Attenuation of Low Ambient Temperature-Induced Myocardial Hypertrophy by Atorvastatin via Promoting Bcl-2 Expression

Liang, Jing; Yin, Kun; Cao, Xuefeng; Han, Zhenbo; Huang, Qi; Zhang, Lai; Ma, Wanbiao; Ding, Fengzhi; Bi, Chongwei; Feng, Dan; Pan, Zhenwei; Liu, Yu

doi:10.1159/000456111

Cited by 22 publications

(20 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A major intrinsic feature of fibrosis is increased cardiac collagen deposition [26][27][28][29]. In this study, we observed that Aur administration largely reduced the expression of collagen type I in pressure-overloaded hearts and cardiac fibroblasts induced by Ang II treatment, which suggested that blockade of cardiac fibroblast activation is a critical mechanism for Aur-mediated inhibition of the progression to cardiac fibrosis.…”

Section: Discussionmentioning

confidence: 54%

Deubiquitinase Inhibitor Auranofin Attenuated Cardiac Hypertrophy by Blocking NF-κB Activation

Zhang

Liu

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Cardiac hypertrophy is a major outcome and compensatory response of the cardiovascular system to hemodynamic and additional stress responses that ultimately lead to heart failure. Auranofin (Aur) has been used for treating rheumatic arthritis for several decades. Aur is a 19S proteasome-associated deubiquitinase inhibitor, and inhibition of the proteasome is speculated to reverse cardiac hypertrophy. However, the role of the deubiquitinases, especially 19S proteasome-associated deubiquitinases, in the regulation of cardiac remodeling remains poorly understood. The present study investigated the role of Aur in cardiac hypertrophy both in vitro and in vivo. Methods: Male Sprague-Dawley rats underwent abdominal aortic constriction to induce left ventricular hypertrophy. The neonatal rat primary myocardial cell hypertrophy model was induced by Ang II. Echocardiography, hematoxylin-eosin staining, Masson's trichrome staining, immunochemistry, western blot analysis, a cell viability assay, and enzyme-linked immunosorbent assay were performed. Results: Aur significantly reduced the abdominal aortic constriction that led to left ventricular hypertrophy, reduced heart cavity expansion, and functional disorder, and thereby reduced fetal gene expression and attenuated cardiac fibrosis. Furthermore, Aur caused marked accumulation of ubiquitinated proteins and IκBα, as well as inactivation of NF-κB. This phenomenon was confirmed in the neonatal rat primary myocardial cell hypertrophy model. Conclusions: The present study indicated that Aur blocks the development of left ventricular hypertrophy induced by abdominal aortic constriction. This phenomenon might be attributed to inhibition of the 19S proteasome-associated deubiquitinase that can lead to aggregation

show abstract

Section: Discussionmentioning

confidence: 54%

Deubiquitinase Inhibitor Auranofin Attenuated Cardiac Hypertrophy by Blocking NF-κB Activation

Zhang

Liu

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Myocardial apoptosis is one of the characteristics of pathological myocardial hypertrophy and contributes to the transition from compensatory hypertrophy to heart failure [23, 24]. Thus, the protective effect of atorvastatin on hypertrophic myocardium might be at least partly attributed to the inhibition of apoptosis [25]. Although there was no sign of heart failure at the age of 16 weeks in SHR in the present study, the inhibition of apoptosis by atorvastatin also had an important protective effect against the further progress of pathological myocardial hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin Attenuates Myocardial Hypertrophy in Spontaneously Hypertensive Rats via the C/EBPβ/PGC-1α/UCP3 Pathway

Chen¹,

Chang²,

Zhang³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Many clinical and experimental studies have shown that treatment with statins could prevent myocardial hypertrophy and remodeling induced by hypertension and myocardial infarction. But the molecular mechanism was not clear. We aimed to investigate the beneficial effects of atorvastatin on hypertension-induced myocardial hypertrophy and remodeling in spontaneously hypertensive rats (SHR) with the hope of revealing other potential mechanisms or target pathways to interpret the pleiotropic effects of atorvastatin on myocardial hypertrophy. Methods: The male and age-matched animals were randomly divided into three groups: control group (8 WKY), SHR (8 rats) and intervention group (8 SHR). The SHR in intervention group were administered by oral gavage with atorvastatin (suspension in distilled water, 10 mg/Kg once a day) for 6 weeks, and the other two groups were administered by gavage with equal quantity distilled water. Blood pressure of rats was measured every weeks using a standard tail cuff sphygmomanometer. Left ventricular (LV) dimensions were measured from short-axis views of LV under M-mode tracings using Doppler echocardiograph. Cardiomyocyte apoptosis was assessed by the TUNEL assay. The protein expression of C/EBPβ, PGC-1α and UCP3 were detected by immunohistochemistry or Western blot analysis. Results: At the age of 16 weeks, the mean arterial pressure of rats in three groups were 103.6±6.1, 151.8±12.5 and 159.1±6.2 mmHg respectively, and there wasn’t statistically significant difference between the SHR and intervention groups. Staining with Masson’s trichrome demonstrated that the increased interstitial fibrosis of LV and ventricular remodeling in the SHR group were attenuated by atorvastatin treatment. Echocardiography examination exhibited that SHR with atorvastatin treatment showed an LV wall thickness that was obviously lower than that of water-treated SHR. In hypertrophic myocardium, accompanied by increasing C/EBPβ expression and the percentage of TUNEL-positive cells, the expression of Bcl-2/Bax ratio, PGC-1α and UCP3 were reduced, all of which could be abrogated by treatment with atorvastatin for 6 weeks. Conclusion: This study further confirmed that atorvastatin could attenuate myocardial hypertrophy and remodeling in SHR by inhibiting apoptosis and reversing changes in mitochondrial metabolism. The C/EBPβ/PGC-1α/UCP3 signaling pathway might also be important for elucidating the beneficial pleiotropic effects of atorvastatin on myocardial hypertrophy.

show abstract

“…Liang et al indicated that atorvastatin attenuated cardiac hypertrophy under cold exposure. 28 In another study, Wang et al demonstrated that pressure overload-induced right ventricular hypertrophy was reversed by the atorvastatin treatment. 29 Moreover, one study also showed an inhibitory effect of atorvastatin on hypertrophy caused by parathyroid hormone 1-34.…”

Section: Discussionmentioning

confidence: 98%

“…Moreover, in this study, atorvastatin reversed the hypertrophy induced by volume overload and stretch. Liang et al indicated that atorvastatin attenuated cardiac hypertrophy under cold exposure . In another study, Wang et al demonstrated that pressure overload‐induced right ventricular hypertrophy was reversed by the atorvastatin treatment .…”

Section: Discussionmentioning

confidence: 99%

Effect of atorvastatin on cardiomyocyte hypertrophy through suppressing MURC induced by volume overload and cyclic stretch

Cheng¹,

Wang³

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

MURC (muscle‐restricted coiled‐coil protein) is a hypertrophy‐related gene. Hypertrophy can be induced by mechanical stress. The purpose of this research was to investigate the hypothesis that MURC mediates hypertrophy in cardiomyocytes under mechanical stress. We used the in vivo model of an aortocaval shunt (AV shunt) in adult Wistar rats to induce myocardial hypertrophy. We also used the in vitro model of cyclic stretch in rat neonatal cardiomyocytes to clarify MURC expression and the molecular regulation mechanism. The flexible membrane culture plate seeding with cardiomyocytes Cardiomyocytes seeded on a flexible membrane culture plate were stretched by vacuum pressure to 20% of maximum elongation at 60 cycles/min. AV shunt induction enhanced MURC protein expression in the left ventricular myocardium. Treatment with atorvastatin inhibited the hypertrophy induced by the AV shunt. Cyclic stretch markedly enhanced MURC protein and mRNA expression in cardiomyocytes. Addition of extracellular‐signal‐regulated kinase (ERK) inhibitor PD98059, ERK small interfering RNA (siRNA), angiotensin II (Ang II) antibody and atorvastatin before stretch, abolished the induction of MURC protein. An electrophoretic mobility shift assay showed that stretch enhanced the DNA binding activity of serum response factor. Stretch increased but MURC mutant plasmid, ERK siRNA, Ang II antibody and atorvastatin reversed the transcriptional activity of MURC induced by stretch. Adding Ang II to the cardiomyocytes also induced MURC protein expression. MURC siRNA and atorvastatin inhibited the hypertrophic marker and protein synthesis induced by stretch. Treatment with atorvastatin reversed MURC expression and hypertrophy under volume overload and cyclic stretch.

show abstract

Attenuation of Low Ambient Temperature-Induced Myocardial Hypertrophy by Atorvastatin via Promoting Bcl-2 Expression

Cited by 22 publications

References 29 publications

Deubiquitinase Inhibitor Auranofin Attenuated Cardiac Hypertrophy by Blocking NF-κB Activation

Deubiquitinase Inhibitor Auranofin Attenuated Cardiac Hypertrophy by Blocking NF-κB Activation

Atorvastatin Attenuates Myocardial Hypertrophy in Spontaneously Hypertensive Rats via the C/EBPβ/PGC-1α/UCP3 Pathway

Effect of atorvastatin on cardiomyocyte hypertrophy through suppressing MURC induced by volume overload and cyclic stretch

Contact Info

Product

Resources

About