Atorvastatin Slows the Progression of Cardiac Remodeling in Mice with Pressure Overload and Inhibits Epidermal Growth Factor Receptor Activation

Liao, Yulin; Zhao, Hui; Ogai, Akiko; Kato, Hisakazu; Asakura, Masanori; Kim, Jiyoong; Asanuma, Hiroshi; Minamino, Tetsuo; Takashima, Seiji; Kitakaze, Masafumi

doi:10.1291/hypres.31.335

Cited by 29 publications

(23 citation statements)

References 42 publications

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“…ADAM-12 is pathologically expressed in the heart during the development and progression of cardiac hypertrophy, parallel with other developmental and fetal genes such as α-skeletal actin and β-myosin heavy chain [22]. Agonist activation of ADAM-12 is thought to mediate the development of cardiac hypertrophy, as pharmacological ADAM-12 inhibition attenuates cardiac hypertrophy but causes no attenuation of the severity of the hypertension [96,97]. In response to GPCR agonists and pressure overload, ADAM-12 sheds HB-EGF in the myocardium promoting the development of cardiac hypertrophy [96,97].…”

Section: Mmps and Adams In Models Of Hypertensive Cardiac Diseasementioning

confidence: 99%

“…Agonist activation of ADAM-12 is thought to mediate the development of cardiac hypertrophy, as pharmacological ADAM-12 inhibition attenuates cardiac hypertrophy but causes no attenuation of the severity of the hypertension [96,97]. In response to GPCR agonists and pressure overload, ADAM-12 sheds HB-EGF in the myocardium promoting the development of cardiac hypertrophy [96,97]. ADAM-12 also cleaves insulin-like growth factor binding protein, releasing insulin-like growth factor which then activates the insulin-like growth factor receptor, potentially contributing further to hypertrophic growth in the heart [98].…”

Section: Mmps and Adams In Models Of Hypertensive Cardiac Diseasementioning

confidence: 99%

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Insights into the Activity, Differential Expression, Mutual Regulation, and Functions of Matrix Metalloproteinases and A Disintegrin and Metalloproteinases in Hypertension and Cardiac Disease

Berry

Bosonea²,

Wang³

et al. 2012

J Vasc Res

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Hypertensive cardiac disease is a major cause of death worldwide. Causative factors of hypertension include environmental stressors, genetic predisposition, and common morbidities of lipid metabolism such as obesity and diabetes. These factors pathologically elevate the systemic production of vasoconstrictive G-protein-coupled receptor agonists. Pathological concentrations of these agonists upregulate the gene expression and proteolytic activity of matrix metalloproteinases (MMPs) and A disintegrin and metalloproteinases (ADAMs). Among the metalloproteinases that act in concert with other mediators to elevate the systemic blood pressure and to modulate the development of cardiovascular hypertrophy and fibrosis processes are MMP-2, MMP-7, ADAM-12, and ADAM-17. This review offers insights into the activity, differential expression, mutual regulation, and functions of these metalloproteinases. We further review evidence linking them to transcription factors, carrier proteins, and receptors for lipids. The emerging links between metalloproteinases and lipids are intriguing and suggest new therapeutic targets in hypertensive cardiac disease.

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Section: Mmps and Adams In Models Of Hypertensive Cardiac Diseasementioning

confidence: 99%

Section: Mmps and Adams In Models Of Hypertensive Cardiac Diseasementioning

confidence: 99%

Insights into the Activity, Differential Expression, Mutual Regulation, and Functions of Matrix Metalloproteinases and A Disintegrin and Metalloproteinases in Hypertension and Cardiac Disease

Berry

Bosonea²,

Wang³

et al. 2012

J Vasc Res

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show abstract

“…Slowing or reversing cardiac remodeling is an important therapeutic goal in patients with CHF. Studies have shown that hydroxymethylglutaryl-CoA reductase inhibitors (statins) attenuate cardiac remodeling in animals or patients with either ischemic or non-ischemic CHF (1)(2)(3)(4)(5)(6)(7), suggesting that statin therapy may be a potential novel approach for CHF. A meta-analysis of randomized controlled trials showed that treatment with statins in CHF patients attenuates cardiac remodeling and relives clinical symptoms (8).…”

Section: Introductionmentioning

confidence: 99%

Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway

Cao

Zeng

Wang

et al. 2013

Molecular Medicine Reports

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Abstract. Tumor necrosis factor-α (TNF-α) and c-Jun N-terminal kinases (JNKs) are known to be associated with apoptosis and are important in cardiac remodeling. It remains to be determined whether statins inhibit cardiac remodeling through interfering with TNF-α-JNK-related signaling pathways. This study was designed to investigate the effect of pravastatin on the progression of hypertrophy to heart failure in transverse aortic constriction (TAC) and the associations with TNF-α-JNK signaling. Either pravastatin (5 or 20 mg/kg/day) or vehicle was orally administered to male C57BL/6J mice with TAC. Cardiac remodeling and left ventricular hemodynamics, as well as JNK-dependent apoptotic signals were analyzed 4 weeks following TAC. Neonatal rat cardiomyocytes were cultured to investigate the effect of pravastatin on TNF-α-induced JNK-related apoptotic signals. Notably, pravastatin reduced the heart/body weight and lung/body weight ratios. In addition, a decrease of left ventricular (LV) echocardiographic dimensions, an increase of LV fractional shortening and diastolic index, a reduction of JNK activity, caspase-12 and Bax were observed in the pravastatin-treated groups. The TNF-α-induced phosphorylation of JNK and upregulation of caspase-12 and Bax in cultured cardiomyocytes was inhibited by pravastatin. These results indicated that pravastatin attenuates cardiac remodeling by inhibiting JNK-dependent pro-apoptotic signaling.

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“…In response to a number of inhibitory (stress) signals, the activity of eIF2B, and thus the rate of assembly of ternary complex, is reduced, which can lead to the repression of global rates of protein synthesis. Intriguingly, there have been a number of reports indicating that statins attenuate or prevent cardiac hypertrophy (5,20,24,43). In this context, it is important to note that eIF2B⑀ is implicated in ␤-adrenergic mediated cardiomyocyte hypertrophy (12) and that overexpression of eIF2B⑀ increases GEF activity and/or protein synthesis in a number of different cell types (3,12,35,40,42).…”

mentioning

confidence: 99%

Simvastatin represses protein synthesis in the muscle-derived C₂C₁₂cell line with a concomitant reduction in eukaryotic initiation factor 2B expression

Tuckow

Jefferson

Kimball

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Tuckow AP, Jefferson SJ, Kimball SR, Jefferson LS. Simvastatin represses protein synthesis in the muscle-derived C 2C12 cell line with a concomitant reduction in eukaryotic initiation factor 2B expression. Am J Physiol Endocrinol Metab 300: E564 -E570, 2011. First published January 11, 2011; doi:10.1152/ajpendo.00383.2010Statins are a widely prescribed class of cholesterol lowering drugs whose use is frequently associated with muscle-related ailments. A number of mechanisms have been implicated in statin-induced myotoxicity including alterations in both protein synthesis and protein degradation. The objective of the present study was to explore the mechanism(s) contributing to the statin-induced reduction in protein synthesis in the muscle-derived C 2C12 cell line. Cells were treated with 10 M simvastatin or vehicle alone for 24 h in 1% serum. Cells exposed to simvastatin exhibited reduced rates of protein synthesis, as evidenced by [35 S]methionine and [ 35 S]cysteine incorporation into protein. The reduction in protein synthesis occurred with a concomitant decrease in expression and activity of eukaryotic initiation factor 2B (eIF2B), a regulated and rate-controlling guanine nucleotide exchange factor known to affect global rates of protein synthesis. The reductions in protein synthesis and eIF2B expression were prevented by coincubation with mevalonate. Simvastatin treatment also resulted in a proteasome-sensitive reduction in the protein expression of all the subunits of the eIF2B heteropentameric complex. Finally, increased phosphorylation of the catalytic ⑀-subunit at Ser 535 was observed, an event consistent with an observed reduction in eIF2B activity. These results suggest that repression of eIF2B expression and activity may contribute, at least in part, to the statin-induced reduction in protein synthesis.messenger RNA translation; 3-hydroxy-3-methylglutaryl coenzyme A-reductase; myoblasts; myotubes STATINS [3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors] are a widely prescribed and effective class of lipid lowering drugs that have demonstrated enormous clinical benefit not only for reducing cardiovascular risk (26) but also for several additional and unexpected pleiotropic benefits (e.g., anti-inflammatory and immunomodulatory effects) (10, 23). One of the less desirable effects of statin use is the incidence of myopathies ranging from complaints of muscle pain and weakness (i.e., myalgia) to the most severe case of rhabdomyolysis, which is rare but can be fatal (2, 34). The mechanisms implicated in the myotoxic effects of statins are still poorly understood. Recently, statins have been shown to upregulate the "atrogenes" MAFbx and/or MuRF-1 in human, zebrafish, and rodent skeletal muscle, which may contribute to increased rates of muscle proteolysis (4,11,21). In addition to enhanced proteolysis, other groups have reported decrements in the rate of protein synthesis in embryonic chick cardiomyocytes (28) and rat primary myocytes (8, 22), although the mechanism for the repression...

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Atorvastatin Slows the Progression of Cardiac Remodeling in Mice with Pressure Overload and Inhibits Epidermal Growth Factor Receptor Activation

Abstract: The aim of this study was to investigate whether atorvastatin inhibits epidermal growth factor receptor

Cited by 29 publications

References 42 publications

Insights into the Activity, Differential Expression, Mutual Regulation, and Functions of Matrix Metalloproteinases and A Disintegrin and Metalloproteinases in Hypertension and Cardiac Disease

Insights into the Activity, Differential Expression, Mutual Regulation, and Functions of Matrix Metalloproteinases and A Disintegrin and Metalloproteinases in Hypertension and Cardiac Disease

Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway

Simvastatin represses protein synthesis in the muscle-derived C₂C₁₂cell line with a concomitant reduction in eukaryotic initiation factor 2B expression

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Atorvastatin Slows the Progression of Cardiac Remodeling in Mice with Pressure Overload and Inhibits Epidermal Growth Factor Receptor Activation

Abstract: The aim of this study was to investigate whether atorvastatin inhibits epidermal growth factor receptor

Cited by 29 publications

References 42 publications

Insights into the Activity, Differential Expression, Mutual Regulation, and Functions of Matrix Metalloproteinases and A Disintegrin and Metalloproteinases in Hypertension and Cardiac Disease

Insights into the Activity, Differential Expression, Mutual Regulation, and Functions of Matrix Metalloproteinases and A Disintegrin and Metalloproteinases in Hypertension and Cardiac Disease

Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway

Simvastatin represses protein synthesis in the muscle-derived C2C12cell line with a concomitant reduction in eukaryotic initiation factor 2B expression

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Simvastatin represses protein synthesis in the muscle-derived C₂C₁₂cell line with a concomitant reduction in eukaryotic initiation factor 2B expression