Estimation of systemic distribution and angiogenic effect of pl-VEGF165 in the model of limb ischemia
Published 2016-01-14
Keywords
- gene therapy,
- chronical limb ischemia,
- vascular endothelial growth factor,
- VEGF,
- plasmid
- pharmacokinetics ...More
How to Cite
Copyright (c) 2016 Yudin M.A., Plaksa I.L., Mzhavanadze N.D., Krakovskii M.A., Bykov V.N., Mavlikeev M.O., Isaev A.A., Kalinin R.E., Deev R.V.

This work is licensed under a Creative Commons Attribution 4.0 International License.
Abstract
The group of cardio-vascular diseases accompanied by ischemia is the leading cause of a death in the world. Regarding this issue, creating the novel pharmacy drugs reducing ischemia and integrating them in a routine clinical practice is pivotal. The therapeutic angiogenesis with gene therapy drugs is considered like a prospective approach at this field. The gene constructions included a gene one of the angiogenic growth factors can be used as an instrument for blood flow restoration in ischemic tissues by increasing an amount of microvascular vessels. However, there are some traditional safety precautions and concerns connected with its potential systemic effect which can cause vessels growth on the distance and lead to complications. In this paper pharmacokinetic qualities of gene construction on a base of plasmid with a gene of vascular endothelial growth factor are described. The efficiency of an angiogenic effect was estimated on animal model with chronic ischemia of lower limb.
References
- Павлинский С.Л., Шабалкин П.И., Исаев А.А., Деев Р.В. Оценка стоимости-эффективности геннотерапевтического препарата «Неоваскулген» в лечении хронической ишемии нижних конечностей // Вестник Северо-Западного государственного медицинского университета им. И.И. Мечникова. 2014. № 2. С. 54–59.
- Кунгурцев В.В., Дибиров М.Д., Шиманко А.И. Реконструктивные операции при критической ишемии у лиц пожилого и старческого возраста с бедренно-подколенно-берцовой окклюзией // Ангиология и сосудистая хирургия. 1998. № 2. С. 180.
- Wiley Gene Therapy Clinical Trials Worldwide [интернет]. Режим доступа: http://www.wiley.com/legacy/wileychi/genmed/clinical/
- Gupta R., Tongers J., Losordo D.W. Human studies of angiogenic gene therapy // Circ. Res. 2009. Vol. 9. P. 724–36.
- Douglas L., Tongers J., Losordo D.W. Human Studies of Angiogenic Gene Therapy // Circ. Res. 2009. Vol. 105. № 8. P. 724–736.
- Houk B.E., Hochhaus G., Hughes J.A. Kinetic modeling of plasmid DNA degradation in rat plasma // AAPS PharmSci. 1999. Vol. 1. № 3. Р. 9.
- Wolff J.A., Dowty M.E., Jiao S., Repetto G., Berg R.K., Ludtke J.J., Williams P., Slautterback D.B. Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscle // J. Cell Sci. 1992. Vol. 103. № 4. Р. 1249–1308.
- Tokunaga N., Nagaya N., Shirai M., Tanaka E., Ishibashi-Ueda H., Harada-Shiba M., Kanda M., Ito T., Shimizu W., Tabata Y., Uematsu M., Nishigami K., Sano S., Kangawa K., Mori H. Adrenomedullin gene transfer induces therapeutic angiogenesis in a rabbit model of chronic hind limb ischemia // Circulation Res. 2004. Vol. 109. P. 526–531.
- Li W., Tanaka K., Ihaya A., Fujibayashi Y., Takamatsu S., Morioka K., Sasaki M., Uesaka T., Kimura T., Yamada N., Tsuda T., Chiba Y. Gene therapy for chronic myocardial ischemia using platelet-derived endothelial cell growth factor in dogs // Am. J. Physiol.Heart Circ. Physiol. 2005. Vol. 288. P. 408–415.
- Laguens R., Cabeza Meckert P., Vera Janavel G., Del Valle H., Lascano E., Negroni J., Werba P., Cuniberti L., Martínez V., Melo C., Papouchado M., Ojeda R., Criscuolo M., Crottogini A. Entrance in mitosis of adult cardiomyocytes in ischemic pig hearts after plasmid-mediated rhVEGF165 gene transfer // Gene Therapy. 2002. Vol. 9. P. 1676–1681.
- Yoon Y.S., Uchida S., Masuo O., Cejna M., Park J.S., Gwon H.C., Kirchmair R., Bahlman F., Walter D., Curry C., Hanley A., Isner J.M., Losordo D.W. Progressive attenuation of myocardial vascular endothelial growth factor expression is and recovery of cardiac function in diabetic cardiomyopathy after replenishment of a seminal event in Diabetic Cardiomyopathy: Restoration of Microvascular Homeostasis Local Vascular Endothelial Growth Factor // Circulation. 2005. Vol. 111. P. 2073-2085.