Tag Archives: VEGF
miR-329-containing exosomes derived from breast tumor cells suppress VEGF and KDM1A expression in endothelial cells
N. Maleki1,2,3*, F. Karami1, S. Heyati2, M. HadiZadeh3, Gh. Parnian4*
1Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Islamic Azad University-Tehran North Branch, Tehran, Iran;
*e-mail: dr.nargesmaleki@yahoo.com;
2Gynecology and reproductive biology Department, Kowsar poly-clinic, Tehran, Iran;
3Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
4Appletree Medical group, 275 Dundad W (Grange), Toronto, Ontario, Canada;
*e-mail: ghazalehparnian1@gmail.com
Received: 03 February 2021; Accepted: 07 July 2021
The exosomal transfer of miRNAs from tumor cells is considered to modulate VEGF expression and angiogenesis in endothelial cells. The aim of our investigation was to focus exclusively on the ability of specific exosomal miR329 to regulate angiogenesis within breast tumor. All experiments were done on MCF-7 and HUVEC cell lines. Exosomes were derived from MCF-7 cells both untreated and treated with tamoxifen that is an effecrive suppressor of hormone receptor-positive breast cancer. The level of miR32 and its targeted genes VEGF and lysine (K)-specific demethylase 1A (KDM1A) expression was estimated with q-RT-PCR. The PKH26 red fluorescent labeling kit was used to label the isolated exosomes and monitor their uptake. It was shown that the relative amount of miR-329 in exosomes was twice as large as in breast cancer cells. Fluorescence microscopy imaging presented that exosomes from MCF-7 cells were able to penetrate into endothelial cells and concentrate in the cytoplasm. It was observed that exosomes derived from untreated breast cancer cells induced KDM1A and VEGF gene expressions whereas exosomes from tamoxifen-treated cancer cells induced time-dependent decrease of KDM1A and VEGF expression in endothelial cells. It is assumed that the transfer of miR-329 containing exosomes from tamoxifen treated breast cancer cells to the endothelial cells could repress angiogenic molecular signaling pathway and be used as a supplementary strategy in breast cancer treatment.
Vitamin D(3) regulates hepatic VEGF-A and apelin expression in experimental type 1 diabetes
D. O. Labudzynskyi1*, I. O. Shymanskyi1, O. O. Lisakovska1,
A. O. Mazanova1, L. V. Natrus2, M. M. Veliky1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Bogomolets National Medical University, Kyiv, Ukraine;
*e-mail: konsument3@gmail.com
Received: 09 July 2019; Accepted: 15 May 2020
The deficiency of vitamin D is associated with the risk of various chronic diseases, including diabetes mellitus and its complications. Given the strong genomic action of vitamin D hormone-active form, its deficiency can lead to dysfunction of cytokine signaling pathways, including those dependent on vascular endothelial growth factors (VEGFs) and apelin. The present study was carried out to define the link between VEGF-A and apelin expression in liver, hepatocytes viability and vitamin D status at experimental type 1 diabetes in mice. We established that chronic hyperglycemia at streptozotocin-induced diabetes was accompanied by a 2.2-fold decrease in 25OHD content in the serum and increased hepatocytes apoptosis and necrosis. Vitamin D deficiency correlated with increased apelin and VEGF-A (8- and 1.6-fold respectively) expression. Almost complete restoration of circulatory 25OHD content in serum was achieved at vitamin D3 treatment (800 IU/kg, per os, for 2 months) followed by reduced apelin and VEGF-A expression in liver and the decline of hepatocytes apoptosis. We conclude that vitamin D3 can be involved in cell survival, angiogenesis and fibrogenesis by modulating VEGF-A and apelin dependent regulatory systems in diabetic liver.
Levels of angiogenic regulators and MMP-2, -9 activities in Martorell ulcer: a case report
O. M. Petrenko1, A. A. Tykhomyrov2
1Bogomolets National Medical University, Kyiv, Ukraine;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine;
e-mail: artem_tykhomyrov@ukr.net
Received: 27 July 2018; Accepted: 13 December 2018
Martorell hypertensive ischemic leg ulcers (HYTILU) represent a unique form of lower extremity non-healing ulcers that develop in association with poorly controlled high blood pressure. The present study was performed in order to assess levels of protein regulators of angiogenesis (vascular endothelial growth factor, or VEGF, and angiostatins) and to evaluate activities of matrix metalloproteinases (MMPs) (gelatinases MMP-2 and -9) in wound cutaneous tissue in the case of patient with 2-years HYTILU history. VEGF and angiostatin levels were analyzed by Western blot, MMP activities were evaluated by gelatin zymography. We report here for the first time that wound tissue in HYTILU is characterized with increased levels of VEGF (by 75 folds vs. histologically normal tissue, P < 0.01) and dramatic overproduction of angiostatin levels, which are undetectable in healthy cutaneous tissue. Approximately 10-fold elevation in MMP-2 and -9 activities is observed in wound tissue as compared with uninjured cutaneous tissue. Obtained results indicate that increased production of angiogenic inhibitors, angiostatins, may counteract VEGF-induced pro-angiogenic signaling, and together with MMP overactivation, contributes to failed healing of ischemic ulcer. Further extended studies are needed to clarify how changes of angiogenic profile and imbalance of proteolytic activities in non-healing Martorell ulcers can be considered during their management procedures to improve efficacy of surgery debridement and/or skin grafting.
Effects of Pistacia atlantica resin oil on the level of VEGF, hydroxyproline, antioxidant and wound healing activity in STZ-induced diabetic rats
B. Shahouzehi1, M. Shabani2, N. Shahrokhi3, S. Sadeghiyan4, Y. Masoumi-Ardakani5*
1Cardiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
e-mail: bshahouzehi@yahoo.com;
2Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran;
3Department of Physiology, Afzalipour School of Medicine & Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran;
4Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran;
5Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
e-mail: ymab125@gmail.com
Diabetes mellitus is a chronic metabolic disorder which is followed by many complications. One of these problems following diabetes is diabetic ulcers and 2.5% of diabetic patients develop foot ulcer annually. Natural resources are useful stock for finding traditional treatment. Studies which examined Pistacia atlantica properties showed that it has some beneficial effects including: antimicrobial, antifungal, antioxidant and wound healing. Yet, Pistacia atlantica resin oil effects on diabetic wound have not been examined. Therefore, we evaluate Pistacia atlantica resin oil antioxidant and wound healing activity. Sprague-Dawley male rats were entered to the study and randomly grouped (n = 10) as follows: group 1 – control group – burnt rats which received neither STZ nor Pistacia atlantica resin oil; group 2 – diabetic burnt rats; group 3 – diabetic burnt rats which received 250 µl/day Pistacia atlantica resin oil topically as an ointment for two weeks. At the end of the study antioxidant status, Vascular Endothelial Growth Factor (VEGF) and hydroxyproline contents were examined in the wound area. Our results showed that Pistacia atlantica resin oil has remarkable antioxidant activity in STZ-induced diabetic rats. Also, it promoted VEGF and hydroxyproline contents in the wound area which showed that it increases angiogenesis and collagen turnover in the diabetic wound. We concluded that Pistacia atlantica resin oil can be considered as a new therapeutic agent in diabetic wound healing, and also it is safe, available and cheap treatment of other wounds and skin injuries.
The mechanism of VEGF-mediated endothelial cells survival and proliferation in conditions of unfed-culture
T. V. Nikolaienko, V. V. Nikulina, D. V. Shelest, L. V. Garmanchuk
Educational and Scientific Centre “Institute of Biology”,
Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: nikolaenkotetiana@yandex.ua
The mechanisms of VEGF-mediated effects on endothelial cells during cancer development and progression is not clear. In present study the biological effects of VEGF, VEGF-rich culture medium of peritoneal macrophages from mice with Lewis lung carcinoma were studied on MAEC cell line under conditions of unfed culture. We have shown that VEGF increased cell proliferation by the 5th day of culturing vs control and anti-VEGF-treated cells. This effect was associated with increased consumption of glucose and NO production by the 2nd day while decreased – on the 5th day of cell culturing. VEGF-mediated NO production was dependent on Ca2+ ions. Block of Ca2+-channels (LaCl3) had more pronounced inhibitory effect vs chelator of Ca2+ ions (EDTA). It was shown that peritoneal macrophages are the main suppliers of VEGF at tumor angiogenesis, as evidenced by the data obtained on model system of endothelial cells synchronized in G0/G1 phase.