Atorvastatin reduces cardiac and adipose tissue inflammation in rats with metabolic syndrome

Yamada, Yoshio; Takeuchi, Sawako; Yoneda, Mamoru; Ito, Shogo; Sano, Yusuke; Nagasawa, Kai; Matsuura, Natsumi; Uchinaka, Ayako; Murohara, Toyoaki; Nagata, Kazuya

doi:10.1016/j.ijcard.2017.04.103

Cited by 38 publications

(26 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, clinical trials using resveratrol as an anti-obesity agent have yielded conflicting and less convincing results and further large-scale RCTs are needed before definite conclusions of its effectiveness in obesity in general, and OSA populations specifically, can be drawn. Promising amelioration of adipose tissue inflammation has also been demonstrated with statin therapy possibly through inhibition of nuclear factor-κB activity and activation of the AMP-activated protein kinase leading to improved insulin sensitivity [95]. Following this approach, an RCT of statin therapy versus CPAP in patients with OSA investigating its impact on cellular damage in subcutaneous adipose tissue is currently underway at the Mayo Clinic (Rochester, MN, USA) and results may help identify the role of statins in adipose tissue dysfunction of patients with OSA.…”

Section: Current Limitations and Future Directivesmentioning

confidence: 99%

Adipose tissue as a key player in obstructive sleep apnoea

et al. 2019

View full text Add to dashboard Cite

Obstructive sleep apnoea (OSA) is a major health concern worldwide and adversely affects multiple organs and systems. OSA is associated with obesity in >60% of cases and is independently linked with the development of numerous comorbidities including hypertension, arrhythmia, stroke, coronary heart disease and metabolic dysfunction. The complex interaction between these conditions has a significant impact on patient care and mortality. The pathophysiology of cardiometabolic complications in OSA is still incompletely understood; however, the particular form of intermittent hypoxia (IH) observed in OSA, with repetitive short cycles of desaturation and re-oxygenation, probably plays a pivotal role. There is fast growing evidence that IH mediates some of its detrimental effects through adipose tissue inflammation and dysfunction. This article aims to summarise the effects of IH on adipose tissue in experimental models in a comprehensive way. Data from well-designed controlled trials are also reported with the final goal of proposing new avenues for improving phenotyping and personalised care in OSA.

show abstract

Section: Current Limitations and Future Directivesmentioning

confidence: 99%

Adipose tissue as a key player in obstructive sleep apnoea

et al. 2019

View full text Add to dashboard Cite

show abstract

Section: Therapeutic Challenges In Patients With a Metabolic Disordermentioning

confidence: 99%

“…Statins are commonly used in patients with obesity and type 2 diabetes to prevent atherosclerotic events, but they have striking effects in lessening epicardial adipocyte mass and inflammation, [98][99][100][101] and thereby preventing fibrosis in the underlying myocardium. 102,103 This anti-inflammatory action may explain why statins ameliorate the development of an atrial myopathy in experimentally induced cardiac stress and in patients with AF. [104][105][106] In randomized controlled trials (RCTs), statins reduced the incidence of new-onset as well as recurrent AF; 107-109 their use is also associated with a decrease in AF-related thromboembolic events.…”

Section: Statinsmentioning

confidence: 99%

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

Packer

2019

European J of Heart Fail

View full text Add to dashboard Cite

Obesity and diabetes can lead to heart failure with preserved ejection fraction (HFpEF), potentially because they both cause expansion and inflammation of epicardial adipose tissue and thus lead to microvascular dysfunction and fibrosis of the underlying left ventricle. The same process also causes an atrial myopathy, which is clinically evident as atrial fibrillation (AF); thus, AF may be the first manifestation of HFpEF. Many patients with apparently isolated AF have latent HFpEF or subsequently develop HFpEF. Most patients with obesity or diabetes who have AF and exercise intolerance have increased left atrial pressures at rest or during exercise, even in the absence of diagnosed HFpEF. Among patients with AF, those who also have latent HFpEF have increased risk for systemic thromboembolism and death. The identification of HFpEF in patients with obesity or diabetes alters the risk‐to‐benefit relationship of commonly prescribed treatments. Bariatric surgery and statins can ameliorate AF and reduce the risk for HFpEF. Conversely, antihyperglycaemic drugs that promote adipogenesis or cause sodium retention (insulin and thiazolidinediones) may increase the risk for heart failure in patients with an underlying ventricular myopathy. Patients with obesity and diabetes who undergo catheter ablation for AF are at increased risk for AF recurrence and for post‐ablation increases in pulmonary venous pressures and worsening heart failure, especially if HFpEF coexists. Therefore, AF may be the earliest indicator of HFpEF in patients with obesity or type 2 diabetes, and recognition of HFpEF alters the management of these patients.

show abstract

“…Interestingly, independent of their effects on blood cholesterol or lipoproteins, statins act to reduce the quantity of epicardial adipose tissue and decrease its pro‐inflammatory characteristics . Researchers have long postulated that this class of drugs reduces the risk of coronary atherosclerotic ischaemic events by virtue of an anti‐inflammatory effect.…”

Section: Anti‐inflammatory Effects Of Statins In Heart Failurementioning

confidence: 99%

Are the effects of drugs to prevent and to treat heart failure always concordant? The statin paradox and its implications for understanding the actions of antidiabetic medications

Packer

2018

European J of Heart Fail

View full text Add to dashboard Cite

Most treatments for chronic heart failure are effective both in preventing its onset and reducing its progression. However, statins prevent the development of heart failure, but they do not decrease morbidity and mortality in those with established heart failure. This apparent discordance cannot be explained by an effect to prevent interval myocardial infarctions. Instead, it seems that the disease that statins were preventing in trials of patients with a metabolic disorder was different from the disease that they were treating in trials of chronic heart failure. The most common phenotype of heart failure in patients with obesity and diabetes is heart failure with a preserved ejection fraction (HFpEF). In this disorder, the anti-inflammatory effects of statins might ameliorate myocardial fibrosis and cardiac filling abnormalities, but these actions may have little relevance to patients with heart failure and a reduced ejection fraction (HFrEF), whose primary derangement is cardiomyocyte loss and stretch. These distinctions may explain why statins were ineffective in trials that focused on HFrEF, but have been reported to produce favourable effects in observational studies of HFpEF. Similarly, selective cytokine antagonists were ineffective in HFrEF, but have been associated with benefits in HFpEF. These observations may have important implications for our understanding of the effects of antihyperglycaemic medications. Glucagon-like peptide-1 receptor agonists have had neutral effects on heart failure events in people at risk for HFpEF, but have exerted deleterious actions in HFrEF. Similarly, sodium-glucose co-transporter 2 inhibitors, which exert anti-inflammatory effects and reduce heart failure events in patients who are prone to HFpEF, may not be effective in HFrEF. The distinctions between HFrEF and HFpEF may explain why the effects of drugs on heart failure events in diabetes trials may not be relevant to their use in patients with systolic dysfunction.

show abstract

Atorvastatin reduces cardiac and adipose tissue inflammation in rats with metabolic syndrome

Cited by 38 publications

References 43 publications

Adipose tissue as a key player in obstructive sleep apnoea

Adipose tissue as a key player in obstructive sleep apnoea

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

Are the effects of drugs to prevent and to treat heart failure always concordant? The statin paradox and its implications for understanding the actions of antidiabetic medications

Contact Info

Product

Resources

About