Profilin‑1 contributes to cardiac injury induced by advanced glycation end‑products in rats

Yang,Dafeng; Liu,Weiwei; Ma,Liping; Wang,Ya; Ma,Jing; Jiang,Minna; Deng,Xu; Huang,Fang; Yang,Tianlun; Chen,Meifang

doi:10.3892/mmr.2017.7446

Profilin‑1 contributes to cardiac injury induced by advanced glycation end‑products in rats

Authors:
- Dafeng Yang
- Weiwei Liu
- Liping Ma
- Ya Wang
- Jing Ma
- Minna Jiang
- Xu Deng
- Fang Huang
- Tianlun Yang
- Meifang Chen
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Affiliations: Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Cardiology, The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China, Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China, Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410006, P.R. China, Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: September 8, 2017 https://doi.org/10.3892/mmr.2017.7446
Pages: 6634-6641
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cardiac injury, including hypertrophy and fibrosis, induced by advanced glycation end products (AGEs) has an important function in the onset and development of diabetic cardiomyopathy. Profilin‑1, a ubiquitously expressed and multifunctional actin‑binding protein, has been reported to be an important mediator in cardiac hypertrophy and fibrosis. However, whether profilin‑1 is involved in AGE‑induced cardiac hypertrophy and fibrosis remains to be determined. Therefore, the present study aimed to investigate the function of profilin‑1 in cardiac injury induced by AGEs. The model of cardiac injury was established by chronic tail vein injection of AGEs (50 mg/kg/day for 8 weeks) in Sprague‑Dawley rats. Rats were randomly assigned to control, AGEs, AGEs + profilin‑1 shRNA adenovirus vectors (AGEs + S)or AGEs + control adenovirus vectors (AGEs + V) groups. Profilin‑1 shRNA adenovirus vectors were injected via the tail vein to knockdown profilin‑1 expression at a dose of 3x109 plaque forming units every 4 weeks. Echocardiography was performed to measure cardiac contractile function. Cardiac tissues were stained with Masson's trichrome stain to evaluate ventricular remodeling. The serum levels of procollagen type III N‑terminal peptide were detected by ELISA. The expression of profilin‑1, receptor for AGEs (RAGE), Rho, p65, atrial natriuretic peptide, β‑myosin heavy chain, matrix metalloproteinase (MMP)‑2 and MMP‑9 were determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and/or western blot analysis and immunohistochemistry staining. The results demonstrated that chronic injection of exogenous AGEs led to cardiac dysfunction, hypertrophy and fibrosis, as determined by echocardiography, Masson trichrome staining and the expression of associated genes. The expression of profilin‑1 was markedly increased in heart tissue at the mRNA and protein level following AGE administration, as determined by RT‑qPCR and western blotting, which was further confirmed by immunohistochemistry staining. Furthermore, the expression of RAGE, Rho and p65 was also increased at the protein level. Notably, knockdown of profilin‑1 expression ameliorated AGE‑induced cardiac injury and reduced the expression of RAGE, Rho and p65. These results indicate an important role for profilin‑1 in AGE‑induced cardiac injury, which may provide a novel therapeutic target for patients with diabetic heart failure.

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1	Miki T, Yuda S, Kouzu H and Miura T: Diabetic cardiomyopathy: Pathophysiology and clinical features. Heart Fail Rev. 18:149–166. 2013. View Article : Google Scholar : PubMed/NCBI
2	Bodiga VL, Eda SR and Bodiga S: Advanced glycation end products: Role in pathology of diabetic cardiomyopathy. Heart Fail Rev. 19:49–63. 2014. View Article : Google Scholar : PubMed/NCBI
3	Sveen KA, Nerdrum T, Hanssen KF, Brekke M, Torjesen PA, Strauch CM, Sell DR, Monnier VM, Dahl-Jørgensen K and Steine K: Impaired left ventricular function and myocardial blood flow reserve in patients with long-term type 1 diabetes and no significant coronary artery disease: Associations with protein glycation. Diab Vasc Dis Res. 11:84–91. 2014. View Article : Google Scholar : PubMed/NCBI
4	Cooper ME: Importance of advanced glycation end products in diabetes-associated cardiovascular and renal disease. Am J Hypertens. 17:31S–38S. 2004. View Article : Google Scholar : PubMed/NCBI
5	Ko SY, Lin IH, Shieh TM, Ko HA, Chen HI, Chi TC, Chang SS and Hsu YC: Cell hypertrophy and MEK/ERK phosphorylation are regulated by glyceraldehyde-derived AGEs in cardiomyocyte H9c2 cells. Cell Biochem Biophys. 66:537–544. 2013. View Article : Google Scholar : PubMed/NCBI
6	Li SY, Sigmon VK, Babcock SA and Ren J: Advanced glycation endproduct induces ROS accumulation, apoptosis, MAP kinase activation and nuclear O-GlcNAcylation in human cardiac myocytes. Life Sci. 80:1051–1056. 2007. View Article : Google Scholar : PubMed/NCBI
7	Guo R, Liu W, Liu B, Zhang B, Li W and Xu Y: SIRT1 suppresses cardiomyocyte apoptosis in diabetic cardiomyopathy: An insight into endoplasmic reticulum stress response mechanism. Int J Cardiol. 191:36–45. 2015. View Article : Google Scholar : PubMed/NCBI
8	Brouwers O, de Vos-Houben JM, Niessen PM, Miyata T, van Nieuwenhoven F, Janssen BJ, Hageman G, Stehouwer CD and Schalkwijk CG: Mild oxidative damage in the diabetic rat heart is attenuated by glyoxalase-1 overexpression. Int J Mol Sci. 14:15724–15739. 2013. View Article : Google Scholar : PubMed/NCBI
9	Pernier J, Shekhar S, Jegou A, Guichard B and Carlier MF: Profilin interaction with actin filament barbed end controls dynamic instability, capping, branching, and motility. Dev Cell. 36:201–214. 2016. View Article : Google Scholar : PubMed/NCBI
10	Witke W: The role of profilin complexes in cell motility and other cellular processes. Trends Cell Biol. 14:461–469. 2004. View Article : Google Scholar : PubMed/NCBI
11	Jockusch BM, Murk K and Rothkegel M: The profile of profilins. Rev Physiol Biochem Pharmacol. 159:131–149. 2007.PubMed/NCBI
12	Li Z, Zhong Q, Yang T, Xie X and Chen M: The role of profilin-1 in endothelial cell injury induced by advanced glycation end products (AGEs). Cardiovasc Diabetol. 12:1412013. View Article : Google Scholar : PubMed/NCBI
13	Romeo G, Frangioni JV and Kazlauskas A: Profilin acts downstream of LDL to mediate diabetic endothelial cell dysfunction. FASEB J. 18:725–727. 2004.PubMed/NCBI
14	Cheng JF, Ni GH, Chen MF, Li YJ, Wang YJ, Wang CL, Yuan Q, Shi RZ, Hu CP and Yang TL: Involvement of profilin-1 in angiotensin II-induced vascular smooth muscle cell proliferation. Vascul Pharmacol. 55:34–41. 2011. View Article : Google Scholar : PubMed/NCBI
15	Jin HY, Song B, Oudit GY, Davidge ST, Yu HM, Jiang YY, Gao PJ, Zhu DL, Ning G, Kassiri Z, et al: ACE2 deficiency enhances angiotensin II-mediated aortic profilin-1 expression, inflammation and peroxynitrite production. PLoS One. 7:e385022012. View Article : Google Scholar : PubMed/NCBI
16	Caglayan E, Romeo GR, Kappert K, Odenthal M, Südkamp M, Body SC, Shernan SK, Hackbusch D, Vantler M, Kazlauskas A and Rosenkranz S: Profilin-1 is expressed in human atherosclerotic plaques and induces atherogenic effects on vascular smooth muscle cells. PLoS One. 5:e136082010. View Article : Google Scholar : PubMed/NCBI
17	Kooij V, Viswanathan MC, Lee DI, Rainer PP, Schmidt W, Kronert WA, Harding SE, Kass DA, Bernstein SI, Van Eyk JE and Cammarato A: Profilin modulates sarcomeric organization and mediates cardiomyocyte hypertrophy. Cardiovasc Res. 110:238–248. 2016. View Article : Google Scholar : PubMed/NCBI
18	Zhao SH, Qiu J, Wang Y, Ji X, Liu XJ, You BA, Sheng YP, Li X and Gao HQ: Profilin-1 promotes the development of hypertension-induced cardiac hypertrophy. J Hypertens. 31:576–586. 2013. View Article : Google Scholar : PubMed/NCBI
19	Elnakish MT, Hassanain HH and Janssen PM: Vascular remodeling-associated hypertension leads to left ventricular hypertrophy and contractile dysfunction in profilin-1 transgenic mice. J Cardiovasc Pharmacol. 60:544–552. 2012. View Article : Google Scholar : PubMed/NCBI
20	Hein S, Kostin S, Heling A, Maeno Y and Schaper J: The role of the cytoskeleton in heart failure. Cardiovasc Res. 45:273–278. 2000. View Article : Google Scholar : PubMed/NCBI
21	Zhao SH, Gao HQ, Ji X, Wang Y, Liu XJ, You BA, Cui XP and Qiu J: Effect of ouabain on myocardial ultrastructure and cytoskeleton during the development of ventricular hypertrophy. Heart Vessels. 28:101–113. 2013. View Article : Google Scholar : PubMed/NCBI
22	Wu S, Song T, Zhou S, Liu Y, Chen G, Huang N and Liu L: Involvement of Na⁺/H⁺ exchanger 1 in advanced glycation end products-induced proliferation of vascular smooth muscle cell. Biochem Biophys Res Commun. 375:384–389. 2008. View Article : Google Scholar : PubMed/NCBI
23	National Institutes of Health Guide for the Care and Use of Laboratory Animals. National Academies Press. 85-23 revised. Washington, DC: 1996, https://grants.nih.gov/grants/olaw/guide-for-the-care-and-use-of-laboratory-animals.pdf
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
25	Nielsen JM, Kristiansen SB, Nørregaard R, Andersen CL, Denner L, Nielsen TT, Flyvbjerg A and Bøtker HE: Blockage of receptor for advanced glycation end products prevents development of cardiac dysfunction in db/db type 2 diabetic mice. Eur J Heart Fail. 11:638–647. 2009. View Article : Google Scholar : PubMed/NCBI
26	Ma H, Li SY, Xu P, Babcock SA, Dolence EK, Brownlee M, Li J and Ren J: Advanced glycation endproduct (AGE) accumulation and AGE receptor (RAGE) up-regulation contribute to the onset of diabetic cardiomyopathy. J Cell Mol Med. 13:1751–1764. 2009. View Article : Google Scholar : PubMed/NCBI
27	Russo I and Frangogiannis NG: Diabetes-associated cardiac fibrosis: Cellular effectors, molecular mechanisms and therapeutic opportunities. J Mol Cell Cardiol. 90:84–93. 2016. View Article : Google Scholar : PubMed/NCBI
28	Bando YK and Murohara T: Diabetes-related heart failure. Circ J. 78:576–583. 2014. View Article : Google Scholar : PubMed/NCBI
29	Soro-Paavonen A, Zhang WZ, Venardos K, Coughlan MT, Harris E, Tong DC, Brasacchio D, Paavonen K, Chin-Dusting J, Cooper ME, et al: Advanced glycation end-products induce vascular dysfunction via resistance to nitric oxide and suppression of endothelial nitric oxide synthase. J Hypertens. 28:780–788. 2010. View Article : Google Scholar : PubMed/NCBI
30	Vlassara H, Fuh H, Makita Z, Krungkrai S, Cerami A and Bucala R: Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: A model for diabetic and aging complications. Proc Natl Acad Sci USA. 89:12043–12047. 1992; View Article : Google Scholar : PubMed/NCBI
31	Soliman H, Gador A, Lu YH, Lin G, Bankar G and MacLeod KM: Diabetes-induced increased oxidative stress in cardiomyocytes is sustained by a positive feedback loop involving Rho kinase and PKCβ2. Am J Physiol Heart Circ Physiol. 303:H989–H1000. 2012. View Article : Google Scholar : PubMed/NCBI
32	Lin G, Craig GP, Zhang L, Yuen VG, Allard M, McNeill JH and MacLeod KM: Acute inhibition of Rho-kinase improves cardiac contractile function in streptozotocin-diabetic rats. Cardiovasc Res. 75:51–58. 2007. View Article : Google Scholar : PubMed/NCBI
33	Zhou H, Li YJ, Wang M, Zhang LH, Guo BY, Zhao ZS, Meng FL, Deng YG and Wang RY: Involvement of RhoA/ROCK in myocardial fibrosis in a rat model of type 2 diabetes. Acta Pharmacol Sin. 32:999–1008. 2011. View Article : Google Scholar : PubMed/NCBI
34	Lorenzo O, Picatoste B, Ares-Carrasco S, Ramírez E, Egido J and Tuñón J: Potential role of nuclear factor κB in diabetic cardiomyopathy. Mediators Inflamm. 2011:6520972011. View Article : Google Scholar : PubMed/NCBI
35	Thomas CM, Yong QC, Rosa RM, Seqqat R, Gopal S, Casarini DE, Jones WK, Gupta S, Baker KM and Kumar R: Cardiac-specific suppression of NF-κB signaling prevents diabetic cardiomyopathy via inhibition of the renin-angiotensin system. Am J Physiol Heart Circ Physiol. 307:H1036–H1045. 2014. View Article : Google Scholar : PubMed/NCBI