Adenovirus‐mediated angiopoietin‐1 gene therapy enhances skin flap survival

Jung, Howard; Gürünlüoğlu, Raffi; Scharpf, Joe; Siemionow, Maria

doi:10.1002/micr.10140

Cited by 25 publications

(15 citation statements)

References 24 publications

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“…Key angiogenic factors include vascular endothelial growth factor (VEGF), transforming growth factor (TGF-␤), fibroblast growth factors (FGF-1 and FGF-2), angiopoietins (Ang-1), tumor necrosis factor (TNF-␣), interleukin 8 (IL-8) and IL-12, and platelet-derived growth factor (PDGF). Many of them have been previously used successfully in stimulating angiogenesis in animal models of experimental flap ischemia [9,10,13,[17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated transforming growth factor-β ameliorates ischemic necrosis of epigastric skin flaps in a rat model1, 2

Huemer¹,

Shafighi²,

Meirer³

et al. 2004

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated transforming growth factor-β ameliorates ischemic necrosis of epigastric skin flaps in a rat model1, 2

Huemer¹,

Shafighi²,

Meirer³

et al. 2004

Journal of Surgical Research

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“…Topical growth factor and cytokine therapy involving single pro-angiogenic proteins as well as adenovirus-mediated VEGF, TGF-b1, and angiopoietin-1 gene therapy have had partial therapeutic neoangiogenic effects in ischemic flaps and grafts [15,16,[33][34][35][36][37]. In an effort to improve the therapeutic index, biomechanical approaches using noninvasive modalities have been utilized to stimulate angiogenesis in ischemic tissue.…”

Section: Discussionmentioning

confidence: 99%

Angiogenic response to extracorporeal shock wave treatment in murine skin isografts

et al. 2008

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Skin grafts are commonly utilized and proven effective methods of open wound coverage. Revascularization through neoangiogenesis is a pivotal mechanism for skin graft integration and durability. Extracorporeal shock-wave treatment (ESWT) has been demonstrated to accelerate wound repair; however, its mechanism-of-action is unclear. We investigated the role of ESWT in early revascularization of full-thickness skin isografts in a murine model. Cohorts of mice were euthanized and skin grafts were harvested 6 h, 2, 4, and 7 days post grafting +/- ESWT. Various aspects of graft neovascularization were measured including gross morphology, quantitative microscopy (vessel number, density), immunohistochemistry (CD31), cDNA SuperArrays for 84 angiogenesis-specific genes, and custom-designed 'Wound Repair' TaqMan Low Density Array (TLDA) cards to assess expression of 188 wound repair genes. We demonstrate that a single administration of ESWT immediately following skin grafting significantly enhances recipient graft revascularization (increased vessel number, size, and density). An augmented early pro-angiogenic and suppressed delayed pro-inflammatory response to ESWT was accompanied by significantly increased expression of both skin graft CD31 and angiogenesis pathway-specific genes, including ELR-CXC chemokines (CXCL1, CXCL2, CXCL5), CC chemokines (CCL2, CCL3, CCL4), cytokines (IL-1 beta, IL-6, G-CSF, VEGF-A), matrix metalloproteinases (MMP3, MMP9, MMP13), hypoxia-inducible factors (HIF-1 alpha), and vascular remodeling kinase (Mst1), as early as 6 h and up to 7 days post grafting and treatment. These findings suggest that early pro-angiogenic and anti-inflammatory effects of ESWT promote tissue revascularization and wound healing by augmenting angiogenesis and dampening inflammation.

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“…Ang1 overexpression in the heart resulted in smaller infarct zones and preserved cardiac function following myocardial infarctions. 29 -31 Improved myoblast survival and reduced tissue necrosis with hindlimb ischemia 96 and enhanced survival of muscle 59,60 and skin 97 flaps have also been reported. These studies showed increases in perfusion and/or capillary density, which were thought to explain the protective effects of Ang1 on the muscle and other tissues.…”

Section: Dallabrida Et Al Angiopoietin-1 Promotes Myocyte Survival E19mentioning

confidence: 98%

Angiopoietin-1 Promotes Cardiac and Skeletal Myocyte Survival Through Integrins

Dallabrida

Ismail²,

Oberle³

et al. 2005

Circulation Research

176

179

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Abstract-Cardiac myocyte loss, regardless of insult, can trigger compensatory myocardial remodeling leading to heart failure. Identifying mediators of cardiac myocyte survival may advance clinical efforts toward myocardial preservation. Angiopoietin-1 limits ischemia-induced cardiac injury. This benefit is ascribed to angiogenesis because the receptor, tie2, is largely endothelial-specific. We propose that direct, non-tie2 interactions of angiopoietin-1 on cardiac myocytes contribute to this cardioprotection. We found that mouse C2C12 skeletal myocytes lack tie2, yet dose-dependently adhered to angiopoietin-1 and angiopoietin-2 similarly to laminin, fibronectin, vitronectin, and more than to collagen-I, -III, and -IV. Adhesion was divalent cation-mediated (Mn 2ϩ , Ca 2ϩ , not Mg 2ϩ ), blocked with EDTA/EGTA, RGD-based peptides, and select integrin subunit antibodies. Similar findings were obtained with human skeletal myocytes (HSMs) and freshly isolated rat neonatal cardiac myocytes (NCMs). Furthermore, angiopoietin-1 conferred significant survival advantage exceeding that of most cell matrices, which was not fully explained by differences in cell adhesion. Angiopoietin-1 promoted survival of serum-starved C2C12, HSM, and NCM (MTT, trypan blue) and prevented taxol-induced apoptosis (caspase-3). Immobilized and soluble angiopoietin-1 phosphorylated Akt S473 and MAPK p42/44 , (not FAK Y397 ) in C2C12 more than in endothelial cells and more than did angiopoietin-2 or cell matrices. EDTA, RGD-based peptides, and some integrin antibodies blocked these responses. Angiopoietin-1 activated HSM and NCM Akt S473 and MAPK p42/44 survival pathways. We propose that this novel function contributes to developmental and cardioprotective actions of angiopoietin-1 presently attributed to vascular effects alone. Angiopoietin-1 may prove therapeutically valuable in cardiac remodeling by supporting myocyte viability and preserving pump function. The full text of this article is available online at http://circres.ahajournals.org. (Circ Res. 2005;96:e8-e24.)Key Words: angiopoietin-1 Ⅲ angiopoietin-2 Ⅲ cardiac myocytes Ⅲ adhesion molecules Ⅲ myocyte apoptosis Ⅲ skeletal myocytes T here is growing consensus that cardiomyocyte (CM) apoptosis contributes to many cardiac diseases (eg, ischemia, 1 infarction, 2 hypertension, 3 myocarditis, 4 transplant rejection, 5 and heart failure 6,7 ). Research efforts are directed at defining the incidence of CM death, the contributions to cardiac dysfunction, and the consequences of inhibiting apoptosis. Incentive is based on the rationale that CM loss reduces contractile mass of the heart and may be a preventable catalyst of heart failure. In support of this concept, low levels of CM apoptosis (23 CM/10 5 nuclei) cause lethal cardiomyopathy in mice. 8 CM apoptosis rates are higher in cardiomyopathy patients (80 to 250 CM/10 5 nuclei) compared with healthy hearts (1 to 10 CM/10 5 nuclei). 9,10 Further, ischemic preconditioning upregulates bcl-2, a cytoprotective protein, and is linked to reduced apop...

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Adenovirus‐mediated angiopoietin‐1 gene therapy enhances skin flap survival

Cited by 25 publications

References 24 publications

Adenovirus-mediated transforming growth factor-β ameliorates ischemic necrosis of epigastric skin flaps in a rat model1, 2

Adenovirus-mediated transforming growth factor-β ameliorates ischemic necrosis of epigastric skin flaps in a rat model1, 2

Angiogenic response to extracorporeal shock wave treatment in murine skin isografts

Angiopoietin-1 Promotes Cardiac and Skeletal Myocyte Survival Through Integrins

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