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      The Complex Regulation of Tanshinone IIA in Rats with Hypertension-Induced Left Ventricular Hypertrophy

      1 , * , 1 , 1 , 2

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          Tanshinone IIA has definite protective effects on various cardiovascular diseases. However, in hypertension-induced left ventricular hypertrophy (H-LVH), the signaling pathways of tanshinone IIA in inhibition of remodeling and cardiac dysfunction remain unclear. Two-kidney, one-clip induced hypertensive rats (n = 32) were randomized to receive tanshinone IIA (5, 10, 15 mg/kg per day) or 5% glucose injection (GS). Sham-operated rats (n = 8) received 5%GS as control. Cardiac function and dimensions were assessed by using an echocardiography system. Histological determination of the fibrosis and apoptosis was performed using hematoxylin eosin, Masson’s trichrome and TUNEL staining. Matrix metalloproteinase 2 (MMP2) and tissue inhibitor of matrix metalloproteinases type 2 (TIMP2) protein expressions in rat myocardial tissues were detected by immunohistochemistry. Rat cardiomyocytes were isolated by a Langendorff perfusion method. After 48 h culture, the supernatant and cardiomyocytes were collected to determine the potential related proteins impact on cardiac fibrosis and apoptosis. Compared with the sham rats, the heart tissues of H-LVH (5%GS) group suffered severely from the oxidative damage, apoptosis of cardiomyocytes and extracellular matrix (ECM) deposition. In the H-LVH group, tanshinone IIA treated decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity. Tanshinone IIA inhibited cardiomyocytes apoptosis as confirmed by the reduction of TUNEL positive cardiomyocytes and the down-regulation of Caspase-3 activity and Bax/Bcl-2 ratio. Meanwhile, plasma apelin level increased with down-regulation of APJ receptor. Tanshinone IIA suppressed cardiac fibrosis through regulating the paracrine factors released by cardiomyocytes and the TGF-β/Smads signaling pathway activity. In conclusion, our in vivo study showed that tanshinone IIA could improve heart function by enhancing myocardial contractility, inhibiting ECM deposition, and limiting apoptosis of cardiomyocytes and oxidative damage.

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          Most cited references 48

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                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                19 March 2014
                : 9
                : 3
                [1 ]Department of Cardiovascular Medicine, Central Hospital of Xuzhou, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu, China
                [2 ]Department of Ultrasonography, Central Hospital of Xuzhou, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu, China
                University of Milano, Italy
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: HP. Performed the experiments: ZP. Analyzed the data: TY. Contributed reagents/materials/analysis tools: BH. Wrote the paper: HP.


                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Pages: 9
                This research was supported by the Xuzhou Municipal Bureau of Science and Technology (No. XZZD1020) and Xuzhou Municipal Health Bureau (No. XWJ2011030). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Research Article
                Biology and life sciences
                Cardiovascular Anatomy
                Cell biology
                Signal transduction
                Cell signaling
                Signaling cascades
                Apoptotic signaling cascade
                TGF-beta signaling cascade
                Apoptotic Signaling
                Molecular Cell Biology
                Medicine and Health Sciences
                Cardiovascular Pharmacology
                Heart Failure
                Clinical Medicine
                Vascular Medicine
                Blood Pressure
                Research and Analysis Methods
                Model Organisms
                Animal Models



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