Association of polymorphisms in the endocannabinoid system genes with myocardial infarction and plasma cholesterol levels

Chmelíková, Monika; Pácal, Lukáš; Špinarová, Lenka; Vašků, Anna

doi:10.5507/bp.2014.043

Cited by 6 publications

(7 citation statements)

References 27 publications

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“…When FAAH was knocked out and endocannabinoid contents were increased in the ventricle, the mice experienced alleviated age-related cardiac injury [40]. Moreover, a case-control study found a role for allele A of the FAAH 385 variant as a risk factor for myocardial infarction [41]. Our study found that the selective FAAH inhibitor URB597 and reuptake inhibitor VDM11 were cardiomyocyte protective against H/R (Figure 4) which also supported this notion.…”

Section: Discussionsupporting

confidence: 79%

Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment‐Induced Cardioprotection against Ischemia‐Reperfusion Injury in Rats

Sun

Lü

Wang

et al. 2017

Oxidative Medicine and Cellular Longevity

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Propofol pretreatment before reperfusion, or propofol conditioning, has been shown to be cardioprotective, while its mechanism is unclear. The current study investigated the roles of endocannabinoid signaling in propofol cardioprotection in an in vivo model of myocardial ischemia/reperfusion (I/R) injury and in in vitro primary cardiomyocyte hypoxia/reoxygenation (H/R) injury. The results showed that propofol conditioning increased both serum and cell culture media concentrations of endocannabinoids including anandamide (AEA) and 2-arachidonoylglycerol (2-AG) detected by LC-MS/MS. The reductions of myocardial infarct size in vivo and cardiomyocyte apoptosis and death in vitro were accompanied with attenuations of oxidative injuries manifested as decreased reactive oxygen species (ROS), malonaldehyde (MDA), and MPO (myeloperoxidase) and increased superoxide dismutase (SOD) production. These effects were mimicked by either URB597, a selective endocannabinoids degradation inhibitor, or VDM11, a selective endocannabinoids reuptake inhibitor. In vivo study further validated that the cardioprotective and antioxidative effects of propofol were reversed by selective CB2 receptor antagonist AM630 but not CB1 receptor antagonist AM251. We concluded that enhancing endogenous endocannabinoid release and subsequent activation of CB2 receptor signaling represent a major mechanism whereby propofol conditioning confers antioxidative and cardioprotective effects against myocardial I/R injury.

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Section: Discussionsupporting

confidence: 79%

Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment‐Induced Cardioprotection against Ischemia‐Reperfusion Injury in Rats

Sun

Lü

Wang

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…The FAAH 385C/A polymorphism converted a conserved proline residue (C allele) to threonine (A allele), which may impact its biochemical and cellular functions (Chiang, ), alter the function or efficiency of catalytic properties and sensitivity to proteolytic degradation, and contribute to susceptibility to several diseases (Chmelikova, Pacal, Spinarova, & Vasku, ; Sipe et al., ; Tyndale et al., ). In vitro and in vivo, the FAAH C/C variant increased FAAH enzyme activity and reduced endocannabinoid levels because of greater degradation of endocannabinoids by FAAH (Doehring, Geisslinger, & Lötsch, ), but the A/A variant reduced cellular activity and expression of the FAAH, which resulted in greatly increase endogenous brain levels of AEA and related fatty acid amides, and participated in addiction and/or reward pathways (Chiang, ; Dincheva et al., ; Sim et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…The FAAH gene genetic variations or polymorphisms that produce a functionally altered enzyme may also be expected to induce dysregulation of the endogenous cannabinoid system and shift tonic levels of these CNS signaling lipids, and resulted in alternation in brain addiction and/or reward pathways (Dincheva et al., ; Sim, Hatim, Reynolds, & Mohamed, ). The FAAH polymorphisms association with multiple diseases (e.g., neoplasms, affective disorders, obesity, and inflammatory bowel disease) were widely studied, especially rs324420 polymorphism (385C/A, P129T) in exon 3 (Chiang, ; Chmelikova, Pacal, Spinarova, & Vasku, ; Flanagan, Gerber, Cadet, Beutler, & Sipe, ; Monteleone, Milano, Petrella, Canestrelli, & Maj, ; Sipe, Chiang, Gerber, Beutler, & Cravatt, ; Storr et al., ; Tyndale et al., ; Vazquez‐Roque et al., ). Individuals of European ancestry who carried the A genotypes (AC and AA) of the 385C/A polymorphism were descent −38% expression of FAAH protein (Abecasis et al., ).…”

Section: Introductionmentioning

confidence: 99%

FAAH levels and its genetic polymorphism association with susceptibility to methamphetamine dependence

Zhang

Liu

Deng

et al. 2019

Annals of Human Genetics

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The fatty acid amide hydrolase (FAAH) gene was involved in the modulation of reward and addiction pathophysiology of illicit drugs abuse, and its polymorphisms might be associated with risk of methamphetamine (METH) dependence. This study aimed to investigate the FAAH mRNA levels in peripheral blood mononuclear cells and plasma protein levels and to analyze the 385C/A polymorphism (rs324420) between METH‐dependent patients and controls. The levels of FAAH mRNA in METH dependence were significantly lower than in controls (P < 0.001), however, its plasma protein underwent a significant ∼2‐fold increase (P < 0.001). The A allele of the 385C/A polymorphism significantly increased the METH dependence risk (P < 0.001, odds ratio [OR] = 1.646, 95% confidence interval [CI] = 1.332–2.034). The carried A genotypes (AA, AC, and AA/AC) of 385C/A polymorphism also increased METH‐dependence risks under a different genetic model (AA vs. CC: P = 0.017, OR = 2.454, 95%CI = 1.171–2.143; AC vs. CC: P < 0.001, OR = 1.818, 95%CI = 1.404–2.353; AC/AA vs. CC: P < 0.001, OR = 1.858, 95%CI = 1.444–2.319). The similar results were obtained after adjusting for age and sex. Unfortunately, we failed to find that any genotype of 385C/A polymorphism affected the mRNA or plasma protein levels in controls, respectively (P > 0.05). These data indicate that the FAAH may play an important role in the pathophysiological process of METH dependence, and the 385C/A polymorphism may be associated with METH dependence susceptibility in a Chinese Han population.

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“…109 In individuals with a personal history of chronic heart failure, it is also reported that AC and AA genotypes of FAAH C385A were associated with an increased risk of MI. 108…”

Section: (Faah) C385a Polymorphism and Obesitymentioning

confidence: 99%

Fatty acid amide hydrolase C385A polymorphism affects susceptibility to various diseases

Anvar

Ahmadalipour

2022

BioFactors

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The endocannabinoid (eCB) system is an important neuromodulatory system with its extensive network of receptors throughout the human body that has complex actions in the nervous system, immune system, and all of the body's other organs. Fatty acid amide hydrolase (FAAH) is an important membranebound homodimeric degrading enzyme that controls the biological activity of N-arachidonoylethanolamide (AEA) in the eCB system and other relevant bioactive lipids. It has been shown that several single nucleotide polymorphisms (SNPs) of FAAH are associated with various phenotypes and diseases including cardiovascular, endocrine, drug abuse, and neuropsychiatric disorders. A common functional and most studied polymorphism of this gene is C385A (rs324420), which results in the replacement of a conserved proline to threonine in the FAAH enzyme structure, leads to a reduction of the activity and expression of FAAH, compromises the inactivation of AEA and causes higher synaptic concentrations of AEA that can be associated with several various phenotypes. The focus of this review is on evidence-based studies on the associations of the FAAH C385A polymorphism and the various diseases or traits.Although there was variability in the results of these reports, the overall consensus is that the FAAH C385A genotype can affect susceptibility to some multifactorial disorders and can be considered a potential therapeutic target.

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Association of polymorphisms in the endocannabinoid system genes with myocardial infarction and plasma cholesterol levels

Cited by 6 publications

References 27 publications

Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment‐Induced Cardioprotection against Ischemia‐Reperfusion Injury in Rats

Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment‐Induced Cardioprotection against Ischemia‐Reperfusion Injury in Rats

FAAH levels and its genetic polymorphism association with susceptibility to methamphetamine dependence

Fatty acid amide hydrolase C385A polymorphism affects susceptibility to various diseases

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