Anti-Inflammatory Effects of Simvastatin in Patients with Chronic Heart Failure

Pinchuk, T. V.; Fedulaev, Yu. N.; Khairetdinova, G. A.; Денисова, Н. Н.; Chura, O. V.; Logunova, I Yu

doi:10.1007/s10517-014-2612-z

Cited by 10 publications

(9 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) are a major class of drugs for treating hypercholesterolaemia (Gbelcova et al, 2013). Alongside hypolipidaemic effects, statins exert antiinflammatory (Pinchuk et al, 2014), antioxidative (Cao et al, 2017), and anti-cancer effects (Sleijfer, van der Gaast, Planting, Stoter, & Verweij, 2005), and they also participate in endothelial regulation and influence cell autophagy and apoptosis (Hwang et al, 2015). However, numerous questions regarding the role of simvastatin in the heart remain unanswered and require further investigation.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial protection by simvastatin against angiotensin II‐mediated heart failure

Hsieh

Hsu

et al. 2019

British J Pharmacology

View full text Add to dashboard Cite

Background and PurposeMitochondrial dysfunction plays a role in the progression of cardiovascular diseases including heart failure. 3‐Hydroxy‐3‐methylglutaryl‐CoA reductase inhibitors (statins), which inhibit ROS synthesis, show cardioprotective effects in chronic heart failure. However, the beneficial role of statins in mitochondrial protection in heart failure remains unclear.Experimental ApproachRats were treated with angiotensin II (1.5 mg·kg−1·day−1) or co‐administered simvastatin (oral, 10 mg·kg−1) for 14 days; and then administration was stopped for the following 14 days. Cardiac structure/function was examined by wheat germ agglutinin staining and echocardiography. Mitochondrial morphology and the numbers of lipid droplets, lysosomes, autophagosomes, and mitophagosomes were determined by transmission electron microscopy. Human cardiomyocytes were stimulated, and intracellular ROS and mitochondrial membrane potential (ΔΨ m) changes were measured by flow cytometry and JC‐1 staining, respectively. Autophagy and mitophagy‐related and mitochondria‐regulated apoptotic proteins were identified by immunohistochemistry and western blotting.Key ResultsSimvastatin significantly reduced ROS production and attenuated the disruption of ΔΨ m. Simvastatin induced the accumulation of lipid droplets to provide energy for maintaining mitochondrial function, promoted autophagy and mitophagy, and inhibited mitochondria‐mediated apoptosis. These findings suggest that mitochondrial protection mediated by simvastatin plays a therapeutic role in heart failure prevention by modulating antioxidant status and promoting energy supplies for autophagy and mitophagy to inhibit mitochondrial damage and cardiomyocyte apoptosis.Conclusion and ImplicationsMitochondria play a key role in mediating heart failure progression. Simvastatin attenuated heart failure, induced by angiotensin II, via mitochondrial protection and might provide a new therapy to prevent heart failure.

show abstract

Section: Introductionmentioning

confidence: 99%

Mitochondrial protection by simvastatin against angiotensin II‐mediated heart failure

Hsieh

Hsu

et al. 2019

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Simvastatin is an angiotensin II receptor inhibitor and is commonly used to treat hyperlipidemia and hypertension. Clinical observation found that taking simvastatin for 20 days significantly reduces the levels of proinflammatory markers interleukin-6 and C-reactive protein in patients with chronic HF 144 . It also induces lipid droplet accumulation, provides energy for maintaining mitochondrial function, promotes mitochondrial autophagy and phagocytosis, and inhibits mitochondrial damage and cardiomyocyte apoptosis 145 .…”

Section: Potential Drugs For Reducing Hf By Regulating Energy Metabolismmentioning

confidence: 98%

Energy metabolism disorders and potential therapeutic drugs in heart failure

Huang

Zhang

et al. 2021

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

Heart failure (HF) is a global public health problem with high morbidity and mortality. A large number of studies have shown that HF is caused by severe energy metabolism disorders, which result in an insufficient heart energy supply. This deficiency causes cardiac pump dysfunction and systemic energy metabolism failure, which determine the development of HF and recovery of heart. Current HF therapy acts by reducing heart rate and cardiac preload and afterload, treating the HF symptomatically or delaying development of the disease. Drugs aimed at cardiac energy metabolism have not yet been developed. In this review, we outline the main characteristics of cardiac energy metabolism in healthy hearts, changes in metabolism during HF, and related pathways and targets of energy metabolism. Finally, we discuss drugs that improve cardiac function via energy metabolism to provide new research ideas for the development and application of drugs for treating HF.

show abstract

“…In a population of 3124 HFpEF patients, Nochioka et al demonstrated that statins could be associated with reduced all‐cause and non‐cardiovascular mortality rates. Another small study documented that statin therapy could reduce inflammatory biomarkers with beneficial effects on diastolic pattern and myocardial relaxation …”

Section: Biomarkers In Heart Failure With Preserved Ejection Fractionmentioning

confidence: 99%

Role of biomarkers in cardiac structure phenotyping in heart failure with preserved ejection fraction: critical appraisal and practical use

D’Elia

Vaduganathan

Gori

et al. 2015

European J of Heart Fail

View full text Add to dashboard Cite

Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome characterized by cardiovascular, metabolic, and pro‐inflammatory diseases associated with advanced age and extracardiac comorbidities. All of these conditions finally lead to impairment of myocardial structure and function. The large phenotypic heterogeneity of HFpEF from pathophysiological underpinnings presents a major hurdle to HFpEF therapy. The new therapeutic approach in HFpEF should be targeted to each HF phenotype, instead of the ‘one‐size‐fits‐all’ approach, which has not been successful in clinical trials. Unless the structural and biological determinants of the failing heart are deeply understood, it will be impossible to appropriately differentiate HFpEF patients, identify subtle myocardial abnormalities, and finally reverse abnormal cardiac function. Based on evidence from endomyocardial biopsies, some of the specific cardiac structural phenotypes to be targeted in HFpEF may be represented by myocyte hypertrophy, interstitial fibrosis, myocardial inflammation associated with oxidative stress, and coronary disease. Once the diagnosis of HFpEF has been established, a potential approach could be to use a panel of biomarkers to identify the main cardiac structural HFpEF phenotypes, guiding towards more appropriate therapeutic strategies. Accordingly, the purpose of this review is to investigate the potential role of biomarkers in identifying different cardiac structural HFpEF phenotypes and to discuss the merits of a biomarker‐guided strategy in HFpEF.

show abstract

Anti-Inflammatory Effects of Simvastatin in Patients with Chronic Heart Failure

Cited by 10 publications

References 8 publications

Mitochondrial protection by simvastatin against angiotensin II‐mediated heart failure

Mitochondrial protection by simvastatin against angiotensin II‐mediated heart failure

Energy metabolism disorders and potential therapeutic drugs in heart failure

Role of biomarkers in cardiac structure phenotyping in heart failure with preserved ejection fraction: critical appraisal and practical use

Contact Info

Product

Resources

About