JVS-vascular science最新文献

Toll-Like Receptor 4, a potential therapeutic target of lower limb ischemic myopathy that raises further questions Toll-Like 受体 4--下肢缺血性肌病的潜在治疗靶点，引发更多疑问

Q3 Medicine

JVS-vascular science

Pub Date : 2024-02-01 DOI: 10.1016/j.jvssci.2024.100195

Ali H. Hakim, Ulf Hedin

引用次数: 0

A central arteriovenous fistula reduces systemic hypertension in a mouse model 中心动静脉瘘可降低小鼠模型的全身性高血压

Q3 Medicine

JVS-vascular science

Pub Date : 2024-02-01 DOI: 10.1016/j.jvssci.2024.100191

Anand H. Brahmandam, Rafael Alves, Hao Liu, Luis Gonzalez, Y. Aoyagi, Yuichi Ohashi, John T. Langford, Carly Thaxton, R. Taniguchi, Weichang Zhang, Hualong Bai, B. Yatsula, Alan Dardik

引用次数: 0

Predicting Future Occlusion or Stenosis of Lower Extremity Bypass Grafts Using Artificial Intelligence to Simultaneously Analyze All Flow Velocities Collected in Current and Previous Ultrasound Exams 利用人工智能同时分析当前和以往超声检查中收集的所有血流速度，预测下肢旁路移植血管未来的闭塞或狭窄情况

Q3 Medicine

JVS-vascular science

Pub Date : 2024-02-01 DOI: 10.1016/j.jvssci.2024.100192

Xiao Luo, Fattah Muhammad Tahabi, Dave M. Rollins, A. Sawchuk

引用次数: 0

Role of Toll-like Receptor 4 in Skeletal Muscle Damage in Chronic Limb Threatening Ischaemia Toll 样受体 4 在慢性肢体缺血损伤中的作用

Q3 Medicine

JVS-vascular science

Pub Date : 2024-02-01 DOI: 10.1016/j.jvssci.2024.100194

Navi Ali, Patel Hemanshu, Shiwen Xu, Baker Daryll, Abraham David, Tsui Janice

引用次数: 0

A porcine model of thoracic aortic aneurysms created with a retrievable drug infusion stent graft mirrors human aneurysm pathophysiology 用可回收药物输注支架制作的猪胸主动脉瘤模型反映了人类动脉瘤的病理生理学特征

Q3 Medicine

JVS-vascular science

Pub Date : 2024-01-01 DOI: 10.1016/j.jvssci.2024.100212

Dahlia M. Kenawy MD , Jordan F. Stafford MD , Foued Amari MS , Drayson Campbell BS , Mahmoud Abdel-Rasoul MS, MPH , Jennifer Leight PhD , Youngjae Chun PhD , Bryan W. Tillman MD, PhD

Objective

Aneurysm pathophysiology remains poorly understood, in part from the disparity of murine models with human physiology and the requirement for invasive aortic exposure to apply agents used to create aneurysm models. A retrievable drug infusion stent graft (RDIS) was developed to isolate the aortic wall intraluminally for drug exposure. We hypothesized that an RDIS could deliver aneurysm-promoting enzymes to create a porcine model of thoracic aneurysms without major surgical exposure.

Methods

Retrievable nitinol stent graft frames were designed with an isolated drug delivery chamber, covered with polytetrafluoroethylene, and connected to a delivery wire with a drug infusion catheter installed to the outer chamber. Institutional Animal Care and Use Committee-approved Yorkshire pigs (n = 5) underwent percutaneous access of the femoral artery, baseline aortogram and stent placement in the thoracic aorta followed by 30-minute exposure to a cocktail of elastase, collagenase, and trypsin. After aspiration of excess drug, stent retrieval, and femoral artery repair, animals were recovered, with angiograms at 1 and 4 weeks followed by explant. Histological analysis, in situ zymography, and multiplex cytokine assays were performed.

Results

The RDIS isolated a segment of anterior aorta angiographically, while the center lumen preserved distal perfusion during drug treatment (baseline femoral mean arterial pressure, 70 ± 14 mm Hg; after RDIS, 75 ± 12; P = .55). Endovascular induction of thoracic aneurysms did not require prior mechanical injury and animals revealed no evidence of toxicity. Within 1 week, significant aneurysmal growth was observed in all five animals (1.4 ± 0.1 cm baseline to 2.9 ± 0.7 cm; P = .002) and only within the treated region of the aorta. Aneurysms persisted out to 4 weeks. Aneurysm histology demonstrated loss of elastin and collagen that was otherwise preserved in untreated aorta. Proinflammatory cytokines and increased matrix metalloproteinase activity were increased significantly within the aneurysm.

Conclusions

An RDIS achieves isolated drug delivery while preserving distal perfusion to achieve an endovascular porcine model of thoracic aneurysms without major surgery. This model may have value for surgical training, device testing, and to better understand aneurysm pathogenesis. Most important, although the RDIS was used to simulate aortic pathology, this tool offers intriguing horizons for focused therapeutic drug delivery directly to aneurysms and, more broadly, focused locoregional drug delivery to vessels and vascular beds.

目的动脉瘤的病理生理学仍然鲜为人知，部分原因是鼠类模型与人体生理学存在差异，而且创建动脉瘤模型时需要对主动脉进行侵入性暴露以使用药物。我们开发了一种可回收药物输注支架移植物（RDIS），用于在腔内隔离主动脉壁以进行药物暴露。我们假设 RDIS 可以在不进行大手术暴露的情况下输送促进动脉瘤形成的酶，从而创建猪胸腔动脉瘤模型。方法设计了可回收镍钛诺支架移植物框架，该框架具有隔离的药物输送室，用聚四氟乙烯覆盖，并与输送导线相连，外室安装有药物输注导管。经动物护理和使用机构委员会批准的约克夏猪（n = 5）接受了经皮股动脉穿刺、基线主动脉造影和胸主动脉支架置入，然后暴露于弹性蛋白酶、胶原酶和胰蛋白酶鸡尾酒中 30 分钟。在抽吸多余药物、取回支架和修复股动脉后，动物得到恢复，并在 1 周和 4 周时进行血管造影，然后进行移植。结果RDIS从血管造影上分离了一段前主动脉，而中心管腔在药物治疗期间保持了远端灌注（基线股动脉平均动脉压为 70 ± 14 mm Hg；RDIS 后为 75 ± 12；P = .55）。胸动脉瘤的血管内诱导无需事先进行机械损伤，动物也未显示出毒性。1 周内，所有 5 只动物的动脉瘤都明显增大（从基线 1.4 ± 0.1 厘米增至 2.9 ± 0.7 厘米；P = .002），且仅在主动脉的治疗区域内。动脉瘤持续存在 4 周。动脉瘤组织学显示弹性蛋白和胶原蛋白流失，而未经治疗的主动脉则保留了这些蛋白和胶原蛋白。结论 RDIS 实现了隔离给药，同时保留了远端灌注，无需大手术即可实现胸动脉瘤的血管内猪模型。该模型可用于外科手术培训、设备测试以及更好地了解动脉瘤的发病机制。最重要的是，虽然 RDIS 是用来模拟主动脉病理的，但这一工具为直接向动脉瘤集中输送治疗药物，以及更广泛地向血管和血管床集中输送局部药物提供了令人感兴趣的前景。

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引用次数: 0

The radiographic relationship of the femoral head, inguinal ligament, and common femoral artery bifurcation for optimal vascular access 股骨头、腹股沟韧带和股总动脉分叉的放射关系，以实现最佳血管通路

Q3 Medicine

JVS-vascular science

Pub Date : 2024-01-01 DOI: 10.1016/j.jvssci.2024.100196

Anand Brahmandam MD , Joshua Huttler BA , Kirthi Bellamkonda MSc , Ocean Setia MD , Jonathan A. Cardella MD , William Stewart PhD , Raul J. Guzman MD , Cassius Iyad Ochoa Chaar MD, MS, MPH

Objective

Common femoral artery (CFA) access is commonly used for endovascular interventions. Access site complications contribute to significant morbidity and mortality. This study characterizes the radiographic variability in the relationship of the femoral head, the inguinal ligament, and the CFA bifurcation, to identify the zone of optimal CFA access.

Methods

Human cadaver dissection of the inguinal ligament and CFA bifurcation was performed. The inguinal ligament and CFA bifurcation were marked with radiopaque pins and plain anteroposterior radiographs were obtained. Radiographic measurements of the femoral head length, the distance of the top of the femoral head to the inguinal ligament, and to the CFA bifurcation were obtained. Results were reported as percentage of femoral head covered by the inguinal ligament or the CFA bifurcation relative to the top of the femoral head. A heatmap was derived to determine a safe access zone between the inguinal ligament and CFA bifurcation.

Results

Forty-five groin dissections (male, n = 20; female, n = 25) were performed in 26 cadavers. The mean overlap of the inguinal ligament with the femoral head was 11.2 mm (range, −19.4 to 27.4 mm). There were no age (<85 vs ≥85 years) or sex-related differences. In 82.6% of cadaveric CFA exposures, there was overlap between the inguinal ligament and femoral head (mean, 27.7%; range, −85.7% to 70.1%), with 55.6% having a >25% overlap. In 11.1%, there was an overlap between the lower one-third of the femoral head and the CFA bifurcation. Cumulatively, heatmap analysis depicted a >80% likelihood of avoiding the inguinal ligament and CFA bifurcation below the midpoint of the femoral head.

Conclusions

Significant variability exists in the relationship between the inguinal ligament, CFA bifurcation, and the femoral head, suggesting the lack of a consistently safe access zone. The safest access zone in >80% of patients lies below the radiographic midpoint of the femoral head and the inferior aspect of the femoral head.

目的股总动脉（CFA）入路通常用于血管内介入治疗。入路部位并发症会导致严重的发病率和死亡率。本研究描述了股骨头、腹股沟韧带和 CFA 分叉关系的影像学变异性，以确定最佳 CFA 入路区域。腹股沟韧带和主动脉分叉处用不透射线的针做标记，并拍摄普通的前胸X光片。对股骨头长度、股骨头顶部到腹股沟韧带的距离以及到CFA分叉的距离进行X光测量。测量结果以腹股沟韧带或CFA分叉相对于股骨头顶部覆盖股骨头的百分比进行报告。结果在26具尸体上进行了45例腹股沟解剖（男性，n = 20；女性，n = 25）。腹股沟韧带与股骨头的平均重叠度为 11.2 毫米（范围：-19.4 至 27.4 毫米）。没有年龄（85 岁与≥85 岁）或性别差异。在82.6%的尸体CFA暴露中，腹股沟韧带和股骨头之间存在重叠（平均为27.7%；范围为-85.7%至70.1%），其中55.6%的重叠率为25%。11.1%的患者股骨头下1/3与CFA分叉处重叠。结论腹股沟韧带、CFA分叉和股骨头之间的关系存在显著差异，表明缺乏一致的安全进入区。80%的患者的最安全入路区位于股骨头放射学中点和股骨头下侧的下方。

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引用次数: 0

Venous thromboembolism swine model with reflux-induced venous hypertension 静脉血栓栓塞症猪模型与反流引起的静脉高血压

Q3 Medicine

JVS-vascular science

Pub Date : 2024-01-01 DOI: 10.1016/j.jvssci.2024.100200

Mengjun Wang MD , Xiao Lu PhD , Ling Han BS , José A. Diaz MD , Seshadri Raju MD , Ghassan S. Kassab PhD

Objective

This study describes a novel swine model of venous thromboembolism (VTE) with reflux-induced venous hypertension.

Methods

Six pigs underwent disruption of the tricuspid chordae tendineae to create reflux and venous hypertension in the femoral vein. The vein was traumatized 2 to 3 weeks later by repeated withdrawal of a slightly overinflated occlusion balloon across the lumen, followed by balloon occlusion of the outflow. A small amount of thrombin was injected into the traumatized vein segment immediately after outflow occlusion. Thrombosis of the traumatized vein evolved into an organized thrombus seven weeks later. The histological features of the harvested post-thrombotic femoral vein were studied with hematoxylin and eosin and Trichrome stains.

Results

In all six pigs, initial disruption of the chordae tendineae was successfully performed to create tricuspid reflux and venous hypertension. After two-stage sequential procedures, a thrombus formed in the target femoral vein segment. Histology of the harvested thrombotic vein showed features of an organizing thrombus with collagen formation and fibrosis.

Conclusions

The novel swine VTE model may serve as a platform for developing and testing human-sized therapeutic procedures and devices in translational venous research.

Clinical Relevance

This study describes a swine model of VTE created by incorporating all three elements of Virchow’s triad. The model uniquely incorporates reflux-induced venous hypertension, which may be used in studying venous insufficiency and VTE in those with systemic venous hypertension. Likewise, this model may serve as a platform for development and evaluation of diagnostic imaging or therapeutic procedures and devices in subjects with systemic venous hypertension.

本研究描述了一种新型猪静脉血栓栓塞症（VTE）模型，该模型具有回流引起的静脉高压。2 到 3 周后，通过反复抽出管腔内略微过度充气的闭塞球囊，对静脉进行创伤，然后用球囊闭塞流出静脉。外流闭塞后，立即向受创静脉段注射少量凝血酶。七周后，受创静脉的血栓形成演变为有组织的血栓。用苏木精、伊红和三色染色法研究了取下的血栓形成后股静脉的组织学特征。经过两个阶段的连续手术后，在目标股静脉段形成了血栓。结论新型猪 VTE 模型可作为开发和测试人体大小的治疗程序和设备的平台，用于静脉转化研究。该模型独特地结合了反流诱导的静脉高压，可用于研究全身性静脉高压患者的静脉功能不全和 VTE。同样，该模型也可作为开发和评估全身性静脉高血压患者诊断成像或治疗程序和设备的平台。

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引用次数: 0

Hyperoxia impairs induced pluripotent stem cell-derived endothelial cells and drives an atherosclerosis-like transcriptional phenotype 高氧损害 iPSC 衍生的内皮细胞并驱动类似动脉粥样硬化的转录表型

Q3 Medicine

JVS-vascular science

Pub Date : 2024-01-01 DOI: 10.1016/j.jvssci.2024.100193

Sean M. Carr PhD , Katherine Owsiany MD, PhD , Ottis Scrivner PhD , Dylan McLaughlin MD , Hanjoong Jo PhD , Luke P. Brewster , Katherine E. Hekman MD, PhD

Background

Induced pluripotent stem cells (iPSCs) directed to endothelial identity (iPSC-ECs) are emerging as a potent tool for regenerative medicine in vascular disease. However, iPSC-ECs lose expression of key identity markers under standard in vitro conditions, limiting their clinical applications.

Methods

To model physiological in vivo conditions, we examined the bioenergetics, presence of key cell markers, and proliferative and angiogenic capacity in iPSC-ECs at late and early passage under hyperoxic (21%) and physiological (4%) oxygen concentrations.

Results

Physoxia resulted in relative preservation of mitochondrial bioenergetic activity, as well as CD144 expression in late passage iPSC-ECs, but not proliferative capacity or tube formation. Single cell RNA sequencing (scRNA-seq) revealed that late passage hyperoxic iPSC-ECs develop an endothelial-to-mesenchymal phenotype. Comparing scRNA-seq data from iPSC-ECs and from atherosclerotic ECs revealed overlap of their transcriptional phenotypes.

Conclusions

Taken together, our studies demonstrate that physiological 4% oxygen culture conditions were sufficient to improve mitochondrial function in high passage cells, but alone was insufficient to preserve angiogenic capacity. Furthermore, late passage cells under typical conditions take on an endothelial-to-mesenchymal phenotype with similarities to ECs found in atherosclerosis.

背景诱导多能干细胞（iPSC）引导内皮身份（iPSC-EC）正在成为血管疾病再生医学的有效工具。方法为了模拟体内生理条件，我们研究了在高氧（21%）和生理氧（4%）浓度下，iPSC-EC 晚期和早期通过时的生物能、关键细胞标志物的存在以及增殖和血管生成能力。结果高氧能相对保留线粒体生物能活性以及晚期iPSC-EC的CD144表达，但不能保留增殖能力或血管形成。单细胞 RNA 测序（scRNA-seq）显示，晚期高氧 iPSC-ECs 形成了内皮细胞到间质细胞的表型。综合来看，我们的研究表明，4% 的生理氧培养条件足以改善高通量细胞的线粒体功能，但仅靠这些条件不足以保持血管生成能力。此外，晚期细胞在典型条件下会出现内皮到间质的表型，与动脉粥样硬化中发现的 EC 相似。

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引用次数: 0

Hypercholesterolemia impairs collateral artery enlargement by ten-eleven translocation 1-dependent hematopoietic stem cell autonomous mechanism in a murine model of limb ischemia 在小鼠肢体缺血模型中，高胆固醇血症通过 Tet1 依赖性造血干细胞自主机制影响侧支动脉扩张

Q3 Medicine

JVS-vascular science

Pub Date : 2024-01-01 DOI: 10.1016/j.jvssci.2024.100203

Jinglian Yan PhD, Guodong Tie PhD, Amanda Tutto MS, Louis M. Messina MD

Objective

The extent of collateral artery enlargement determines the risk of limb loss due to peripheral arterial disease. Hypercholesterolemia impairs collateral artery enlargement, but the underlying mechanism remains poorly characterized. This study tests the hypothesis that hypercholesterolemia impairs collateral artery enlargement through a ten-eleven translocation 1 (Tet1)-dependent hematopoietic stem cell (HSC)-autonomous mechanism that increases their differentiation into proinflammatory Ly6C^hi monocytes and restricts their conversion into proangiogenic Ly6C^low monocytes.

Methods

To test our hypothesis, we induced limb ischemia and generated chimeric mouse models by transplanting HSCs from either wild-type (WT) mice or hypercholesterolemic mice into lethally irradiated WT recipient mice.

Results

We found that the lethally irradiated WT recipient mice reconstituted with HSCs from hypercholesterolemic mice displayed lower blood flow recovery and collateral artery enlargement that was nearly identical to that observed in hypercholesterolemic mice, despite the absence of hypercholesterolemia and consistent with an HSC-autonomous mechanism. We showed that hypercholesterolemia impairs collateral artery enlargement by a Tet1-dependent mechanism that increases HSC differentiation toward proinflammatory Ly6C^hi monocytes and restricts the conversion of Ly6C^hi monocytes into proangiogenic Ly6C^low monocytes. Moreover, Tet1 epigenetically reprograms monocyte gene expression within the HSCs. Restoration of Tet1 expression in HSCs of hypercholesterolemic mice restores WT collateral artery enlargement and blood flow recovery after induction of hindlimb ischemia.

Conclusions

These results show that hypercholesterolemia impairs collateral artery enlargement by a novel Tet1-dependent HSC-autonomous mechanism that epigenetically reprograms monocyte gene expression within the HSCs.

目的：侧支动脉扩张的程度决定了外周动脉疾病导致肢体缺失的风险。高胆固醇血症会影响侧支动脉的扩张，但其潜在机制仍不甚明了。本研究验证了高胆固醇血症通过十-十一转位 1（Tet1）依赖的造血干细胞（HSC）自主机制损害侧支动脉扩张的假设，该机制增加了造血干细胞向促炎性 Ly6Chi 单核细胞的分化，并限制了它们向促血管生成性 Ly6Clow 单核细胞的转化。方法为了验证我们的假设，我们诱导了肢体缺血，并通过将野生型（WT）小鼠或高胆固醇血症小鼠的造血干细胞移植到接受致死性辐照的 WT 受体小鼠体内来生成嵌合小鼠模型。结果我们发现，尽管没有高胆固醇血症，但用高胆固醇血症小鼠的造血干细胞重组的致死辐照 WT 受体小鼠的血流恢复较低，侧支动脉扩大，与高胆固醇血症小鼠观察到的情况几乎相同，这与造血干细胞自主机制一致。我们发现，高胆固醇血症通过一种 Tet1 依赖性机制损害侧支动脉扩张，该机制增加造血干细胞向促炎性 Ly6Chi 单核细胞分化，并限制 Ly6Chi 单核细胞转化为促血管生成的 Ly6Clow 单核细胞。此外，Tet1 还能对造血干细胞内的单核细胞基因表达进行表观遗传重编程。恢复高胆固醇血症小鼠造血干细胞中 Tet1 的表达可恢复 WT 侧支动脉增大和诱导后肢缺血后的血流恢复。

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引用次数: 0

Characterization of a phenol-based model for denervation of the abdominal aorta and its implications for aortic remodeling 基于苯酚的腹主动脉去神经化模型的特征及其对主动脉重塑的影响

Q3 Medicine

JVS-vascular science

Pub Date : 2024-01-01 DOI: 10.1016/j.jvssci.2024.100202

Calvin Chao MD , Caitlyn Dang BS , Nidhi Reddy BA , Sara Alharbi MS , Jimmy Doan , Akashraj Karthikeyan , Brandon Applewhite PhD , Bin Jiang PhD

Objective

Sympathetic innervation plays a pivotal role in regulating cardiovascular health, and its dysregulation is implicated in a wide spectrum of cardiovascular diseases. This study seeks to evaluate the impact of denervation of the abdominal aorta on its morphology and wall homeostasis.

Methods

Male and female Sprague-Dawley rats (N = 12), aged 3 months, underwent midline laparotomy for infrarenal aorta exposure. Chemical denervation was induced via a one-time topical application of 10% phenol (n = 6), whereas sham controls received phosphate-buffered saline (n = 6). Animals were allowed to recover and subsequently were sacrificed after 6 months for analysis encompassing morphology, histology, and immunohistochemistry.

Results

At 6 months post-treatment, abdominal aortas subjected to phenol denervation still exhibited a significant reduction in nerve fiber density compared with sham controls. Denervated aortas demonstrated reduced intima-media thickness, increased elastin fragmentation, decreased expression of vascular smooth muscle proteins (α-SMA and MYH11), and elevated adventitial vascular density. Sex-stratified analyses revealed additional dimorphic responses, particularly in aortic collagen and medial cellular density in female animals.

Conclusions

Single-timepoint phenol-based chemical denervation induces alterations in abdominal aortic morphology and vascular remodeling over a 6-month period. These findings underscore the potential of the sympathetic nervous system as a therapeutic target for aortic pathologies.

Clinical Relevance

Aortic remodeling remains an important consideration in the pathogenesis of aortic disease, including occlusive, aneurysmal, and dissection disease states. The paucity of medical therapies for the treatment of aortic disease has driven considerable interest in elucidating the pathogenesis of these conditions; new therapeutic targets are critically needed. Here, we show significant remodeling after phenol-induced denervation with morphologic, histologic, and immunohistochemical features. Future investigations should integrate sympathetic dysfunction as a potential driver of pathologic aortic wall changes with additional consideration of the sympathetic nervous system as a therapeutic target.

目的交感神经支配在调节心血管健康方面起着关键作用，其失调与多种心血管疾病有关。本研究旨在评估去神经支配腹主动脉对其形态学和壁稳态的影响。方法对 3 个月大的雌雄 Sprague-Dawley 大鼠（12 只）进行中线开腹手术，暴露肾下主动脉。通过一次性局部应用 10% 苯酚诱导化学去神经支配（n = 6），而假对照组则接受磷酸盐缓冲盐水（n = 6）。结果治疗后 6 个月，与假对照组相比，接受苯酚去神经支配的腹主动脉的神经纤维密度仍然显著降低。去神经支配的主动脉显示出内膜厚度减少、弹性蛋白碎片增加、血管平滑肌蛋白（α-SMA 和 MYH11）表达减少以及临近血管密度升高。结论基于苯酚的单时点化学去神经可在 6 个月内诱导腹主动脉形态和血管重塑的改变。临床意义主动脉重塑仍然是主动脉疾病（包括闭塞性、动脉瘤和夹层疾病）发病机制中的一个重要考虑因素。由于缺乏治疗主动脉疾病的药物疗法，人们对阐明这些疾病的发病机制产生了浓厚的兴趣；我们亟需新的治疗靶点。在这里，我们通过形态学、组织学和免疫组织化学特征显示了苯酚诱导去神经化后的明显重塑。未来的研究应将交感神经功能障碍作为主动脉壁病理变化的潜在驱动因素，并进一步考虑将交感神经系统作为治疗靶点。

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引用次数: 0