Elevated luminal homocysteine has been linked with cardiovascular disease; however, whether there is a direct effect of homocysteine on blood vessel endothelium is not clear. In this study, the acute effect of luminal homocysteine on iliac artery endothelial function was assessed in the anaesthetised pig.

Methods: Hyperhomocysteinaemic blood was injected into an occluded segment of the iliac in the anaesthetised pig for 20 min, and the effect on atrial diameter during the occlusion and during the reactive hyperaemia assessed.

Results: No significant changes in arterial diameter or pressure were observed during the incubation period at homocysteine concentrations of 10, 20, 40 and 100 µM. There was also no difference in the magnitude of the iliac diameter increase in the response to reactive hyperaemia when the incubation period was completed.

Conclusion: There is no evidence of endothelial dysfunction in response to an acute 20-min elevation in homocysteine in an intact conduit artery.

导言:管腔同型半胱氨酸升高与心血管疾病有关,但同型半胱氨酸对血管内皮是否有直接影响尚不清楚。本研究评估了管腔同型半胱氨酸对麻醉猪髂动脉内皮功能的急性影响。方法:将高同型半胱氨酸血症血液注入麻醉猪髂动脉闭塞段 20 分钟,评估闭塞期间和反应性高血症期间对心房直径的影响:结果:在同型半胱氨酸浓度为 10、20、40 和 100 µM 的孵育期间,未观察到动脉直径或压力发生明显变化。孵育期结束后,髂骨直径在反应性高血症反应中的增加幅度也没有差异:结论:在完整的导管动脉中,没有证据表明同型半胱氨酸急性升高 20 分钟会导致内皮功能障碍。
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引用次数: 0
期刊
Journal of Vascular Research
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