The complex regulation of tanshinone IIA in rats with hypertension-induced left ventricular hypertrophy
Authors: Hui Pang
Bing Han
Tao Yu
Zhen Peng
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Tanshinone IIA; cardiovascular diseases; hypertension-induced left ventricular hypertrophy; signaling pathways; remodeling
Affiliations: Department of Cardiovascular Medicine, Central Hospital of Xuzhou, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu, China., Department of Ultrasonography, Central Hospital of Xuzhou, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu, China.

Abstract:  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-Œ≤/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. 

Retracted: No

PubPeer comments:
 Several concerns were reported to the journal in 2015, but no action yet. Figure 2A. * Red boxes: The Tan(10) and Tan(15) panels appear to shown an overlap.  , 
 Figure 2D and E. * Blue boxes: The Sham GAPDH panel in Figure 2D looks similar to the Tan(15) GAPDH panel in Figure 2E.  , 
 Figure 4A. * Yellow boxes: In the upper panels, the 5% GS panel appears to show an overlap with the Tan(15) panel. * Green boxes: In the lower panels, the 5% GS panel appears to show an overlap with the Tan(5) panel.  ,