Astragalosides promote angiogenesis via vascular endothelial growth factor and basic fibroblast growth factor in a rat model of myocardial infarction

Yu,Jun-Min; Zhang,Xiao-Bo; Jiang,Wen; Wang,Hui-Dong; Zhang,Yi-Na

doi:10.3892/mmr.2015.4307

Astragalosides promote angiogenesis via vascular endothelial growth factor and basic fibroblast growth factor in a rat model of myocardial infarction

Authors:
- Jun-Min Yu
- Xiao-Bo Zhang
- Wen Jiang
- Hui-Dong Wang
- Yi-Na Zhang
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Affiliations: Department of Gerontology, The Fourth Clinical Medical College, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Gerontology, The Second Clinical Medical College, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: September 9, 2015 https://doi.org/10.3892/mmr.2015.4307
Pages: 6718-6726
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to evaluate the effect of astragalosides (ASTs) on angiogenesis, as well as the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) following myocardial infarction (MI). MI was induced in rats by ligation of the left coronary artery. Twenty‑four hours after surgery, the rats were divided into low‑dose, high‑dose, control and sham surgery groups (n=8 per group). The low‑ and high‑dose groups were treated with ASTs (2.5 and 10 mg/kg/day, respectively, via intraperitoneal injection), while, the control and sham surgery group rats received saline. Serum levels, and mRNA and protein expression levels of VEGF and bFGF, as well as the microvessel density (MVD) were determined four weeks post‑treatment. Twenty‑four hours post‑surgery, VEGF and bFGF serum levels were observed to be comparable between the groups; while at four weeks, the VEGF and bFGF levels were higher in the AST‑treated rats (P<0.01). Similarly, VEGF and bFGF mRNA and protein expression levels were higher following AST treatment (P<0.05). No difference in VEGF mRNA expression between the low‑ and high‑dose groups was noted, however, an increase in the bFGF expression levels was detected in the high‑dose group. Newly generated blood vessels were observed following MI, with a significant increase in MVD observed in the AST‑treated groups (P<0.05). AST promotes angiogenesis of the heart and increases VEGF and bFGF expression levels. Thus, it is hypothesized that increased VEGF and bFGF levels may contribute to the AST‑induced increase in angiogenesis in rat models of MI.

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1	Orphanou K, Stassopoulou A and Keravnou E: Risk assessment for primary coronary heart disease event using dynamic Bayesian networks. Artificial Intelligence in Medicine. Holmes J, Bellazzi R, Sacchi L and Peek N: 9105. Springer International Publishing; pp. 161–165. 2015, View Article : Google Scholar
2	Liu Y and Liu RX: The research progress of Traditional Chinese medicine in treatment of coronary atherosclerosis heart disease. Hebei J of Trad Chin Med. 35:1476–1478. 2013.In Chinese.
3	Tao HM, Qin S and Zhang DY: Research progress of coronary heart disease in women. Adv Cardiovasc Dis. 35:250–253. 2014.In Chinese.
4	Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, et al: Executive summary: Heart disease and stroke statistics-2013 update: A report from the American heart association. Circulation. 127:143–152. 2013. View Article : Google Scholar : PubMed/NCBI
5	Li XY and Fu ZQ: Pharmacotherapy of coronary heart disease in the elderly. J Med Res. 40:3–5. 2011.In Chinese.
6	de bakker JM, van capelle FJ, Janse MJ, Wilde AA, Coronel R, Becker AE, Dingemans KP, van Hemel NM and Hauer RN: Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: Electrophysiologic and anatomic correlation. Circulation. 77:589–606. 1988. View Article : Google Scholar : PubMed/NCBI
7	Wang LM, Zhang SD and Ann YC: Treatment of ventricular arrhythmia after myocardial infarction. Chinese Journal of Cardiovascular Review. 6:144–146. 2008.In Chinese.
8	Meng QC: Treatment and prevention of reperfusion arrhythmia after thrombolytic therapy for acute myocardial infarction. Journal of Medical Forum. 27:55–57. 2006.In Chinese.
9	Bates ER and Topol EJ: Limitations of thrombolytic therapy for acute myocardial infarction complicated by congestive heart failure and cardiogenic shock. J Am Coll Cardiol. 18:1077–1084. 1991. View Article : Google Scholar : PubMed/NCBI
10	Kones R: Primary prevention of coronary heart disease: Integration of new data, evolving views, revised goals and role of rosuvastatin in management. A comprehensive survey. Drug Des Devel Ther. 5:325–380. 2011. View Article : Google Scholar
11	Ware JA and Simons M: Angiogenesis in ischemicheart disease. Nat Med. 3:158–164. 1997. View Article : Google Scholar : PubMed/NCBI
12	Rissanen TT, Korpisalo P, Markkanen JE, Liimatainen T, Ordén MR, Kholová I, de Goede A, Heikura T, Gröhn OH and Ylä-Herttuala S: Blood flow remodels growing vasculature during vascular endothelial growth factor gene therapy and determines between capillary arterialization and sprouting angiogenesis. Circulation. 112:3937–3946. 2005. View Article : Google Scholar : PubMed/NCBI
13	Dragneva G, Korpisalo P and Ylä-Herttuala S: Promoting blood vessel growth in ischemic diseases: Challenges in translating preclinical potential into clinical success. Dis Model Mech. 6:312–322. 2013. View Article : Google Scholar : PubMed/NCBI
14	Liu Q, Li J, Wang J, Li J, Janicki JS and Fan D: Effects and mechanisms of Chinese herbal medicine in ameliorating myocardial ischemia-reperfusion injury. Evid Based Complement Alternat Med. 2013:9256252013.PubMed/NCBI
15	Liu YF, Liu SW and Liu ZX: Effects of Ginsenosiee Rb1 on blood vessel regeneration after ischemia and reperfusion in rats. Chin J Histochem Cytochem. 17:39–44. 2008.In Chinese.
16	Han D, Zhang Y, Liu M, et al: The hemodynamic and antioxidant effects of Astragaloside on ventricular remodeling rats. Chin J Lab Diag. 17:1956–1959. 2013.In Chinese.
17	Wang YP, Li XY, Song CQ and Hu ZB: Effect of astragaloside IV on T, B lymphocyte proliferation and peritoneal macrophage function in mice. Acta Pharmacol Sin. 23:263–266. 2002.PubMed/NCBI
18	Yin Y, Li WP, Gong HL, Zhu FF, Li WZ and Wu GC: Protective effect of astragaloside on focal cerebral ischemia/reperfusion injury in rats. Am J Chin Med. 38:517–527. 2010. View Article : Google Scholar : PubMed/NCBI
19	Yang JS, Yu JM, Ju L, et al: Effects of Astragalosides on angiogenesis in myocardium infarction rats. Chin J Prim Med Pharm. 19:215–217. 2012.
20	Zhang L, Liu Q, Lu L, Zhao X, Gao X and Wang Y: Astragaloside IV stimulates angiogenesis and increases hypoxia-inducible factor-1α accumulation via phosphatidylinositol 3-kinase/Akt pathway. J Pharmacol Exp Ther. 338:485–491. 2011. View Article : Google Scholar : PubMed/NCBI
21	De Luca A, Carotenuto A, Rachiglio A, Gallo M, Maiello MR, Aldinucci D, Pinto A and Normanno N: The role of the EGFR signaling in tumor microenvironment. J Cell Physiol. 214:559–567. 2008. View Article : Google Scholar
22	Böttcher RT and Niehrs C: Fibroblast growth factor signaling during early vertebrate development. Endocr Rev. 26:63–77. 2005. View Article : Google Scholar : PubMed/NCBI
23	Andersson H and Brittebo E: Proangiogenic effects of environmentally relevant levels of bisphenol A in human primary endothelial cells. Arch Toxicol. 86:465–474. 2012. View Article : Google Scholar
24	Clark JD, Gebhart GF, Gonder JC, Keeling ME and Kohn DF: Special Report: The 1996 Guide for the Care and Use of Laboratory Animals. ILAR J. 38:41–48. 1997. View Article : Google Scholar : PubMed/NCBI
25	Reddy BY, Greco SJ, Patel PS, Trzaska KA and Rameshwar P: RE-1-silencing transcription factor shows tumor-suppressor functions and negatively regulates the oncogenic TAC1 in breast cancer cells. Proc Natl Acad Sci U S A. 106:4408–4413. 2009. View Article : Google Scholar : PubMed/NCBI
26	Weidner N: Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol. 147:9–19. 1995.PubMed/NCBI
27	Aurgemma GP and Gaasch WH: Quantitative evaluation of left ventricular structure, wall stress, and systolic function. The Practice of Clinical Echocardiography. Otto CM: 2nd edition. Elsevier Saunders; Philadelphia, PA: pp. 65–87. 2002
28	Meiners S, Dreger H, Fechner M, Bieler S, Rother W, Günther C, Baumann G, Stangl V and Stangl K: Suppression of cardio-myocyte hypertrophy by inhibition of the ubiquitin-proteasome system. Hypertension. 51:302–308. 2008. View Article : Google Scholar
29	Cochain C, Channon KM and Silvestre JS: Angiogenesis in the infarcted myocardium. Antioxid Redox Signal. 18:1100–1113. 2013. View Article : Google Scholar :
30	Hicklin DJ and Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 23:1011–1027. 2005. View Article : Google Scholar
31	Pohl-Schickinger A, Koehne P, Schmitz T, Schmitt KR, Hübler M, Redlin M, Berger F and Stiller B: Vascular endothelial growth factor and its soluble receptor in infants with congenital cardiac disease. Cardiol Young. 20:505–508. 2010. View Article : Google Scholar : PubMed/NCBI
32	Shibuya M: VEGF-VEGFR signals in health and disease. Biomol Ther. 22:1–9. 2014. View Article : Google Scholar
33	Wafai R, Tudor EM, Angus JA and Wright CE: Vascular effects of FGF-2and VEGF-B in rabbits with bilateral hind limb ischemia. J Vasc Res. 46:45–54. 2009. View Article : Google Scholar
34	Schirmer SH, van Nooijen FC, Piek JJ and van Royen N: Stimulation of collateral artery growth: Travelling further down the road to clinical application. Heart. 95:191–197. 2009. View Article : Google Scholar : PubMed/NCBI
35	Zhang Y, Hu G, Li S, Li ZH, Lam CO, Hong SJ, Kwan YW, Chan SW, Leung GP and Lee SM: Pro-angiogenic activity of astragaloside IV in HUVECs in vitro and zebrafish in vivo. Mol Med Rep. 5:805–811. 2012.
36	Karanu FN, Murdoch B, Gallacher L, Wu DM, Koremoto M, Sakano S and Bhatia M: The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells. J Exp Med. 192:1365–1372. 2000. View Article : Google Scholar : PubMed/NCBI
37	Benedito R, Roca C, Sörensen I, Adams S, Gossler A, Fruttiger M and Adams RH: The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. Cell. 137:1124–1135. 2009. View Article : Google Scholar : PubMed/NCBI
38	Hernandez SL, Banerjee D, Garcia A, Kangsamaksin T, Cheng WY, Anastassiou D, Funahashi Y, Kadenhe-Chiweshe A, Shawber CJ, Kitajewski JK, et al: Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis. Vasc Cell. 5:172013. View Article : Google Scholar : PubMed/NCBI