The Ginsenoside Rg1 Prevents Transverse Aortic Constriction–Induced Left Ventricular Hypertrophy and Cardiac Dysfunction by Inhibiting Fibrosis and Enhancing Angiogenesis

2013 ◽  
Vol 62 (1) ◽  
pp. 50-57 ◽  
Author(s):  
Yao-Jun Zhang ◽  
Xin-Lei Zhang ◽  
Ming-Hui Li ◽  
Javaid Iqbal ◽  
Christos V. Bourantas ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Cardiac Dysfunction ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Ginsenoside Rg1 ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction

scholarly journals Platelet volume indices are associated with systolic and diastolic cardiac dysfunction, and left ventricular hypertrophy

2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Shu-ichi Fujita ◽  
Yoshihiro Takeda ◽  
Shun Kizawa ◽  
Takahide Ito ◽  
Kazushi Sakane ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Cardiac Dysfunction ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Platelet Volume

scholarly journals Left Ventricular Hypertrophy Increases Susceptibility to Bupivacaine-induced Cardiotoxicity through Overexpression of Transient Receptor Potential Canonical Channels in Rats

2020 ◽  
Vol 133 (5) ◽  
pp. 1077-1092
Author(s):  
Hideki Hino ◽  
Tadashi Matsuura ◽  
Miyuki Kuno ◽  
Kotaro Hori ◽  
Shogo Tsujikawa ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Left Ventricular ◽  
Sodium Ion ◽  
Trpc Channels ◽  
Aortic Constriction ◽  
Transient Receptor ◽  
Underlying Mechanisms

Background Local anesthetics, particularly potent long acting ones such as bupivacaine, can cause cardiotoxicity by inhibiting sodium ion channels; however, the impact of left ventricular hypertrophy on the cardiotoxicity and the underlying mechanisms remain undetermined. Transient receptor potential canonical (TRPC) channels are upregulated in left ventricular hypertrophy. Some transient receptor potential channel subtypes have been reported to pass relatively large cations, including protonated local anesthetics; this is known as the “pore phenomenon.” The authors hypothesized that bupivacaine-induced cardiotoxicity is more severe in left ventricular hypertrophy due to upregulated TRPC channels. Methods The authors used a modified transverse aortic constriction model as a left ventricular hypertrophy. Cardiotoxicity caused by bupivacaine was compared between sham and aortic constriction male rats, and the underlying mechanisms were investigated by recording sodium ion channel currents and immunocytochemistry of TRPC protein in cardiomyocytes. Results The time to cardiac arrest by bupivacaine was shorter in aortic constriction rats (n =11) than in sham rats (n = 12) (mean ± SD, 1,302 ± 324 s vs. 1,034 ± 211 s; P = 0.030), regardless of its lower plasma concentration. The half-maximal inhibitory concentrations of bupivacaine toward sodium ion currents were 4.5 and 4.3 μM, which decreased to 3.9 and 2.6 μM in sham and aortic constriction rats, respectively, upon coapplication of 1-oleoyl-2-acetyl-sn-glycerol, a TRPC3 channel activator. In both groups, sodium ion currents were unaffected by QX-314, a positively charged lidocaine derivative, that hardly permeates the cell membrane, but was significantly decreased with QX-314 and 1-oleoyl-2-acetyl-sn-glycerol coapplication (sham: 79 ± 10% of control; P = 0.004; aortic constriction: 47± 27% of control; P = 0.020; n = 5 cells per group). Effects of 1-oleoyl-2-acetyl-sn-glycerol were antagonized by a specific TRPC3 channel inhibitor. Conclusions Left ventricular hypertrophy exacerbated bupivacaine-induced cardiotoxicity, which could be a consequence of the “pore phenomenon” of TRPC3 channels upregulated in left ventricular hypertrophy. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That New

Effect of prophylactic digitalization on the development of myocardial hypertrophy

1977 ◽  
Vol 233 (5) ◽  
pp. H600-H604
Author(s):  
A. F. Cutilletta ◽  
M. Rudnik ◽  
R. A. Arcilla ◽  
R. Straube
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Flow Velocity ◽  
Ventricular Hypertrophy ◽  
Peak Flow ◽  
Myocardial Hypertrophy ◽  
Left Ventricular ◽  
Heart Weight ◽  
Aortic Constriction ◽  
Flow Acceleration ◽  
Peak Flow Velocity

The effect of prophylactic digitalization on the development of left ventricular hypertrophy was studied in adult rats. Digitoxin, 0.1 mg/100 g body wt or solvent was given daily for 1 wk prior to either aortic constriction or sham operation and was continued until the animals were killed, either 1 or 4 wk after surgery. A hemodynamic study was done in those animals killed 1 wk after surgery; hearts of all animals were examined for evidence of myocardial hypertrophy. Constriction of the ascending aorta had no significant effect on cardiac output but did reduce peak flow velocity and flow acceleration. An increase in left ventricular mass, RNA, and hydroxyproline was found in the animals with aortic constriction. Digitoxin treatment did not alter peak flow velocity or flow acceleration, but did significantly increase isovolumic (dP/dt)P-1. Digitoxin had no effect on body weight, heart weight, RNA, or hydroxyproline in either the sham-operated animals or in the animals with aortic constriction. Therefore, despite plasma digitoxin levels sufficient to affect myocardial contractility, left ventricular hypertrophy still developed after aortic constriction.

scholarly journals ADAMTS16 activates latent TGF-β, accentuating fibrosis and dysfunction of the pressure-overloaded heart

2019 ◽  
Author(s):  
Yufeng Yao ◽  
Changqing Hu ◽  
Qixue Song ◽  
Yong Li ◽  
Xingwen Da ◽  
...  
Keyword(s):  
Ventricular Hypertrophy ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Neutralizing Antibody ◽  
Left Ventricular ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Ecm Proteins ◽  
Ecm Degradation

Abstract Aims Cardiac fibrosis is a major cause of heart failure (HF), and mediated by the differentiation of cardiac fibroblasts into myofibroblasts. However, limited tools are available to block cardiac fibrosis. ADAMTS16 is a member of the ADAMTS superfamily of extracellular protease enzymes involved in extracellular matrix (ECM) degradation and remodelling. In this study, we aimed to establish ADAMTS16 as a key regulator of cardiac fibrosis. Methods and results Western blot and qRT–PCR analyses demonstrated that ADAMTS16 was significantly up-regulated in mice with transverse aortic constriction (TAC) associated with left ventricular hypertrophy and HF, which was correlated with increased expression of Mmp2, Mmp9, Col1a1, and Col3a1. Overexpression of ADAMTS16 accelerated the AngII-induced activation of cardiac fibroblasts into myofibroblasts. Protein structural analysis and co-immunoprecipitation revealed that ADAMTS16 interacted with the latency-associated peptide (LAP)-transforming growth factor (TGF)-β via a RRFR motif. Overexpression of ADAMTS16 induced the activation of TGF-β in cardiac fibroblasts; however, the effects were blocked by a mutation of the RRFR motif to IIFI, knockdown of Adamts16 expression, or a TGF-β-neutralizing antibody (ΝAb). The RRFR tetrapeptide, but not control IIFI peptide, blocked the interaction between ADAMTS16 and LAP-TGF-β, and accelerated the activation of TGF-β in cardiac fibroblasts. In TAC mice, the RRFR tetrapeptide aggravated cardiac fibrosis and hypertrophy by up-regulation of ECM proteins, activation of TGF-β, and increased SMAD2/SMAD3 signalling, however, the effects were blocked by TGF-β-NAb. Conclusion ADAMTS16 promotes cardiac fibrosis, cardiac hypertrophy, and HF by facilitating cardiac fibroblasts activation via interacting with and activating LAP-TGF-β signalling. The RRFR motif of ADAMTS16 disrupts the interaction between ADAMTS16 and LAP-TGF-β, activates TGF-β, and aggravated cardiac fibrosis and hypertrophy. This study identifies a novel regulator of TGF-β signalling and cardiac fibrosis, and provides a new target for the development of therapeutic treatment of cardiac fibrosis and HF.

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