Vascular Endothelial Growth Factor Gene Therapy in Improvement of Skin Paddle Survival in a Rat TRAM Flap Model

Zhang, Feng; Yang, Feixue; Hu, Eric C.; Sones, William; Lei, Man-Ping; Lineaweaver, William C.

doi:10.1055/s-2005-915207

Cited by 19 publications

(23 citation statements)

References 38 publications

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“…Specifically, local subdermal or subcutaneous injection of liposomal or adenoviral vectors encoding the cDNA of VEGF-165 at 0.5, 2, 3, 7, or 14 days before surgery effectively augmented skin flap viability in the rat, but the mechanism was not studied (9,11,20,21). Local subcutaneous injection of VEGF-165 plasmid DNA 7 days preoperatively also increased skin viability in rat musculocutaneous flaps, and again the mechanism was not studied (49). Other investigators observed that local adenovirus-mediated VEGF-165 gene therapy induced angiogenesis in the skin of the mouse ear and in rat skin flaps (32,46), but the mechanism was also not studied.…”

mentioning

confidence: 99%

Efficacy and mechanism of adenovirus-mediated VEGF-165 gene therapy for augmentation of skin flap viability

Huang¹,

Khan²,

Ashrafpour³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Skin ischemic necrosis due to vasospasm and/or insufficient vascularity is the most common complication in the distal portion of the skin flap in reconstructive surgery. This project was designed to test our hypothesis that preoperative subdermal injection of adenoviral vectors encoding genes for vascular endothelial growth factor-165 (Ad.VEGF-165) or endothelial nitric oxide (NO) synthase (Ad.eNOS) effectively augments skin viability in skin flap surgery and that the mechanism of Ad.VEGF-165 gene therapy involves an increase in synthesis/release of the angiogenic and vasodilator factor NO. PBS (0.5 ml) or PBS containing Ad.VEGF-165, Ad.eNOS, or adenovirus (Ad.Null) was injected subdermally into the distal half of a mapped rat dorsal skin flap (4 × 10 cm) 7 days preoperatively, and skin flap viability was assessed 7 days postoperatively. Local subdermal gene therapy with 2 × 107–2 × 1010 plaque-forming units of VEGF-165 increased skin flap viability compared with PBS- or Ad.Null-injected control ( P < 0.05). Subdermal Ad.VEGF-165 and Ad.eNOS gene therapies were equally effective in increasing skin flap viability at 5 × 108 plaque-forming units. Subdermal Ad.VEGF-165 therapy was associated with upregulation of eNOS protein expression, Ca2+-dependent NOS activity, synthesis/release of NO, and increase in capillary density and blood flow in the distal portion of the skin flap. Injection of the NOS inhibitor Nω-nitro-l-arginine (15 mg/kg im), but not the cyclooxygenase inhibitor indomethacin (5 mg/kg im), 45 min preoperatively completely abolished the increase in skin flap blood flow and viability induced by Ad.VEGF-165 injected subdermally into the mapped skin flap 7 days preoperatively. We have demonstrated for the first time that 1) Ad.VEGF-165 and Ad.eNOS mapped skin flap injected subdermally into the mapped skin flap 7 days preoperatively are equally effective in augmenting viability in the rat dorsal skin flap compared with control, 2) the mechanism of subdermal Ad.VEGF-165 gene therapy in augmenting skin flap viability involves an increase in NO synthesis/release downstream of upregulation of eNOS protein expression and Ca2+-dependent NOS activity, and 3) the vasodilating effect of NO may predominantly mediate subdermal Ad.VEGF gene therapy in augmenting skin flap blood flow and viability.

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mentioning

confidence: 99%

Efficacy and mechanism of adenovirus-mediated VEGF-165 gene therapy for augmentation of skin flap viability

Huang¹,

Khan²,

Ashrafpour³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…VEGF gene therapy has been used to improve flap viability with promising results in experimental settings. [27,28] In the present study, VEGF gene therapy was administered by intramuscular injection to the muscle flap in order to create a VEGF-enriched microenvironment in osteomyelitis-induced bone. In histological examination, less inflammation and more fibrosis was found in the VEGF gene-transfected muscle flap group (Group 4), compared to the group that received muscle flap without VEGF gene-transfection (Group 3).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Transpositional Muscle Flaps Transfected with Vascular Endothelial Growth Factor Gene in the Treatment of Experimental Osteomyelitis

Aliyev¹,

Aykan

Eski

et al. 2015

Ulus Travma Acil Cerrahi Derg

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“…These measurements coincided with the clinical improvement of the patient's pain-free walking distance. The effects of shock waves on distal ischemic skin flap necrosis were examined in rats using different skin flap models [13,[19][20][21]. All studies showed a significant increase in mean percentage of the flap survival area after ESWA and can be seen as an indicator of improved local perfusion.…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

“…In another study of cardiac ESWA, enhanced coronary angiogenesis was associated with reduced angina pectoris in patients with severe coronary artery disease, whereby no adverse effects were noted [18]. Accordingly, improved local perfusion was suggested after ESWA-associated reduction of necrosis using an epigastric skin flap model and a dorsal skin random flap model, respectively [13,[19][20][21]. The exposition of human umbilical vascular endothelial cells (HUVECs) to low dose ESWA revealed a significant upregulation of VEGF m-RNA protein, indicating a direct vascular effect [22].…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

Microvascular Response to Shock Wave Application in Striated Skin Muscle

Calcagni

Chen

Högger

et al. 2011

Journal of Surgical Research

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Background: This study aims to quantify by intravital microscopy the microhemodynamic response after extracorporeal shock wave application (ESWA) to the physiologic microcirculation of the mouse dorsal skinfold chamber.Materials and Methods: ESWA was carried out using an electrohydraulic shock wave source. Two different shock wave doses of 500 and 1000 pulses at an energy flux rate of 0.08 mJ/mm2 and a frequency of 4 Hz were compared with sham-operated animals. Microcirculatory analyses were performed at baseline (BL) and during a 3 d observation period after ESWA. The expression of caspase-3 (casp-3), proliferating cell nuclear antibody (PCNA), von Willebrand factor (vWF), and endothelial nitric oxide synthase (eNOS) were analyzed semiquantitatively by immunohistochemistry.Results: ESWA provoked a significant and persistent increase of functional capillary density (FCD) throughout the observation period, reaching a maximum (140% ± 5% of BL, P < 0.05 versus sham) after 1 d when animals were treated with 1000 pulses. ESWA induced a slight increase of leukocyte rolling (not, vert, similar2-to not, vert, similar3.5-fold, P < 0.05) and leukocyte adherence (not, vert, similar1.5-to not, vert, similar2-fold, P < 0.05) to the endothelial lining of postcapillary venules. One day following ESWA, we observed enhanced expression of casp-3 (not, vert, similar3-to not, vert, similar4-fold), PCNA (not, vert, similar9-to not, vert, similar14-fold), vWF (not, vert, similar11-to not, vert, similar14-fold), and eNOS (not, vert, similar3-fold), all P < 0.05.Conclusion: This study shows that ESWA provokes a favorable persistent increase of patent capillaries, however accompanied by a transient and slight inflammatory response but also by dose-dependant apoptotic cell death. Our data suggest that ESWA might represent a noninvasive biomechanical tool to treat critically perfused and endangered tissues, but certainly warrants further investigation. Background. This study aims to quantify by intravital microscopy the microhemodynamic response after extracorporeal shock wave application (ESWA) to the physiologic microcirculation of the mouse dorsal skinfold chamber. U N C O R R E C T E D P R O O FMaterials and Methods. ESWA was carried out using an electrohydraulic shock wave source. Two different shock wave doses of 500 and 1000 pulses at an energy flux rate of 0.08 mJ/mm 2 and a frequency of 4 Hz were compared with sham-operated animals. Microcirculatory analyses were performed at baseline (BL) and during a 3 d observation period after ESWA. The expression of caspase-3 (casp-3), proliferating cell nuclear antibody (PCNA), von Willebrand factor (vWF), and endothelial nitric oxide synthase (eNOS) were analyzed semiquantitatively by immunohistochemistry.Results. ESWA provoked a significant and persistent increase of functional capillary density (FCD) throughout the observation period, reaching a maximum (140% ± 5% of BL, P < 0.05 versus sham) after 1 d when animals were treated with 1000 pulses. ESWA induced a slight increase of ...

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Vascular Endothelial Growth Factor Gene Therapy in Improvement of Skin Paddle Survival in a Rat TRAM Flap Model

Cited by 19 publications

References 38 publications

Efficacy and mechanism of adenovirus-mediated VEGF-165 gene therapy for augmentation of skin flap viability

Efficacy and mechanism of adenovirus-mediated VEGF-165 gene therapy for augmentation of skin flap viability

The Effects of Transpositional Muscle Flaps Transfected with Vascular Endothelial Growth Factor Gene in the Treatment of Experimental Osteomyelitis

Microvascular Response to Shock Wave Application in Striated Skin Muscle

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