Vascular pharmacology最新文献_第3页

Growth differentiation factor 15 protects against diabetic endothelial dysfunction by AMP-activated protein kinase mediation 生长分化因子15通过amp激活的蛋白激酶介导糖尿病内皮功能障碍。

IF 3.5 3区医学 Q2 PHARMACOLOGY & PHARMACY

Vascular pharmacology

Pub Date : 2025-10-21 DOI: 10.1016/j.vph.2025.107554

Wen Zhao , Yang Liu , Zhengshuo Cui , Xinxin Li, Han Guo, Xueying Chen, Huina Zhang

Aims

Endothelial dysfunction is a hallmark of diabetes-associated cardiovascular complications, yet its molecular mechanisms remain incompletely elucidated. Growth differentiation factor 15 (GDF15) has emerged as an important modulator in metabolic and cardiovascular diseases; however, its role in diabetic endothelial dysfunction is poorly understood. This study aims to investigate the therapeutic potential of GDF15 in diabetic endothelial dysfunction and to elucidate the underlying mechanisms.

Methods

db/db mouse aortas or high glucose/high lipid (HG/HL)-treated C57BL/6 mouse aortas were exposed to GDF15 for acute or prolonged durations. Endothelium-dependent relaxation (EDR) was evaluated using wire myography. Meanwhile, western blotting was performed to assess protein levels of nuclear factor erythroid 2-related factor 2 (NRF2), NADPH oxidase 2 (NOX2), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), total AMP-activated protein kinase (AMPK), and phosphorylated AMPK in endothelial cells treated with GDF15 in the presence or absence of HG/HL. Reactive oxygen species (ROS) production in en face endothelial cells of mouse aortas was measured via confocal microscopy.

Results

Exogenous GDF15 acute or prolonged administration markedly ameliorated HG/HL- and diabetes-induced endothelial dysfunction and excess reactive oxygen species (ROS) generation. Meanwhile, GDF15 counteracted HG/HL-induced changes in NOX2, NRF2, ACE, and ACE2 protein expression in endothelial cells. These beneficial effects of GDF15 were mechanistically linked to AMPK upregulation, as evidenced by elevated AMPK levels in GDF15-treated endothelial cells, and the suppression of GDF15's vasoprotective effects by the AMPK inhibitor Compound C.

Conclusions

Our findings demonstrate that GDF15 ameliorates diabetic endothelial dysfunction and oxidative stress by AMPK-dependent pathways in endothelial cells. These results highlight GDF15 as a promising therapeutic target for mitigating oxidative stress and preserving diabetic endothelial dysfunction.

目的：内皮功能障碍是糖尿病相关心血管并发症的一个标志，但其分子机制仍未完全阐明。生长分化因子15 （GDF15）已成为代谢和心血管疾病的重要调节剂；然而，其在糖尿病内皮功能障碍中的作用尚不清楚。本研究旨在探讨GDF15在糖尿病内皮功能障碍中的治疗潜力，并阐明其潜在机制。方法：将db/db小鼠主动脉或HG/HL处理的C57BL/6小鼠主动脉急性或长时间暴露于GDF15。内皮依赖性松弛（EDR）采用钢丝肌图评估。同时，采用western blotting检测在HG/HL存在或不存在的情况下，GDF15处理的内皮细胞中核因子-红细胞2相关因子2 （NRF2）、NADPH氧化酶2 （NOX2）、血管紧张素转换酶（ACE）、血管紧张素转换酶2 （ACE2）、总amp活化蛋白激酶（AMPK）和磷酸化AMPK的蛋白水平。用共聚焦显微镜观察小鼠主动脉表面内皮细胞活性氧（ROS）的产生。结果：外源性GDF15急性或长期给药可显著改善HG/HL和糖尿病诱导的内皮功能障碍和过量活性氧（ROS）的产生。同时，GDF15可以抵消HG/ hl诱导的内皮细胞中NOX2、NRF2、ACE和ACE2蛋白表达的变化。GDF15的这些有益作用在机制上与AMPK上调有关，如GDF15处理的内皮细胞中AMPK水平升高，以及AMPK抑制剂化合物c抑制GDF15的血管保护作用。结论：我们的研究结果表明，GDF15通过内皮细胞中AMPK依赖的途径改善了糖尿病内皮功能障碍和氧化应激。这些结果突出了GDF15作为减轻氧化应激和保护糖尿病内皮功能障碍的有希望的治疗靶点。

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引用次数: 0

Pre-eclampsia with inflammatory and pro-resolving mediator fluctuations - contributions from hemolytic protozoan parasites 伴有炎症和促溶解介质波动的先兆子痫——溶血性原生动物寄生虫的贡献。

IF 3.5 3区医学 Q2 PHARMACOLOGY & PHARMACY

Vascular pharmacology

Pub Date : 2025-10-14 DOI: 10.1016/j.vph.2025.107552

Kevin Roe

Pre-eclampsia (PE) and eclampsia are inflammatory hypertension diseases which have globally caused countless millions of fatalities among pregnant women, and their pathogenesis has been a centuries-long mystery. Substantial experimental evidence, including extensive cytokine signatures, symptoms, characteristics and drug interactions, suggest initiation by hemolytic protozoan parasite infections which provide heme and iron for reactivation of iron-deprived bacterial and/or viral infections. However, there are unexplained PE and eclampsia secondary characteristics: (1) Why are endothelial dysfunction and vascular inflammation ubiquitous in pregnancies complicated by PE and eclampsia? (2) Why does pregnancy termination resolve the inflammation of pregnancies complicated by PE and eclampsia? (3) Why do omega-3 polyunsaturated fatty acids, including DHA and EFA and their derived resolvins, have decreased blood levels, whereas omega-6 polyunsaturated fatty acids have elevated levels? (4) Why is low-dose aspirin therapy frequently effective in preventing PE and eclampsia? There are now plausible explanations for these secondary characteristics. These explanations also support the hypothesis that PE and eclampsia are diseases induced by bacterial or viral infections concurrent with an almost asymptomatic strain of hemolytic protozoan parasite infection providing a virulence boost, with the reactivated infections inducing chronic inflammation. This also causes abnormal fluctuations in special pro-resolving mediators, including lipoxins, resolvins, protectins and maresins, which would normally participate in resolving acute inflammations.

子痫前期（PE）和子痫是一种炎症性高血压疾病，在全球造成数百万孕妇死亡，其发病机制一直是一个长达几个世纪的谜。大量实验证据，包括广泛的细胞因子特征、症状、特征和药物相互作用，表明由溶血性原虫寄生虫感染引发，这些寄生虫感染为缺铁细菌和/或病毒感染的再激活提供血红素和铁。然而，PE和子痫的继发特征无法解释：(1)为什么PE和子痫合并妊娠中内皮功能障碍和血管炎症普遍存在？(2)为什么终止妊娠可以解决妊娠合并PE和子痫的炎症？(3)为什么omega-3多不饱和脂肪酸（包括DHA和EFA及其衍生的分解素）的血液水平降低，而omega-6多不饱和脂肪酸的血液水平升高？(4)为什么小剂量阿司匹林在预防PE和子痫中经常有效？现在对这些次要特征有了合理的解释。这些解释也支持了PE和子痫是由细菌或病毒感染并发溶血性原虫寄生虫感染引起的疾病，再激活感染诱导慢性炎症的假设。这也会导致一些特殊的促溶解介质的异常波动，包括脂毒素、溶解蛋白、保护蛋白和蛋白酶，这些介质通常会参与急性炎症的溶解。

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引用次数: 0

Hypothalamic regulation of obesity: Revealing the therapeutic potential of a novel anti-obesity peptide 下丘脑调节肥胖：揭示一种新型抗肥胖肽的治疗潜力。

IF 3.5 3区医学 Q2 PHARMACOLOGY & PHARMACY

Vascular pharmacology

Pub Date : 2025-10-13 DOI: 10.1016/j.vph.2025.107553

Yi Ning Choo , Ram Narayanan , Vetriselvan Subramaniyan

Obesity is a chronic, complex condition defined by excessive fat buildup due to an imbalance between caloric consumption and energy expenditure. The significant global rise in prevalence of obesity is associated with numerous comorbidities, such as cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. Conventional management approaches, including diet, exercise, pharmacotherapy, and bariatric surgery, may demonstrate restricted long-term effectiveness owing to inadequate adherence and physiological adjustments. Recent advancements in neuroscience underscore the hypothalamus as a pivotal regulator of energy balance via essential nuclei, including the arcuate nucleus (ARC), paraventricular nucleus (PVN), lateral hypothalamic area (LHA), and ventromedial nucleus (VMN). This review examines the therapeutic potential of a new anti-obesity peptide that targets hypothalamic signalling pathways. Preclinical and clinical evidence endorses the utilization of glucagon-like peptide-1 receptor (GLP-1R) agonists and novel multi-receptor drugs such as AMG 133, which integrate GLP-1R activation with glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonism. These therapies exhibit improved weight reduction and metabolic enhancement. Moreover, the integration of hypothalamic peptide therapy with lifestyle modifications or post-bariatric care provides synergistic advantages. Notwithstanding favorable results, peptide therapy encounters obstacles such as administration methods, sustained effectiveness, and expense. Overcoming these obstacles is crucial for the effective implementation of peptide-based treatments in sustained clinical obesity control.

肥胖是一种慢性、复杂的疾病，由热量消耗和能量消耗之间的不平衡导致的过度脂肪堆积所定义。全球肥胖患病率的显著上升与许多合并症有关，如心血管疾病、2型糖尿病和非酒精性脂肪性肝病。传统的管理方法，包括饮食、运动、药物治疗和减肥手术，由于不充分的坚持和生理调整，可能显示出有限的长期有效性。神经科学的最新进展强调下丘脑作为能量平衡的关键调节器，通过必要的核，包括弓状核（ARC）、室旁核（PVN）、下丘脑外侧区（LHA）和腹内侧核（VMN）。本文综述了一种针对下丘脑信号通路的新型抗肥胖肽的治疗潜力。临床前和临床证据支持使用胰高血糖素样肽-1受体（GLP-1R）激动剂和新型多受体药物，如AMG 133，将GLP-1R激活与葡萄糖依赖性胰岛素性多肽受体（GIPR）拮抗结合起来。这些疗法表现出减轻体重和促进代谢的效果。此外，下丘脑肽治疗与生活方式改变或减肥后护理的整合提供了协同优势。尽管有良好的结果，肽治疗遇到障碍，如给药方法，持续有效性和费用。克服这些障碍对于有效实施持续临床肥胖控制的肽类治疗至关重要。

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引用次数: 0

The endothelium at the crossroads of multi-organ pathology: Insights from organ-on-chip models 内皮在多器官病理的十字路口：从器官芯片模型的见解。

IF 3.5 3区医学 Q2 PHARMACOLOGY & PHARMACY

Vascular pharmacology

Pub Date : 2025-10-10 DOI: 10.1016/j.vph.2025.107551

Swachhatoa Ghosh, Praphulla C. Shukla, Soumen Das

Endothelial barrier function is indispensable in maintaining vascular-tissue-organ homeostasis. Altered release of vasoactive substances along with fluctuating shear stress patterns result in an impaired barrier function leading to transmigration of blood components, tumor infiltrates and pathogens. Organ-on-chip (OoC) technology leverage microfabrication techniques to develop dynamic, three-dimensional (3D) in vitro platforms that closely mimic the structural and functional characteristics of human tissues, including the vasculature. These systems offer powerful tools for modeling disease mechanisms with high physiological relevance and are increasingly utilized in drug development, diagnostics, and therapeutic screening. By integrating biomimetic vascular environments, OoC platforms allow for the investigation of how endothelial barrier disruption, inflammatory signaling, and mechanical cues contribute to pathophysiology. Importantly, since endothelial dysfunction often precedes clinical symptoms, these models offer promising avenues for early disease detection and intervention. Together, these approaches provide a roadmap for using organ-on-chip systems to dissect vascular contributions to disease and to improve predictive, human-relevant preclinical models.

内皮屏障功能在维持血管-组织-器官稳态中是不可或缺的。血管活性物质释放的改变伴随着剪切应力模式的波动，导致屏障功能受损，导致血液成分、肿瘤浸润物和病原体的迁移。器官芯片（OoC）技术利用微加工技术开发动态的三维（3D）体外平台，密切模仿人体组织的结构和功能特征，包括脉管系统。这些系统为具有高度生理相关性的疾病机制建模提供了强大的工具，并越来越多地用于药物开发、诊断和治疗筛选。通过整合仿生血管环境，OoC平台允许研究内皮屏障破坏、炎症信号和机械线索如何促进病理生理学。重要的是，由于内皮功能障碍通常先于临床症状，这些模型为早期疾病检测和干预提供了有希望的途径。总之，这些方法为使用器官芯片系统解剖血管对疾病的贡献和改进预测性的、与人类相关的临床前模型提供了路线图。

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引用次数: 0

Efficacy and safety of lorundrostat in patients with uncontrolled or resistant hypertension: A systematic review and meta-analysis with trial sequential analysis lorundrostat在不受控制或顽固性高血压患者中的疗效和安全性：一项系统评价和荟萃分析与试验序贯分析。

IF 3.5 3区医学 Q2 PHARMACOLOGY & PHARMACY

Vascular pharmacology

Pub Date : 2025-10-09 DOI: 10.1016/j.vph.2025.107550

Laila Shalabi , Abdelrahman M. Tawfik , Bashar M. Al Zoubi , Ahmad Al Othman , Sofian Zreigh , Mohamed Abuelazm

Background

Uncontrolled hypertension (HTN) remains a challenge despite multiple anti-hypertensive medications. This study systematically evaluates the efficacy and safety of Lorundrostat, a novel aldosterone synthase inhibitor, in patients with uncontrolled hypertension.

Methods

A comprehensive search of major electronic databases was conducted until Jul 14, 2025, to identify randomized controlled trials (RCTs) comparing Lorundrostat with placebo. The primary outcomes included changes in office systolic and diastolic blood pressure (BP). A random-effects model was used to pool the data, presented as risk ratios (RR) or mean differences (MD) with 95 % confidence intervals (CIs).

Results

The pooled analysis of three RCTs comprising 1562 patients demonstrated that lorundrostat yielded statistically significant reductions in both office systolic BP (MD = −8.26 mmHg; 95 % CI: −10.87 to −5.64; p < 0.0001) and diastolic BP (MD = −3.53 mmHg; 95 % CI: −5.62 to −1.43; p = 0.001). However, Lorundrostat was associated with increased risks of hyperkalemia (RR = 7.93; 95 % CI: 1.55 to 40.64; p = 0.0131), hyponatremia (RR = 1.96; 95 % CI: 1.15 to 3.35; p = 0.0133), hypotension (RR = 3.06; 95 % CI: 1.15 to 8.11; p = 0.0250), and any adverse events (RR = 1.47; 95 % CI: 1.29 to 1.67; p < 0.0001).

Conclusion

Lorundrostat effectively controls blood pressure in patients with uncontrolled hypertension; however, it also increases the incidence of adverse events, and further large-scale trials are needed to confirm long-term efficacy and safety.

PROSPERO ID: CRD420251107424.

背景：尽管有多种抗高血压药物，但不受控制的高血压（HTN）仍然是一个挑战。本研究系统评价了Lorundrostat（一种新型醛固酮合成酶抑制剂）在未控制的高血压患者中的疗效和安全性。方法：到2025年7月14日，对主要电子数据库进行全面检索，以确定Lorundrostat与安慰剂的随机对照试验（rct）。主要结局包括办公室收缩压和舒张压（BP）的变化。随机效应模型用于汇总数据，以95% %置信区间（ci）的风险比（RR）或平均差异（MD）表示。结果：共纳入1562例患者的3项随机对照试验的汇总分析显示，lorundrostat可显著降低两组患者的有效收缩压（MD = -8.26 mmHg; 95% % CI: -10.87 ~ -5.64; p ）结论：lorundrostat可有效控制高血压患者的血压，但也增加了不良事件的发生率，需要进一步的大规模试验来证实其长期疗效和安全性。普洛斯彼罗id: CRD420251107424。

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引用次数: 0

Transcellular permeability of arterial endothelium to plasma LDL, an underexplored target in treating atherosclerosis: Novel insights and potential treatment strategies 动脉内皮对血浆LDL的跨细胞渗透性，是治疗动脉粥样硬化的一个未被充分探索的靶点：新的见解和潜在的治疗策略

IF 3.5 3区医学 Q2 PHARMACOLOGY & PHARMACY

Vascular pharmacology

Pub Date : 2025-10-02 DOI: 10.1016/j.vph.2025.107549

Israel O. Bolanle, Gaetan de Liedekerke Beaufort

Ischaemic heart disease, of which atherosclerosis is the primary substrate, continues to be a leading cause of death globally. Atherosclerosis is characterised by the accumulation of cholesterol, mainly from circulating low-density lipoprotein (LDL), within the arterial wall. LDL influx is determined by the product of two variables: the concentration of LDL in plasma and the permeability of the endothelium to LDL. Lowering the former is the primary therapeutic strategy employed today. Meanwhile, lowering permeability ought to be equally beneficial, and its effect on influx would likely be multiplicative with lipid lowering, but it is currently underexplored as a target in treating atherosclerosis. Advances in electron microscopy have helped improve our understanding of the three primary routes through which LDL permeates the endothelium: transcellular (via passive and active, receptor-mediated transport that involves the movement of LDL as cargo inside caveolae), paracellular (via interendothelial/paracellular junctions), and through cells undergoing mitosis and apoptosis (leaky junctions). We have therefore highlighted in this review, based on recent advances in experimental and translational investigations viable pharmacological agents that modulate transendothelial permeability to LDL as potential treatment options for atherosclerosis.

缺血性心脏病，其中动脉粥样硬化是主要底物，仍然是全球死亡的主要原因。动脉粥样硬化的特征是胆固醇的积累，主要来自动脉壁内循环的低密度脂蛋白（LDL）。LDL内流是由两个变量的乘积决定的：血浆中LDL的浓度和内皮对LDL的渗透性。降低前者是目前采用的主要治疗策略。同时，降低通透性应该同样有益，其对内流的影响可能与降脂作用倍增，但目前尚未充分探索其作为治疗动脉粥样硬化的靶点。电子显微镜技术的进步有助于提高我们对低密度脂蛋白渗透内皮的三种主要途径的理解：跨细胞（通过被动和主动，受体介导的运输，包括LDL作为货物在小泡内的运动），细胞旁（通过内皮间/细胞旁连接），以及通过细胞进行有丝分裂和凋亡（漏接）。因此，基于实验和转化研究的最新进展，我们在这篇综述中强调了调节经内皮细胞对LDL的渗透性的可行药物作为动脉粥样硬化的潜在治疗选择。

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引用次数: 0

Apelin in glioblastoma: A dual target for tumor and vascular intervention 胶质母细胞瘤中的Apelin：肿瘤和血管干预的双重靶点。

IF 3.5 3区医学 Q2 PHARMACOLOGY & PHARMACY

Vascular pharmacology

Pub Date : 2025-09-30 DOI: 10.1016/j.vph.2025.107548

Gabriela E. Wachholz , Karlijn van Loon , Arjan W. Griffioen

Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults, marked by rapid progression, profound intratumoral heterogeneity and poor prognosis despite multimodal therapy. Current standard-of-care treatments, including maximal surgical resection followed by radiotherapy and temozolomide chemotherapy, offer only modest survival benefits, with most patients facing inevitable recurrence. A defining feature of GBM is its pronounced vascular proliferation, which supports tumor progression. This has spurred interest in targeting angiogenesis as a potential treatment approach. Apelin, a peptide involved in the regulation of angiogenesis and endothelial cell proliferation, has emerged as a key player in GBM pathogenesis. The Apelin/APJ signaling pathway is implicated in promoting tumor vascularization, invasiveness, and resistance to therapy, making it a promising therapeutic target. This review explores the role of Apelin/APJ pathway in GBM progression, focusing on its contribution to angiogenesis, as well as tumor growth and invasiveness. By integrating current findings, we aim to establish the rationale for targeting Apelin signaling as a novel therapeutic strategy in GBM, with the ultimate goal of overcoming treatment resistance and improving patient outcomes.

胶质母细胞瘤（GBM）是成人中最常见和最致命的原发性脑肿瘤，其特点是进展迅速，肿瘤内异质性严重，尽管采用多种治疗方法，预后仍差。目前的标准治疗，包括最大限度的手术切除，放疗和替莫唑胺化疗，只能提供适度的生存益处，大多数患者面临不可避免的复发。GBM的一个决定性特征是其明显的血管增生，这支持肿瘤的进展。这激发了人们对靶向血管生成作为潜在治疗方法的兴趣。Apelin是一种参与血管生成和内皮细胞增殖调节的肽，在GBM的发病机制中起着关键作用。Apelin/APJ信号通路参与促进肿瘤血管化、侵袭性和对治疗的抵抗，使其成为一个有希望的治疗靶点。本文综述了Apelin/APJ通路在GBM进展中的作用，重点讨论了其在血管生成、肿瘤生长和侵袭中的作用。通过整合目前的研究结果，我们旨在建立靶向Apelin信号作为GBM新治疗策略的基本原理，最终目标是克服治疗耐药性并改善患者预后。

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引用次数: 0

Pulmonary veno-occlusive disease: Insights from animal models 肺静脉闭塞性疾病：来自动物模型的见解

IF 3.5 3区医学 Q2 PHARMACOLOGY & PHARMACY

Vascular pharmacology

Pub Date : 2025-09-10 DOI: 10.1016/j.vph.2025.107547

Akiko Hata , Bengisu Gur , Jaspreet Kalra , Amit Prabhakar

Pulmonary veno-occlusive disease (PVOD) is a subtype of pulmonary hypertension (PH) with a poor prognosis. Patients with PVOD develop a gradual increase in pulmonary vascular resistance (PVR) and right heart failure. PVOD can occur sporadically (known as sporadic PVOD or sPVOD) or be inherited (known as heritable PVOD or hPVOD). The estimated incidence rate of PVOD is 0.1–0.5 cases per million, which is about ten times less frequent than that of pulmonary artery hypertension (PAH), a condition closely related to PVOD. Because many clinical features of PVOD overlap with those of PAH, PVOD patients are often misdiagnosed as PAH. There is a critical need for early and accurate diagnosis of PVOD and effective therapeutics for PVOD developed based on its underlying etiology. In this review, we highlight the similarities and distinctions between PAH and PVOD, recent advances in understanding the mechanisms of vascular remodeling in PVOD using animal models, and emerging therapeutic strategies specifically targeting PVOD informed by these insights.

肺静脉闭塞性疾病（PVOD）是肺动脉高压（pH）的一种亚型，预后较差。PVOD患者肺血管阻力（PVR）逐渐增加和右心衰。PVOD可以是偶发的（称为散发性PVOD或sPVOD），也可以是遗传性的（称为遗传性PVOD或hPVOD）。PVOD的估计发病率为0.1-0.5例/百万，比肺动脉高压（PAH）的发病率低约10倍，肺动脉高压是与PVOD密切相关的疾病。由于PVOD的许多临床特征与PAH重叠，PVOD患者常被误诊为PAH。迫切需要对PVOD进行早期准确的诊断，并根据其潜在的病因开发有效的治疗方法。在这篇综述中，我们强调了PAH和PVOD之间的异同，利用动物模型了解PVOD血管重塑机制的最新进展，以及基于这些见解的针对PVOD的新治疗策略。

引用次数: 0

The chemokine receptor CXCR4 and its ligand CXCL12 (SDF-1) localize to ependymal cilia in brain ventricles 趋化因子受体CXCR4及其配体CXCL12 （SDF-1）定位于脑室室管膜纤毛。

IF 3.5 3区医学 Q2 PHARMACOLOGY & PHARMACY

Vascular pharmacology

Pub Date : 2025-09-09 DOI: 10.1016/j.vph.2025.107546

Shahram Eisa-Beygi , Kulandaisamy Arulsamy , Kui Cui , Hao Wu , Beibei Wang , Kaifu Chen , Hong Chen

引用次数: 0

Mesenchymal progenitor cells in perivascular niches: forerunners of mesenchymal stem cells and players in tissue scarring and regeneration 血管周围壁龛中的间充质祖细胞：间充质干细胞的前体和组织瘢痕形成和再生的参与者。

IF 3.5 3区医学 Q2 PHARMACOLOGY & PHARMACY

Vascular pharmacology

Pub Date : 2025-09-04 DOI: 10.1016/j.vph.2025.107533

Neelima Thottapillil , Mirko Corselli , Ian Murray , Reef Hardy , Mario Gomez-Salazar , Joan Casamitjana , Isaac Shaw , Ziyi Wang , Bianca Vezzani , Lijun Ding , Alexander Deneka , Yuyuan Guo , Stefania Giacovazzi , Mihaela Crisan , Aaron James , Bruno Péault

The walls of all embryonic, foetal, and adult blood vessels contain mesodermal progenitors, distributed as pericytes in capillaries and micro vessels, and fibroblastic cells in the tunica adventitia of larger veins and arteries. Following dissociation, selection by flow cytometry, and culture, those perivascular cells turn into bona fide mesenchymal stem cells of which they possess all attributes. In vivo, the adventitial cellular niche supports several spatially-organized subsets of mesodermal progenitors biased toward either osteo-, adipo-, or fibrogenesis, and dominated by more primitive, multi-lineage stem-like cells. Experiments in reporter mice have shown that perivascular progenitor cells play roles in tissue scarring, turnover, and regeneration, but also in pathologic fibrosis and vascular remodelling. This review briefly summarizes the phenotypes, anatomical distribution, and developmental capacities of perivascular mesenchymal progenitor cells, underlining the potential interest thereof for cell therapies, tissue engineering, and disease prediction.

所有胚胎、胎儿和成人血管的壁上都含有中胚层祖细胞，它们以周细胞的形式分布在毛细血管和微血管中，而成纤维细胞则分布在大静脉和动脉的外膜中。经过分离、流式细胞术选择和培养，这些血管周围细胞变成真正的间充质干细胞，它们具有所有的属性。在体内，外基质细胞生态位支持几种空间组织的中胚层祖细胞亚群，这些亚群倾向于成骨、脂肪或纤维形成，并由更原始的多系干细胞样细胞主导。报告小鼠的实验表明，血管周围祖细胞在组织瘢痕、周转和再生中发挥作用，但也在病理性纤维化和血管重塑中发挥作用。本文简要综述了血管周围间充质祖细胞的表型、解剖分布和发育能力，强调了其在细胞治疗、组织工程和疾病预测方面的潜在兴趣。

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引用次数: 0