Lipid metabolites and their differential pro-arrhythmic profiles: of importance in the development of a new anti-arrhythmic pharmacology

Shao, Yangzhen; Redfors, Björn; Benoist, David; Gizurarson, Sigfús; Ömerovic, Elmir

doi:10.1007/s11010-014-2060-0

Cited by 3 publications

(2 citation statements)

References 60 publications

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“…Finally, all this information strongly demonstrates the essential role of A1R alone in the process of lipolysis and in the control of plasma NEFA levels, highlighting that drugs designed to decrease the concentration of these lipids could be considered as possible therapeutic mechanism targeting the pathologies associated with increased levels of these lipids (Shao et al, 2014).…”

Section: Accepted Manuscriptmentioning

confidence: 83%

“…However, these agonists have side effects in cells other than adipocytes (e.g., bradycardia in cardiomyocytes) (Bragança et al, 2016). Therefore, drugs designed to decrease the concentration of these lipids could be considered as possible therapeutic targets (Shao et al, 2014). New agonists for A1R should to be developed and probed to delineate the beneficial and adverse effects of the antagonists (Fraser et al, 2003).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Adenosine receptors: Modulators of lipid availability that are controlled by lipid levels

Leiva

Guzmán-Gutiérrez

Contreras-Duarte

et al. 2017

Molecular Aspects of Medicine

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Adenosine as well as agonists and antagonists for the four adenosine receptor subtypes (A1R, A2AR, A2BR and A3R) play a role in several key physiological and pathophysiological processes, including the regulation of vascular tone, thrombosis, immune response, inflammation, and angiogenesis. This review focuses on the adenosine-mediated regulation of lipid availability in the cell and in the systemic circulation as well in humans and animal models. Therefore, adenosine, mainly by acting on A1R, inhibits lipolysis activity, leading to reduction of the circulating fatty acid levels. This nucleoside can also participate in the early development of atherosclerosis by inhibiting the formation of foam cells via stimulation of cholesterol efflux through A2AR expressed on macrophages and reduction of the inflammatory process by activating A2AR and A2BR. Adenosine also appears to modulate intracellular cholesterol availability in Niemann-Pick type C1 disease and Alzheimer disease via A2AR and A3, respectively. Remarkably, the role of adenosine receptors in the regulation of plasma total cholesterol and triglyceride levels has been studied in animal models. Thus, an anti-atherogenic role for A2BR as well as a pro-atherogenic role of A2AR and A1 have been proposed; A3R has not been shown to participate in the control of lipid levels or the development of atherosclerosis. Surprisingly, and despite the role of A2A in the inhibition of foam cell formation among isolated cells, this receptor appears to be pro-atherogenic in mice. Remarkably, the role of adenosine receptors in human dyslipidaemia and atherosclerosis must to be elucidated. Additionally, it has been reported that increased lipid levels impair the effects of adenosine/adenosine receptors in controlling vascular tone, and we speculate on the possibility that this impairment could be due to alterations in the composition of the membrane microdomains where the adenosine receptors are located. Finally, a possible role for adenosine/adenosine receptors in the phenomena of dyslipidaemia in pregnancy has been proposed.

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Section: Accepted Manuscriptmentioning

confidence: 83%

Section: Accepted Manuscriptmentioning

confidence: 99%

Adenosine receptors: Modulators of lipid availability that are controlled by lipid levels

Leiva

Guzmán-Gutiérrez

Contreras-Duarte

et al. 2017

Molecular Aspects of Medicine

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A compound heterozygosity of Tecrl gene confirmed in a catecholaminergic polymorphic ventricular tachycardia family

Xie

Hou

Jiang

et al. 2019

European Journal of Medical Genetics

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Lipidomics, Atrial Conduction, and Body Mass Index

M¹,

Foco

Teumer

et al. 2019

Circ: Genomic and Precision Medicine

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Background: Lipids are increasingly involved in cardiovascular risk prediction as potential proarrhythmic influencers. However, knowledge is limited about the specific mechanisms connecting lipid alterations with atrial conduction. Methods: To shed light on this issue, we conducted a broad assessment of 151 sphingo- and phospholipids, measured using mass spectrometry, for association with atrial conduction, measured by P wave duration (PWD) from standard electrocardiograms, in the MICROS study (Microisolates in South Tyrol) (n=839). Causal pathways involving lipidomics, body mass index (BMI), and PWD were assessed using 2-sample Mendelian randomization analyses based on published genome-wide association studies of lipidomics (n=4034) and BMI (n=734 481), and genetic association analysis of PWD in 5 population-based studies (n=24 236). Results: We identified an association with relative phosphatidylcholine 38:3 (%PC 38:3) concentration, which was replicated in the ORCADES (Orkney Complex Disease Study; n=951), with a pooled association across studies of 2.59 (95% CI, 1.3–3.9; P =1.1×10 −4 ) ms PWD per mol% increase. While being independent of cholesterol, triglycerides, and glucose levels, the %PC 38:3-PWD association was mediated by BMI. Results supported a causal effect of BMI on both PWD ( P =8.3×10 −5 ) and %PC 38:3 ( P =0.014). Conclusions: Increased %PC 38:3 levels are consistently associated with longer PWD, partly because of the confounding effect of BMI. The causal effect of BMI on PWD reinforces evidence of BMI’s involvement into atrial electrical activity.

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Lipid metabolites and their differential pro-arrhythmic profiles: of importance in the development of a new anti-arrhythmic pharmacology

Cited by 3 publications

References 60 publications

Adenosine receptors: Modulators of lipid availability that are controlled by lipid levels

Adenosine receptors: Modulators of lipid availability that are controlled by lipid levels

A compound heterozygosity of Tecrl gene confirmed in a catecholaminergic polymorphic ventricular tachycardia family

Lipidomics, Atrial Conduction, and Body Mass Index

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