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Medicine

糖尿病家兔欣德肢体缺血的临床前模型

Published: June 02, 2019
doi:
10.3791/58964
, , , , , ,
1Department of Biomedical Engineering,University of Texas at Austin, 2Division of Cardiology,University of Texas McGovern Medical School, 3Center for Laboratory Animal Medicine and Care,UT Health Science Center at Houston, 4Memorial Herman Heart and Vascular Center,Texas Medical Center, 5Institute for Cellular and Molecular Biology,University of Texas at Austin, 6The Institute for Computational Engineering and Sciences,University of Texas at Austin, 7Institute for Biomaterials, Drug Delivery and Regenerative Medicine,University of Texas at Austin

Summary

我们描述了一种用于诱导高脂血症和糖尿病家兔周围缺血的外科手术。这种手术作为患者外周动脉疾病的临床前模型。血管造影也被描述为一种手段, 以衡量引入缺血和灌注恢复的程度。

Abstract

周围血管疾病是一个普遍的临床问题, 影响到世界各地的数百万病人。周围血管疾病的一个主要后果是缺血的发展。在严重的情况下, 患者可能会出现严重肢体缺血, 在这种情况下, 他们会经历持续的疼痛和截肢的风险增加。目前治疗外周缺血的方法包括旁路手术或经皮介入手术, 如血管成形术与支架置入术或子宫切除术, 以恢复血液流动。然而, 这些治疗方法往往无法持续发展的血管疾病或再狭窄, 或由于患者的整体健康不佳而禁忌症。治疗外周缺血的一种有希望的潜在方法是诱导治疗性的新生血管, 使患者能够发展出附带的血管。这种新形成的网络通过恢复受影响地区的灌注来缓解周围缺血。最常用的外周缺血前模型是利用通过股动脉结扎在健康家兔后肢缺血中的产生。然而, 在过去, 临床前研究的成功与外周缺血治疗的临床试验失败之间存在着严重的脱节。健康的动物通常有强大的血管再生, 以应对手术引起的缺血, 这与慢性周围缺血患者血管和再生的减少形成鲜明对比。在这里, 我们描述了一个优化的动物模型的周围缺血家兔, 包括高脂血症和糖尿病。与胆固醇饮食较高的模型相比, 这种模式减少了附带形成和血压恢复。因此, 该模型可以提供更好的相关性与人类患者的血管生成受损, 从常见的共同疾病伴随周围血管疾病。

Introduction

外周动脉疾病 (PAD) 是一种常见的循环系统疾病, 在这种疾病中, 动脉粥样硬化斑块的形成会导致身体四肢血管变窄。最近动脉粥样硬化危险因素的增加, 包括糖尿病、肥胖和不活动, 导致血管疾病1的发病率不断上升。目前, 据估计, 12%-20% 的60岁以上的普通人群有外周动脉疾病2。外周动脉疾病的一个主要后果是外周缺血的发展, 最常见的是在下肢。在严重的情况下, 患者会出现严重的肢体缺血, 这种状态是由于缺乏血液流动而不断出现疼痛的状态。严重肢体缺血患者在确诊后一年内被截肢的可能性为50%。此外, 糖尿病患者外周动脉疾病的发病率较高, 在干预血运重建 3、4 后, 结果较差。目前治疗外周缺血的方法包括经皮治疗, 如子宫切除术和支架置入或手术旁路。然而, 对许多患者来说, 这些治疗只提供短期好处, 许多治疗对重大外科手术不够健康。在这项工作中, 我们描述了一个临床前动物模型, 用于测试针对周围血管疾病的新治疗方法, 该方法结合了在糖尿病疾病状态下通过手术结扎产生的兔子周围缺血。

对家兔后肢缺血模型已作为阻塞性血管疾病的生理模型, 是半个多世纪以来人类研究的前前兆。由于踝关节和小腿肌肉的肌肉组织发达, 兔子往往是研究外周缺血的首选物种, 而普通的大型动物模型是有蹄类动物 (有蹄的动物)。最近的一些评论讨论了这种模型和其他模型在人类周围血管疾病模型 7,8。在临床前对生长因子9、10、11、12、13、14、 15,16,17,18,19,20, 基因治疗21,22,23, 24,25,26,27,28,29, 30,31, 32, 33,34, 35,36,37,38,39,40,41, 42、43、44和干细胞45、46、47、48、49、50 ,51用于治疗四肢的新生血管。不幸的是, 这些成功的动物研究之后的临床试验并没有显示出对52 人的显著好处。

一个建议的解释, 这种转化失败的原因是, 在人类患者的周围缺血的条件是一个包括抗血管生成信号 53,54,55,56,57,58,59. 几项研究表明, 糖尿病和高血糖的血管生成信号通路存在缺陷。糖尿病和高脂血症导致硫酸肝素蛋白多糖的流失和切割硫酸肝素的酶的增加, 为具有生长因子的治疗血管生成/动脉生成提供了潜在的机制 60,61. 因此, 外周缺血模型的一个关键特征应包括治疗阻力的一个方面, 以便在人类患者疾病状况的背景下评估治疗方法。

在这项工作中, 我们描述了一个兔模型的周围缺血通过手术结扎的股动脉。模型中加入了糖尿病和高脂血症诱导的引线期。我们将这一模型与另一种采用高脂肪饮食的模型进行了比较, 该模型采用了不含糖尿病的高脂肪饮食, 并发现该模型与糖尿病和低脂血症水平较低的关系更有效地减少了血管生长。我们的模型结合了不同群体所使用的进步, 目的是提供实用和标准化的方法, 以在周围血管疾病研究中取得一致的结果。

Protocol

经德克萨斯大学奥斯汀分校和休斯敦机构动物护理和使用委员会 (IACUC) Uthealth科学中心 (IACUC)、美国陆军动物护理和使用审查办公室 (ACURO) 批准, 进行了涉及动物的研究医学研究和材料指挥办公室的研究保护, 并按照国家卫生研究院的动物护理指南。 1. 糖尿病和高脂血症的诱发 新西兰兔子 (4-6个月大) 过渡到一个标准的苜蓿周在4天的过程中0.1% 的胆固醇周。对于第1-5 天, …

Representative Results

在诱导糖尿病和开始0.1% 胆固醇饮食后, 糖尿病和胆固醇饮食家兔的总胆固醇为 123.3±35.1 mg/dL (n = 6只雄性兔子) 的平均总时间点和兔子。这些家兔的 BGL 水平为 248.3±50.4 mg/dL (n = 6只雄性兔子)。图 3显示了典型家兔的血液化学和腿部血压比与胆固醇饮食较高的家兔 (1% 胆固醇) 相比的时间过程。在非糖尿病动物中, 即使胆固醇较高, 我们发现在最后时间点, 缺血性肢…

Discussion

我们提出了一个临床前模型, 以诱导后肢缺血的家兔与糖尿病和高脂血症。在许多研究中, 用于在家兔后肢缺血的技术存在歧义。在小鼠中, 后肢缺血的严重程度和恢复程度与结扎和诱导缺血的技术的位置密切相关。这项工作中提出的技术的意义在于, 它允许糖尿病动物在8周后不能完全恢复的持续诱导缺血。值得注意的是, 当动物被给予较高的胆固醇和脂肪饮食时, 它们能够恢复到接近肢体血压比基…

Disclosures

The authors have nothing to disclose.

Acknowledgements

作者感激地感谢通过国防部国会指导研究计划 (DOD CDMRP) 提供资金;W81XWH-16-1-0582) 至 ABB 和 RS。作者还承认通过美国心脏协会 (17IRG33410888) 提供资金, DOD CDMRP (W81XWH-16-1-0580) 和国家卫生研究院 (1R21EB023551-01; 1RE21EB024147-01A1; 1R01HL141761-01) 至 ABB。

Materials

0.9% Sodium Chloride Henry Schein Medical 1537468 / 1531434 250 mL bag / 1000 mL irrigation btl
1 mL Syringe VWR BD309628
10 mL Syringe VWR BD309695
10% Formalin Fisher-Scientific 23-245684
18G Needle VWR 89219-294
20G Needle VWR 89219-340
25G Needle VWR 89219-290
27G Needle VWR 89219-288
5 mL Syringe VWR BD309646
5% Dextrose Patterson Veterinary 07-800-9689
Acepromazine Patterson Veterinary VEDC207
Alfaxalone Patterson Veterinary 07-891-6051
Alginate Sigma-Aldrich PHR1471-1G
Alloxan Monohydrate Sigma-Aldrich A7413
Angiography Equipment Toshiba Infinix-i
Angiography Injector Medrad
Anti-Mouse Ab Alexa 594 Thermo Fisher Scientific A-11032 Secondary Antibody for IHC
Anti-Rabbit Ab Alexa 488 Thermo Fisher Scientific A-11008 Secondary Antibody for IHC
a-SMA Antibody Abcam ab5694 Primary Antibody for IHC
Baytril Bayer Animal Health 724089904201 Enrofloxacin
Blood Chemistry Panel IDEXX 2616 Rabbit Panel
Blood Pressure Cuff WelchAllyn Flexiport Disposable BP Cuff-infant size 7
Blood Pressure Monitor Vmed Technology Vmed Vet-Dop2
Bupivacaine Henry Schein Medical 6023287
Buprenorphine Patterson Veterinary 42023017905
Buprenorphine SR ZooPharm
Calcium Sulfate CB Minerals Food and Pharmaceutical Grade USP and FCC
Chlorhexidine Scrub Patterson Veterinary 07-888-4598
Chloroform Fisher-Scientific C298-4
Cholesterol Sigma-Aldrich C8503
DAPI Thermo Fisher Scientific 62248
Ear Vein Catheter Patterson Veterinary SR-OX165 Surflo IV catheters
Endotracheal tube Patterson Veterinary Sheridan Brand, Depends on Rabbit Size
Glucometer Amazon B001A67WH2 Accu-Chek Aviva
Glucometer Test Strips McKesson Medical-Surgical 788222 Accu-Chek Aviva Plus
Guidewire Boston Scientific 39122-01
Hair Clippers Amazon B000CQZI3Q Oster #40 blade
Heating Pad Cincinnati Subzero 273
Heating Pad Pump Gaymar Gaymar T/Pump
Hemostat Fine Science Tools 13009-12 Curved Mosquito Hemostat
Heparin Patterson Veterinary
Insertion Tool Merit Medical Systems MAP550 metal wire insertion tool
Insulin HPB Pharmacy Novalin R & Novalin N
Insulin Syringes McKesson Medical-Surgical 942674
Introducer Cook Medical G28954 3F Check Flo Performer Introducer
Isoflurane Henry Schein Medical 1100734
Ketamine Patterson Veterinary 856440301
Lactated Ringers McKesson Medical-Surgical 186662
Lidocaine McKesson Medical-Surgical 239936
Lidocaine/Prilocaine cream McKesson Medical-Surgical 761240
Ligaloop V. Mueller CH117 / CH116 White Mini / Yellow Mini
Mazola Corn Oil Amazon B0049IIVCI
Medrad Syringe McKesson Medical-Surgical 346920 150 mL
Meloxicam Patterson Veterinary
Metal ball sutures Ethicon-Johnson & Johnson K891H 4-0 silk C-1 30"
Metzenbaum Scissors Fine Science Tools 14019-13
Midazolam Henry Schein Medical 1215470
Nitroglycerin McKesson Medical-Surgical 927528
PECAM Antibody Novus Biologicals NB600-562 Primary Antibody for IHC
Perfusion Pump Masterflex
Pigtail Catheter Merit Medical Systems 1310-21-0053 3F pigtail
Polydioxanone (PDS II) suture McKesson Medical-Surgical 129271 4-0 taper RB-1 (needle comes on suture)
Polydioxanone (PDS II) suture McKesson Medical-Surgical 129031 4-0 reverse cutting FS-2
Polyglactin 910 (Vicryl) suture Butler 7233-41 3-0 taper RB-1
Polyglactin 910 (Vicryl) suture McKesson 104373 4-0 reverse cutting FS-2
Rabbit Chow (Alfalfa) LabDiet 5321
Rabbit Restrainer VWR 10718-000
Rib Cutters V. Mueller
Scalpel Fine Science Tools 10003-12
Scalpel Blade Fine Science Tools 10015-00 #15 blade
Silk Sutures Ethicon-Johnson & Johnson A183H 4-0 silk ties 18"
Stainless Steel Ball McMaster-Carr 1598K23 3-mm diameter
Surgical Drapes Gepco 8204S
Syringe Pump DRE Veterinary Versaflow VF-300
Visipaque contrast media McKesson Medical-Surgical 509055
Weitlaner Retractor Fine Science Tools 17012-13
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References

  1. Mozaffarian, D., et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 133 (4), e38-e360 (2016).
  2. Roger, V. L., et al. Heart disease and stroke statistics–2011 update: a report from the American Heart Association. Circulation. 123 (4), e18-e209 (2011).
  3. Shammas, A. N., et al. Limb Outcomes Following Lower Extremity Endovascular Revascularization in Patients With and Without Diabetes Mellitus. Journal of Endovascular Therapy. 24 (3), 376-382 (2017).
  4. Tunstall-Pedoe, H., Peters, S. A. E., Woodward, M., Struthers, A. D., Belch, J. J. F. Twenty-Year Predictors of Peripheral Arterial Disease Compared With Coronary Heart Disease in the Scottish Heart Health Extended Cohort (SHHEC). Journal of the American Heart Association. 6 (9), (2017).
  5. Whiteley, H. J., Stoner, H. B., Threlfall, C. J. The effect of hind limb ischaemia on the physiological activity of rabbit skin). British Journal of Experimental Pathology. 34 (4), 365-375 (1953).
  6. Longland, C. J. Collateral circulation in the limb. Postgraduate Medical Journal. 29 (335), 456-458 (1953).
  7. Waters, R. E., Terjung, R. L., Peters, K. G., Annex, B. H. Preclinical models of human peripheral arterial occlusive disease: implications for investigation of therapeutic agents. Journal of Applied Physiology. 97 (2), 773-780 (2004).
  8. Krishna, S. M., Omer, S. M., Golledge, J. Evaluation of the clinical relevance and limitations of current pre-clinical models of peripheral artery disease. Clinical Science (London. 130 (3), 127-150 (2016).
  9. Zhou, J., et al. Therapeutic angiogenesis using basic fibroblast growth factor in combination with a collagen matrix in chronic hindlimb ischemia). ScientificWorldJournal. , 652794 (2012).
  10. Prochazka, V., et al. Therapeutic Potential of Adipose-Derived Therapeutic Factor Concentrate for Treating Critical Limb Ischemia. Cell Transplantation. 25 (9), 1623-1633 (2016).
  11. Cao, R., et al. Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2. Nature Medicine. 9 (5), 604-613 (2003).
  12. Doi, K., et al. Enhanced angiogenesis by gelatin hydrogels incorporating basic fibroblast growth factor in rabbit model of hind limb ischemia. Heart and Vessels. 22 (2), 104-108 (2007).
  13. Nitta, N., et al. Vascular regeneration by pinpoint delivery of growth factors using a microcatheter reservoir system in a rabbit hind-limb ischemia model. Experimental and Therapeutic. 4 (2), 201-204 (2012).
  14. Karatzas, A., et al. NGF promotes hemodynamic recovery in a rabbit hindlimb ischemic model through trkA- and VEGFR2-dependent pathways. Journal of Cardiovascular Pharmacology. 62 (3), 270-277 (2013).
  15. Stachel, G., et al. SDF-1 fused to a fractalkine stalk and a GPI anchor enables functional neovascularization. Stem Cells. 31 (9), 1795-1805 (2013).
  16. Asahara, T., et al. Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo. Circulation. 92, 365 (1995).
  17. Morishita, R., et al. Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as cytokine supplement therapy. Hypertension. 33 (6), 1379-1384 (1999).
  18. Walder, C. E., et al. Vascular endothelial growth factor augments muscle blood flow and function in a rabbit model of chronic hindlimb ischemia. Journal of Cardiovascular Pharmacology. 27 (1), 91-98 (1996).
  19. Anderson, E. M., et al. VEGF and IGF Delivered from Alginate Hydrogels Promote Stable Perfusion Recovery in Ischemic Hind Limbs of Aged Mice and Young Rabbits. Journal of Vascular Research. 54 (5), 288-298 (2017).
  20. Xie, J., et al. Induction of angiogenesis by controlled delivery of vascular endothelial growth factor using nanoparticles. Cardiovascular Therapeutics. 31 (3), e12-e18 (2013).
  21. Olea, F. D., et al. Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia. Arteriosclerosis, Thrombosis, and Vascular Biology. 35 (1), 184-188 (2015).
  22. Ohara, N., et al. Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promotes collateral development in a rabbit model of hind limb ischemia. Gene Therapy. 8 (11), 837-845 (2001).
  23. Pyun, W. B., et al. Naked DNA expressing two isoforms of hepatocyte growth factor induces collateral artery augmentation in a rabbit model of limb ischemia. Gene Therapy. 17 (12), 1442-1452 (2010).
  24. Kupatt, C., et al. Cotransfection of vascular endothelial growth factor-A and platelet-derived growth factor-B via recombinant adeno-associated virus resolves chronic ischemic malperfusion role of vessel maturation. Journal of the American College of Cardiology. 56 (5), 414-422 (2010).
  25. Olea, F. D., et al. but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia. Gene Therapy. 16 (6), 716-723 (2009).
  26. Pinkenburg, O., et al. Recombinant adeno-associated virus-based gene transfer of cathelicidin induces therapeutic neovascularization preferentially via potent collateral growth. Human Gene Therapy. 20 (2), 159-167 (2009).
  27. Katsu, M., et al. Ex vivo gene delivery of ephrin-B2 induces development of functional collateral vessels in a rabbit model of hind limb ischemia. Journal of Vascular Surgery. 49 (1), 192-198 (2009).
  28. Korpisalo, P., et al. Therapeutic angiogenesis with placental growth factor improves exercise tolerance of ischaemic rabbit hindlimbs. Cardiovascular Research. 80 (2), 263-270 (2008).
  29. Chen, F., Tan, Z., Dong, C. Y., Chen, X., Guo, S. F. Adeno-associated virus vectors simultaneously encoding VEGF and angiopoietin-1 enhances neovascularization in ischemic rabbit hind-limbs. Acta Pharmacologica Sinica. 28 (4), 493-502 (2007).
  30. Kobayashi, K., et al. Combination of in vivo angiopoietin-1 gene transfer and autologous bone marrow cell implantation for functional therapeutic angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology. 26 (7), 1465-1472 (2006).
  31. Lee, J. U., et al. A novel adenoviral gutless vector encoding sphingosine kinase promotes arteriogenesis and improves perfusion in a rabbit hindlimb ischemia model. Coronary Artery Disease. 16 (7), 451-456 (2005).
  32. Nishikage, S., et al. In vivo electroporation enhances plasmid-based gene transfer of basic fibroblast growth factor for the treatment of ischemic limb. Journal of Surgical Research. 120 (1), 37-46 (2004).
  33. Ishii, S., et al. Appropriate control of ex vivo gene therapy delivering basic fibroblast growth factor promotes successful and safe development of collateral vessels in rabbit model of hind limb ischemia. Journal of Vascular Surgery. 39 (3), 629-638 (2004).
  34. Tokunaga, N., et al. Adrenomedullin gene transfer induces therapeutic angiogenesis in a rabbit model of chronic hind limb ischemia: benefits of a novel nonviral vector, gelatin. Circulation. 109 (4), 526-531 (2004).
  35. Yamauchi, A., et al. Pre-administration of angiopoietin-1 followed by VEGF induces functional and mature vascular formation in a rabbit ischemic model. Journal of Gene Medicine. 5 (11), 994-1004 (2003).
  36. Zhong, J., et al. Neovascularization of ischemic tissues by gene delivery of the extracellular matrix protein Del-1. Journal of Clinical Investigation. 112 (1), 30-41 (2003).
  37. Shyu, K. G., Chang, H., Isner, J. M. Synergistic effect of angiopoietin-1 and vascular endothelial growth factor on neoangiogenesis in hypercholesterolemic rabbit model with acute hindlimb ischemia. Life Sciences. 73 (5), 563-579 (2003).
  38. Kasahara, H., et al. Biodegradable gelatin hydrogel potentiates the angiogenic effect of fibroblast growth factor 4 plasmid in rabbit hindlimb ischemia. The Journal of the American College of Cardiology. 41 (6), 1056-1062 (2003).
  39. Rissanen, T. T., et al. Fibroblast growth factor 4 induces vascular permeability, angiogenesis and arteriogenesis in a rabbit hindlimb ischemia model. FASEB Journal. 17 (1), 100-102 (2003).
  40. Taniyama, Y., et al. Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease. Gene Therapy. 8 (3), 181-189 (2001).
  41. Vincent, K. A., et al. Angiogenesis is induced in a rabbit model of hindlimb ischemia by naked DNA encoding an HIF-1alpha/VP16 hybrid transcription factor. Circulation. 102 (18), 2255-2261 (2000).
  42. Gowdak, L. H., et al. Induction of angiogenesis by cationic lipid-mediated VEGF165 gene transfer in the rabbit ischemic hindlimb model. Journal of Vascular Surgery. 32 (2), 343-352 (2000).
  43. Shyu, K. G., Manor, O., Magner, M., Yancopoulos, G. D., Isner, J. M. Direct intramuscular injection of plasmid DNA encoding angiopoietin-1 but not angiopoietin-2 augments revascularization in the rabbit ischemic hindlimb. Circulation. 98 (19), 2081-2087 (1998).
  44. Witzenbichler, B., et al. Vascular endothelial growth factor-C (VEGF-C/VEGF-2) promotes angiogenesis in the setting of tissue ischemia. The American Journal of Pathology. 153 (2), 381-394 (1998).
  45. Prochazka, V., et al. The Role of miR-126 in Critical Limb Ischemia Treatment Using Adipose-Derived Stem Cell Therapeutic Factor Concentrate and Extracellular Matrix Microparticles. Medical Science Monitor. 24, 511-522 (2018).
  46. Wang, J., et al. A cellular delivery system fabricated with autologous BMSCs and collagen scaffold enhances angiogenesis and perfusion in ischemic hind limb. Journal of Biomedical Materials Research Part A. 100 (6), 1438-1447 (2012).
  47. Hao, C., et al. Therapeutic angiogenesis by autologous adipose-derived regenerative cells: comparison with bone marrow mononuclear cells. American Journal of Physiology – Heart and Circulatory Physiology. 307 (6), H869-H879 (2014).
  48. Nemoto, M., et al. Adequate Selection of a Therapeutic Site Enables Efficient Development of Collateral Vessels in Angiogenic Treatment With Bone Marrow Mononuclear Cells. Journal of the American Heart Association. 4 (9), (2015).
  49. Mikami, S., et al. Autologous bone-marrow mesenchymal stem cell implantation and endothelial function in a rabbit ischemic limb model. PLoS One. 8 (7), (2013).
  50. Wang, S., et al. Transplantation of vascular endothelial growth factor 165transfected endothelial progenitor cells for the treatment of limb ischemia. Molecular Medicine Reports. 12 (4), 4967-4974 (2015).
  51. Yin, T., et al. Genetically modified human placentaderived mesenchymal stem cells with FGF2 and PDGFBB enhance neovascularization in a model of hindlimb ischemia. Molecular Medicine Reports. 12 (4), 5093-5099 (2015).
  52. Annex, B. H. Therapeutic angiogenesis for critical limb ischaemia. Nature Reviews Cardiology. 10 (7), 387-396 (2013).
  53. Das, S., et al. Syndesome Therapeutics for Enhancing Diabetic Wound Healing. Advanced Healthcare Materials. 5 (17), 2248-2260 (2016).
  54. Jang, E., Albadawi, H., Watkins, M. T., Edelman, E. R., Baker, A. B. Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle. Proceedings of the National Academy of Sciences of the United States of America. 109 (5), 1679-1684 (2012).
  55. Monteforte, A. J., et al. Glypican-1 nanoliposomes for potentiating growth factor activity in therapeutic angiogenesis. Biomaterials. 94, 45-56 (2016).
  56. Das, S., et al. Syndecan-4 Enhances Therapeutic Angiogenesis after Hind limb Ischemia in Mice with Type 2 Diabetes. Advanced Healthcare Materials. 5 (9), 1008-1013 (2016).
  57. Das, S., Majid, M., Baker, A. B. Syndecan-4 enhances PDGF-BB activity in diabetic wound healing. Acta Biomaterialia. 42, 56-65 (2016).
  58. Das, S., Singh, G., Baker, A. B. Overcoming disease-induced growth factor resistance in therapeutic angiogenesis using recombinant co-receptors delivered by a liposomal system. Biomaterials. 35 (1), 196-205 (2014).
  59. Kikuchi, R., et al. An antiangiogenic isoform of VEGF-A contributes to impaired vascularization in peripheral artery disease. Nature Medicine. 20 (12), 1464-1471 (2014).
  60. Shafat, I., Ilan, N., Zoabi, S., Vlodavsky, I., Nakhoul, F. Heparanase levels are elevated in the urine and plasma of type 2 diabetes patients and associate with blood glucose levels. PLoS One. 6 (2), (2011).
  61. Wang, Y., et al. Endothelial cell heparanase taken up by cardiomyocytes regulates lipoprotein lipase transfer to the coronary lumen after diabetes. Diabetes. 63 (8), 2643-2655 (2014).
  62. Fan, C. L., et al. Therapeutic angiogenesis by intramuscular injection of fibrin particles into ischaemic hindlimbs. Clinical and Experimental Pharmacology and Physiology. 33 (7), 617-622 (2006).
  63. Liddell, R. P., et al. Endovascular model of rabbit hindlimb ischemia: a platform to evaluate therapeutic angiogenesis. Journal of Vascular Interventional Radiology. 16 (7), 991-998 (2005).
  64. Gowdak, L. H., et al. Adenovirus-mediated VEGF(121) gene transfer stimulates angiogenesis in normoperfused skeletal muscle and preserves tissue perfusion after induction of ischemia. Circulation. 102 (121), 565-571 (2000).
  65. Zhang, H., Wang, X., Guan, M., Li, C., Luo, L. Skeletal muscle evaluation by MRI in a rabbit model of acute ischaemia. The British Journal of Radiology. 86 (1026), 20120042 (2013).
  66. Jang, E., Albadawi, H., Watkins, M. T., Edelman, E. R., Baker, A. B. Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle. Proceedings of the National Academy of Sciences of the United States of America. 109 (5), 1679-1684 (2012).
  67. Das, S., et al. Syndesome Therapeutics for Enhancing Diabetic Wound Healing. Advanced Healthcare Materials. 5 (17), 2248-2260 (2016).
  68. Das, S., Majid, M., Baker, A. B. Syndecan-4 enhances PDGF-BB activity in diabetic wound healing. Acta Biomateriala. 42, 56-65 (2016).
  69. Baker, A. B., et al. Regulation of heparanase expression in coronary artery disease in diabetic, hyperlipidemic swine. Atherosclerosis. 213 (2), 436-442 (2010).
  70. Das, S., et al. Syndecan-4 Enhances Therapeutic Angiogenesis after Hind Limb Ischemia in Mice with Type 2 Diabetes. Advanced Healthcare Materials. 5 (9), 1008-1013 (2016).
  71. Popesko, P., Rajtová, V., Ji Horák, . . A Colour Atlas of the Anatomy of Small Laboratory Animals. , (1992).

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Hind Limb IschemiaDiabetic RabbitsPeripheral Arterial DiseaseRegenerative TreatmentNeovascularizationCarotid ArteryHeparinGuidewireAngiographic CatheterContrast AgentNitroglycerinLidocaine
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Sligar, A. D., Howe, G., Goldman, J., Felli, P., Karanam, V., Smalling, R. W., Baker, A. B. Preclinical Model of Hind Limb Ischemia in Diabetic Rabbits. J. Vis. Exp. (148), e58964, doi:10.3791/58964 (2019).
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