Vascular endothelial growth factor (VEGF) fails to improve blood flow and to promote collateralization in a diabetic mouse ischemic hindlimb model

Roguin, Ariel; Nitecki, Samy; Rubinstein, Irit; Nevo, Eviatar; Avivi, Aaron; Levy, Nina S.; Abassi, Zaid A.; Sabo, Edmond; Lache, Orit; Frank, Meira; Hoffman, Aaron; Levy, Andrew P.
January 2003
Cardiovascular Diabetology;2003, Vol. 2, p18
Academic Journal
Background: Angiogenic therapy with vascular endothelial growth factor (VEGF) has been proposed as a treatment paradigm for patients suffering from an insufficiency of collateral vessels. Diabetes is associated with increase in the production of VEGF and therefore additional VEGF may not be beneficial. Accordingly, we sought to determine the efficacy of VEGF therapy to augment collateral formation and tissue perfusion in a diabetic mouse ischemic hindlimb model. Methods: Diabetic and non-diabetic mice were studied in parallel for the efficacy of VEGF administration. Diabetes was induced with streptozotocin. Hindlimb ischemia was produced by severing the left iliac artery. An outlet tube from an osmotic infusion pump with placebo/500 micrograms of plasmid-DNA encoding VEGF was fenestrated and tunneled into the left quadriceps muscle. Results: VEGF induced more rapid and complete restoration of blood flow in normal mice. However, in the setting of diabetes there was no difference between VEGF Vs. placebo in the rate or adequacy of flow restoration. There was a significant increase in smooth muscle actin and Factor-VIII antigen densities in diabetic animals and in animals which received VEGF. Conclusions: Angiogenic therapy with VEGF in the setting of diabetes does not appear to have the beneficial effects seen in the absence of diabetes.


Related Articles

  • Evolving Strategies in Manipulating VEGF/VEGFR Signaling for the Promotion of Angiogenesis in Ischemic Muscle. Uchida, C.; Haas, T. L. // Current Pharmaceutical Design;2/1/2009, Vol. 15 Issue 4, p411 

    Peripheral artery disease is characterized by reduced blood flow to the lower limb, resulting in chronic ischemia in these muscles, which can lead to eventual amputation of the affected limb. Stimulation of angiogenesis in the ischemic region would be of therapeutic benefit; however, attempts to...

  • Systemic delivery of miR-126 by miRNA-loaded Bubble liposomes for the treatment of hindlimb ischemia. Yoko Endo-Takahashi; Yoichi Negishi; Arisa Nakamura; Saori Ukai; Kotomi Ooaku; Yusuke Oda; Katsutoshi Sugimoto; Fuminori Moriyasu; Norio Takagi; Ryo Suzuki; Kazuo Maruyama; Yukihiko Aramaki // Scientific Reports;1/24/2014, p1 

    Currently, microRNA(miRNA) is considered an attractive target for therapeutic intervention.Asignificant obstacle to the miRNA-based treatments is the efficient delivery of miRNA to the target tissue. We have developed polyethylene glycol-modified liposomes (Bubble liposomes (BLs)) that entrap...

  • Overview of Ocular Anti-Vascular Endothelial Growth Factor Therapy in the Management of Diabetic Eye Complications. Akiyode, Oluwaranti; Tran, Christine // Diabetes Spectrum;Winter2016, Vol. 29 Issue 1, p44 

    The article discusses the efficacy and safety of anti-vascular endothelial growth factor (VEGF) agents in the management of diabetic eye complications. Topics covered include the results of trials on the use of ranibizumab in people with diabetic macular edema (DME), the comparison of the...

  • PET/SPECT imaging of hindlimb ischemia: focusing on angiogenesis and blood flow. Orbay, Hakan; Hong, Hao; Zhang, Yin; Cai, Weibo // Angiogenesis;Apr2013, Vol. 16 Issue 2, p279 

    Peripheral artery disease (PAD) is a result of the atherosclerotic narrowing of blood vessels to the extremities, and the subsequent tissue ischemia can lead to the up-regulation of angiogenic growth factors and formation of new vessels as a recovery mechanism. Such formation of new vessels can...

  • Expression of Urotensin II During Focal Cerebral Ischemic in Diabetic Rats. Tian, Lin; Li, Yunqian; Hua, Wei; Jia, Ying; Zhou, Min; Gu, Yunhe; Qi, Jiping // Canadian Journal of Neurological Sciences;Jul2014, Vol. 41 Issue 4, p498 

    The article discusses a study aimed at exploring the expression of urotensin II (UII), its receptor, vascular endothelial growth factor (VEGF), and their relations to the ischaemic brains of rats with focal cerebral ischaemia, under normal and diabetic conditions. Methods and results of the...

  • The Optic UK Lecture: bench-to-bedside adventures of a diabetes researcher: results past, results present. Frank, R. N. // Eye;Mar2011, Vol. 25 Issue 3, p331 

    This presentation covers two topics. First is a basic laboratory study, designed to explore the mechanism for the phenomenon of 'early worsening,' in which individuals with type 1 diabetes and early to moderate retinopathy are rapidly placed on 'tight' blood glucose control, after which about...

  • Expression of Angiogenic Factors During Acute Coronary Syndromes in Human Type 2 Diabetes. Marfella, Raffaele; Esposito, Katherine; Nappo, Francesco; Siniscalchi, Mario; Sasso, Ferdinando Carlo; Portoghese, Michele; Di Marino, Maria Pia; Baldi, Alfonso; Cuzzocrea, Salvatore; Di Filippo, Clara; Barboso, Guglielmo; Baldi, Feliciano; Rossi, Francesco; D'Amico, Michele; Giugliano, Dario // Diabetes;Sep2004, Vol. 53 Issue 9, p2383 

    Inadequate angiogenic response to ischemia in diabetic myocardium could result in poor collateral formation. Because hypoxia-inducible factor (HIF)-1α is a transcriptional activator of vascular endothelial growth factor (VEGF) and is critical for initiating angiogenic responses to hypoxia, we...

  • Effect of stimulation frequency on angiogenesis and gene expression in ischemic skeletal muscle of rabbit. Shen, Mei; Gao, Jing; Li, Jianan; Su, Juan // Canadian Journal of Physiology & Pharmacology;May2009, Vol. 87 Issue 5, p396 

    To examine the comparative effects of different frequencies of electrical stimulation (ES) on angiogenesis and gene expression, New Zealand white rabbits with femoral artery ligation in one hindlimb and electrode implantation on the sciatic nerve of the same hindlimb were randomly assigned to 4...

  • Diabetic Microangiopathy: Impact of Impaired Cerebral Vasoreactivity and Delayed Angiogenesis After Permanent Middle Cerebral Artery Occlusion on Stroke Damage and Cerebral Repair in Mice. Poittevin, Marine; Bonnin, Philippe; Pimpie, Cynthia; Rivière, Léa; Sebrié, Catherine; Dohan, Anthony; Pocard, Marc; Charriaut-Marlangue, Christiane; Kubis, Nathalie // Diabetes;Mar2015, Vol. 64 Issue 3, p999 

    Diabetes increases the risk of stroke by three, increases related mortality, and delays recovery. We aimed to characterize functional and structural alterations in cerebral microvasculature before and after experimental cerebral ischemia in a mouse model of type 1 diabetes. We hypothesized that...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics