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Hind limb ischemia

Yun Wang, Qing-Jiang Pang, Jiang-Tao Liu, Hai-Hao Wu, Dong-Ying Tao
MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII). The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1...
March 15, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Hiroshi Chadani, Soichiro Usui, Oto Inoue, Takashi Kusayama, Shin-Ichiro Takashima, Takeshi Kato, Hisayoshi Murai, Hiroshi Furusho, Ayano Nomura, Hirofumi Misu, Toshinari Takamura, Shuichi Kaneko, Masayuki Takamura
Selenoprotein P (SeP), a liver-derived secretory protein, functions as a selenium supply protein in the body. SeP has been reported to be associated with insulin resistance in humans through serial analysis of gene expression. Recently, SeP has been found to inhibit vascular endothelial growth factor-stimulated cell proliferation in human umbilical vein endothelial cells, and impair angiogenesis in a mouse hind limb model. In this study, the role of SeP in ischemia/reperfusion (I/R) injury has been investigated...
March 16, 2018: International Journal of Molecular Sciences
Tatyana Merkulova-Rainon, Chris S Mantsounga, Dong Broquères-You, Cristina Pinto, José Vilar, Diana Cifuentes, Philippe Bonnin, Nathalie Kubis, Daniel Henrion, Jean-Sébastien Silvestre, Bernard I Lévy
The pathophysiology of sporadic Alzheimer's disease (AD) remains uncertain. Along with brain amyloid-β (Aβ) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0...
March 7, 2018: Angiogenesis
Jun Yu, Alan Dardik
Therapeutic angiogenesis offers promise as a novel treatment that is complementary to surgical or endovascular procedures for peripheral arterial diseases (PAD). Appropriate development and use of hind limb ischemia models is necessary for successful studies of therapeutic angiogenesis and/or arteriogenesis. In this chapter, we describe two commonly used murine unilateral hind limb ischemia models, the femoral artery transection model and the femoral/saphenous artery excision model.
2018: Methods in Molecular Biology
Yanbo Fan, Haocheng Lu, Wenying Liang, Minerva T Garcia-Barrio, Yanhong Guo, Ji Zhang, Tianqing Zhu, Yibai Hao, Jifeng Zhang, Y E Chen
<u>Rationale:</u> Post-ischemic angiogenesis is critical to limit the ischemic tissue damage and improve the blood flow recovery. The regulation and the underlying molecular mechanisms of post-ischemic angiogenesis are not fully unraveled. Transcription factor-EB (TFEB) is emerging as a master gene for autophagy and lysosome biogenesis. However, the role of TFEB in vascular disease is less understood. <u>Objective:</u> We aimed to determine the role of endothelial TFEB in post-ischemic angiogenesis and its underlying molecular mechanism...
February 21, 2018: Circulation Research
Ruixiang Li, Jianming Liang, Yuwei He, Jing Qin, Huining He, Seungjin Lee, Zhiqing Pang, Jianxin Wang
The outcome of scaffold-based stem cell transplantation remains unsatisfied due to the poor survival of transplanted cells. One of the major hurdles associated with the stem cell survival is the immune rejection, which can be effectively reduced by the use of immunosuppressant. However, ideal localized and sustained release of immunosuppressant is difficult to be realized, because it is arduous to hold the drug delivery system within scaffold for a long period of time. In the present study, the sustained release of immunosuppressant for the purpose of improving the survival of stem cells was successfully realized by a nanoparticle-anchoring hydrogel scaffold we developed...
2018: Theranostics
Rajesh Gupta, Alexander R Mackie, Sol Misener, Lijun Liu, Douglas W Losordo, Raj Kishore
Sonic Hedgehog (Shh) signaling induces neovascularization and angiogenesis. It is not known whether the hedgehog signaling pathway in endothelial cells is essential to angiogenesis. Smoothened (Smo) transduces hedgehog signaling across the cell membrane. This study assessed whether endothelial Smoothened-dependent Shh signaling is required for Shh-mediated angiogenesis and ischemic tissue repair. Endothelial-specific smoothened knockout mice, eSmo Null were created using Cre-lox recombination system. eSmo Null mice had no observable phenotype at baseline and showed normal cardiac function...
February 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Senthilkumar Alagesan, Clara Sanz-Nogués, Xizhe Chen, Michael Creane, Thomas Ritter, Rhodri Ceredig, Timothy O'Brien, Matthew D Griffin
Allogeneic mesenchymal stromal cells (allo-MSC) are a promising "off-the-shelf" therapy with anti-inflammatory and pro-repair properties. This study investigated humoral immune responses to intramuscular (IM) injections of allo-MSC. Total and isotype-specific anti-donor IgG and donor-specific complement-mediated lysis were determined in sera from healthy mice two weeks after single or repeated IM injections of fully-MHC-mismatched allo-MSC with comparison to mice receiving syngeneic MSC, allogeneic splenocytes or saline...
February 15, 2018: Immunology and Cell Biology
Zhifang Zheng, Yishu Liu, Lulu Zhu, Jianbing Tang, Wenhua Huang, Biao Cheng
BACKGROUND: The effect of lumbar sympathectomy for the treatment of lower limb ischemia remains a matter of controversy. METHODS: Sprague-Dawley rats were subjected to lumbar sympathectomy, after which Evans blue dye was injected into the hind plantar skin. Extravasation of dye was measured and compared with rats undergoing sham operation. Hind plantar skin was processed for HE staining, immunohistochemistry, and Western blot. RESULTS: In sympathectomized rats, blue stained areas in hind plantar skin and concentrations of Evans blue were significantly less than that of sham sympathectomy (control) rats, both 2 weeks and 3 months after surgery...
2018: Clinical Hemorheology and Microcirculation
Abbygail A Foster, Ruby E Dewi, Lei Cai, Luqia Hou, Zachary Strassberg, Cynthia A Alcazar, Sarah C Heilshorn, Ngan F Huang
A key feature of peripheral arterial disease (PAD) is damage to endothelial cells (ECs), resulting in lower limb pain and restricted blood flow. Recent preclinical studies demonstrate that the transplantation of ECs via direct injection into the affected limb can result in significantly improved blood circulation. Unfortunately, the clinical application of this therapy has been limited by low cell viability and poor cell function. To address these limitations we have developed an injectable, recombinant hydrogel, termed SHIELD (Shear-thinning Hydrogel for Injectable Encapsulation and Long-term Delivery) for cell transplantation...
February 6, 2018: Biomaterials Science
Shengye Zhang, Jane Shaw-Boden, Yara Banz, Anjan K Bongoni, Adriano Taddeo, Rolf Spirig, Marc W Nolte, Peter J Cowan, Robert Rieben
OBJECTIVE: Ischemia-reperfusion (I/R) injury is a major clinical problem linked to vascular surgery. Currently, no drugs to prevent or to treat I/R injury are approved for clinical use. C1 inhibitor (C1 INH) is known to reduce activation of the plasma cascade systems that are involved in the pathophysiologic process of I/R injury. The aim of this study was therefore to investigate the effect of C1 INH on complement deposition and endothelial cell activation in a rat model of hind limb I/R injury...
January 27, 2018: Journal of Vascular Surgery
Tyler T Cooper, Stephen E Sherman, Miljan Kuljanin, Gillian I Bell, Gilles A Lajoie, David A Hess
Blood-derived progenitor cell transplantation holds potential for the treatment of severe vascular diseases. Human umbilical cord blood (UCB)-derived hematopoietic progenitor cells purified using high aldehyde dehydrogenase (ALDH hi ) activity demonstrate pro-angiogenic functions following intramuscular (i.m.) transplantation into immunodeficient mice with hind-limb ischemia. Unfortunately, UCB ALDH hi cells are rare and prolonged ex vivo expansion leads to loss of high ALDH-activity and diminished vascular regenerative function...
January 27, 2018: Stem Cells
Václav Procházka, Jana Jurčíková, Kateřina Vítková, Lubomír Pavliska, Ludmila Porubová, Ondrej Lassák, Piotr Buszman, Carlos A Fernandez, František Jalůvka, Iveta Špačková, Ivo Lochman, Martin Procházka, Mária Janíková, Zdeněk Tauber, Jana Franková, Martin Lachnit, Michael C Hiles, Brian H Johnstone
BACKGROUND Paracrine factors secreted by adipose-derived stem cells can be captured, fractionated, and concentrated to produce therapeutic factor concentrate (TFC). The present study examined whether TFC effects could be enhanced by combining TFC with a biological matrix to provide sustained release of factors in the target region. MATERIAL AND METHODS Unilateral hind limb ischemia was induced in rabbits. Ischemic limbs were injected with either placebo control, TFC, micronized small intestinal submucosa tissue (SIS), or TFC absorbed to SIS...
January 26, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Caroline Caradu, Alexandre Guy, Chloé James, Annabel Reynaud, Alain-Pierre Gadeau, Marie-Ange Renault
Aim: The purpose of the present study was to investigate the role of endogenous Shh in ischemia-induced angiogenesis. Methods and results: To this aim, we used inducible Shh knock-out (KO) mice and unexpectedly found that capillary density was significantly increased in regenerating muscle of Shh deficient mice 5 days after hind limb ischemia (HLI) was induced, demonstrating that endogenous Shh does not promote angiogenesis but more likely limits it. Myosin and MyoD expression were equivalent in Shh deficient mice and control mice, indicating that endogenous Shh is not required for ischemia-induced myogenesis...
January 22, 2018: Cardiovascular Research
Megumi Fuke, Makoto Narita, Yuko Wada, Tatsuichiro Seto, Kenji Okada, Jun Nakayama, Hiroto Izumi, Ken-Ichi Ito
Critical limb ischemia (CLI) is the most severe complication of peripheral arterial disease (PAD). Understanding the molecular mechanisms underlying tissue repair after CLI is necessary for preventing PAD progression. Y-box binding protein-1 (YB-1) regulates the expression of many genes in response to environmental stresses. We aimed to determine whether YB-1 is involved in ischemic muscle regeneration. A mouse ischemic hind-limb model was generated; namely, the femoral, saphenous, and popliteal arteries in the left hind limb were ligated...
2018: Tohoku Journal of Experimental Medicine
Huixian Li, Xiuhua Dong, Mu Jin, Weiping Cheng
BACKGROUND: Delayed paraplegia due to spinal cord ischemia/reperfusion injury (IRI) remains one of the most severe complications of thoracoabdominal aneurysm surgery, for which effective prevention and treatment is still lacking. OBJECTIVES: The current study investigates whether spinal cord stimulation (SCS) postconditioning has neuroprotective effects against spinal cord IRI. METHOD: Ninety-six New Zealand white male rabbits were randomly divided into four groups as follows: a sham group and three experimental groups (C group, 2 Hz group, and 50 Hz group) n = 24/group...
January 18, 2018: Neuromodulation: Journal of the International Neuromodulation Society
Andreas Engel Krag, Christine Lodberg Hvas, Birgitte Jul Kiil, Gete Toft Eschen, Tine Engberg Damsgaard, Anne-Mette Hvas
BACKGROUND: Remote ischemic conditioning (RIC) administered by non-lethal periods of extremity ischemia and reperfusion attenuates ischemia-reperfusion injury. We aimed to investigate the local and systemic coagulation marker response to flap ischemia-reperfusion injury, and the effects of RIC on coagulation markers following flap ischemia-reperfusion injury. METHODS: A musculocutaneous latissimus dorsi flap was subjected to 4 h of ischemia followed by 7 h of reperfusion in 16 female Danish Landrace pigs (39 kg)...
January 8, 2018: Microsurgery
Pei-Ling Hsieh, Viktoriya Rybalko, Aaron B Baker, Laura J Suggs, Roger P Farrar
OBJECTIVE: Peripheral arterial disease can cause not only ischemia but also skeletal muscle damage. It has been known that macrophages (MPs) play an important role in coordinating muscle repair; however, phenotype transition of monocyte-MP in ischemic muscle has not been well defined. Hence, the purpose of this study was to examine the temporal recruitment of MPs and to explore their therapeutic effect on ischemic muscle regeneration. METHODS: Unilateral femoral artery excision was performed on C57BL/6 mice...
December 19, 2017: Journal of Vascular Surgery
Xiaona Zhou, Runzhu Jiang, Yucai Dong, Lifeng Wang
The use of cardiopulmonary bypass (CPB) in cardiac surgeries is known to induce pathological changes in vital organs such as lungs. Remote ischemic preconditioning (RIPC) is a protective strategy that has shown to be able to reduce tissue damage related to ischemia-reperfusion injury (IRI). The current study seeks to evaluate the beneficial effects of limb RIPC on lung tissues and function in a rat CPB model. RIPC, which consisted of three cycles of 5-min ischemia and subsequently 5-min reperfusion, was induced in the hind limbs of the animals via a tourniquet...
2017: PloS One
Agnes Dwi Ariyanti, Julita Sisjayawan, Jing Zhang, Jian-Qi Zhang, Gui-Xue Wang, Makoto Miyagishi, Shou-Rong Wu, Vivi Kasim
Hind-limb ischemia (HLI) is one of the major complication of diabetic patients. Angiogenesis potential in diabetic patients is severely disrupted, and the mechanism underlying it has not been fully elucidated, making it an obstacle for developing an efficient therapeutic angiogenesis strategy. Skeletal muscle cells, through their paracrine function, had been known to be critical for neoangiogenesis. Here we found that hyperglycemia upregulates the expression of skeletal muscle cells prolyl hydroxylase domain 3 (PHD3), which resulted in the decrease of the secretion of angiogenic factors, especially VEGF-A and PDGF-BB...
November 14, 2017: Oncotarget
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