High‐density lipoprotein protects cardiomyocytes from oxidative stress via the <scp>PI</scp>3K/<scp>mTOR</scp> signaling pathway

Nagao, Manabu; Toh, Ryuji; Irino, Yasuhiro; Nakajima, Hideto; Oshita, Toshihiko; Tsuda, S.; Hara, Tetsuya; Shinohara, Masakazu; Ishida, Tatsuro; Hirata, Ken–ichi

doi:10.1002/2211-5463.12279

Cited by 9 publications

(7 citation statements)

References 40 publications

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“…In addition, several studies have identified mTOR as an important regulator of cardiac adaptation because its overexpression is protective in pressure-overloaded mouse hearts 47 , 48 ) and its conditional knockout in murine heart causes cardiac dysfunction 49 ) . We demonstrated that HDL activated downstream effectors of mTOR signaling, which played anti-apoptotic roles under oxidative stress, may contribute to cardioprotection 45 ) .…”

Section: Hdl Protects Cardiomyocytes Against Oxidative Stressmentioning

confidence: 89%

“…We recently reported that HDL treatment improved cardiomyocyte viability under oxidative stress through the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway 45 ) . mTOR belongs to the PI3K-related kinase family and critically regulates protein synthesis, cell survival, growth, and proliferation 46 ) .…”

Section: Hdl Protects Cardiomyocytes Against Oxidative Stressmentioning

confidence: 99%

“…1B ). In addition, we have revealed that HDL treatment improves cardiomyocyte viability under oxidative stress and that the PI3K/mTOR signaling pathway mediates these effects 45 ) . In this study, we demonstrated that HDL treatment increased phosphorylation of the ribosomal protein S6 kinase (S6K) and BCL2-associated agonist of cell death (BAD) under oxidative stress via PI3K/mTOR.…”

Section: Hdl Protects Cardiomyocytes By Activating Beneficial Signal mentioning

confidence: 99%

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Cardioprotective Effects of High-Density Lipoprotein Beyond its Anti-Atherogenic Action

Nagao

Nakajima

Toh

et al. 2018

J Atheroscler Thromb

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High-density lipoprotein cholesterol (HDL-C) has been identified as a powerful independent negative predictor of cardiovascular disease. The beneficial effect of HDL is largely attributable to its key role in reverse cholesterol transport, whereby excess cholesterol in the peripheral tissues is transported to the liver, reducing the atherosclerotic burden. However, mounting evidence indicates that HDL also has pleiotropic properties, such as anti-inflammatory, anti-oxidative, and vasodilatory properties, which may contribute in reducing the incidence of heart failure. Actually, previous data from clinical and experimental studies have suggested that HDL exerts cardioprotective effects irrespective of the presence/absence of coronary artery disease. This review summarizes the currently available evidence regarding beneficial effects of HDL on the heart beyond its anti-atherogenic property. Understanding the mechanisms of cardiac protection by HDL will provide new insight into the underlying mechanism and therapeutic strategy for heart failure.

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Section: Hdl Protects Cardiomyocytes Against Oxidative Stressmentioning

confidence: 89%

Section: Hdl Protects Cardiomyocytes Against Oxidative Stressmentioning

confidence: 99%

Section: Hdl Protects Cardiomyocytes By Activating Beneficial Signal mentioning

confidence: 99%

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Cardioprotective Effects of High-Density Lipoprotein Beyond its Anti-Atherogenic Action

Nagao

Nakajima

Toh

et al. 2018

J Atheroscler Thromb

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show abstract

“…In this regard, higher TG level can be viewed as a remote circulating marker of failure in buffering excessive TG from saturated VAT capacity. Conversely, recent molecular evidence has also indicated that HDL can resist oxidative stress and protect cardiomyocytes 30 by serving as a scavenger to reverse imbalanced lipid/energy metabolism and likely provides key beneficial regulatory effects via neurohormonal inactivation 31 . In aggregate, we speculated that both TG and HDL may therefore serve as markers or play essential roles in regulating myocardial homeostasis and functions through their remote effects.…”

Section: Discussionmentioning

confidence: 87%

Associations of region‐specific visceral adiposity with subclinical atrial dysfunction and outcomes of heart failure

et al. 2020

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Aims Excessive visceral adiposity (VAT) plays an essential role in metabolic derangements with those close to heart further mediates myocardial homeostasis. The disparate biological links between region-specific VAT and cardiometabolic profiles as mediators influencing atrial kinetics remain unexplored. Methods and results Among 1326 asymptomatic individuals, region-specific VAT including peri-aortic root fat (PARF) and total pericardial fat (PCF) of cardiac region, together with thoracic peri-aortic adipose tissue (TAT), was assessed using multiple-detector computed tomography. VAT measures were related to functional left atrial (LA) metrics assessed by speckle-tracking algorithm and clinical outcomes of atrial fibrillation (AF) and heart failure (HF). Multivariate linear regression models incorporating body fat, metabolic syndrome, and E/TDI-e' consistently demonstrated independent associations of larger PARF/PCF with peak atrial longitudinal systolic strain (PALS) reduction, higher LA stiffness, and worsened strain rate components; instead, TAT was independently associated with cardiometabolic profiles. PARF rather than PCF or TAT conferred independent prognostic values for incident AF/HF by multivariate Cox regression (adjusted hazard ratio: 1.56, 95% confidence interval: 1.17-2.08, P = 0.002) during a median of 1790 days (interquartile range: 25th to 75th: 1440-1927 days) of follow-up, with subjects categorized into worst PALS and largest VAT tertiles demonstrating highest events (all log-rank P < 0.001). Mediation analysis showed that higher triglyceride and lower high-density lipoproteins may serve as intermediary factors for effects between VAT and LA functional metrics, with lesser role by glucose level. Conclusions Visceral adiposity surrounding atrial region was tightly associated with subclinical atrial dysfunction and incident AF or HF beyond metabolic factors. Instead, peri-aortic adiposity may mediate their toxic effects mainly through circulating cardiometabolic profiles.

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“…FADS1, INSIG1, and LDLR are regulated through SREBP2 pathway likely as a result of the reduction of the cellular cholesterol content. HDL particles may also affect on basic mediators regulating not only lipid biosynthesis but other anabolic processes (Nagao et al, 2017) as well as maintenance and repair reactions (Kimura et al, 2010). Target of rapamycin (mTOR), central mediator of anabolic processes including activation of SREBPs with further lipid biosynthesis, is involved in the induction of trained immunity (Cheng et al, 2014).…”

Section: Monocyte Activatability and Lipid Profilementioning

confidence: 99%

Trained Circulating Monocytes in Atherosclerosis: Ex Vivo Model Approach

et al. 2019

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Inflammation is one of the key processes in the pathogenesis of atherosclerosis. Numerous studies are focused on the local inflammatory processes associated with atherosclerotic plaque initiation and progression. However, changes in the activation state of circulating monocytes, the main components of the innate immunity, may precede the local events. In this article, we discuss tolerance, which results in decreased ability of monocytes to be activated by pathogens and other stimuli, and training, the ability of monocyte to potentiate the response to pathological stimuli, and their relation to atherosclerosis. We also present previously unpublished results of the experiments that our group performed with monocytes/macrophages isolated from atherosclerosis patients. Our data allow assuming the existence of relationship between the formation of monocyte training and the degree of atherosclerosis progression. The suppression of trained immunity ex vivo seems to be a perspective model for searching anti-atherogenic drugs.

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High‐density lipoprotein protects cardiomyocytes from oxidative stress via the PI3K/mTOR signaling pathway

Cited by 9 publications

References 40 publications

Cardioprotective Effects of High-Density Lipoprotein Beyond its Anti-Atherogenic Action

Cardioprotective Effects of High-Density Lipoprotein Beyond its Anti-Atherogenic Action

Associations of region‐specific visceral adiposity with subclinical atrial dysfunction and outcomes of heart failure

Trained Circulating Monocytes in Atherosclerosis: Ex Vivo Model Approach

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