title: The complex regulation of tanshinone IIA in rats with hypertension-induced left ventricular hypertrophy.
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-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.
authors.affiliation: Department of Cardiovascular Medicine, Central Hospital of Xuzhou, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Pang
authors.affiliation: Department of Cardiovascular Medicine, Central Hospital of Xuzhou, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Cardiovascular Medicine, Central Hospital of Xuzhou, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Ultrasonography, Central Hospital of Xuzhou, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Peng
mesh_terms: D045784:Abietanes / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D005355:Fibrosis; D006334:Heart Function Tests; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013599:Systole / Q000187:drug effects; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D045784:Abietanes; D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C021751:tanshinone; D019716:Tissue Inhibitor of Metalloproteinase-2; D008315:Malondialdehyde; D003094:Collagen; D013482:Superoxide Dismutase; D020778:Matrix Metalloproteinase 2