MicroRNA-665 is involved in the regulation of the expression of the cardioprotective cannabinoid receptor CB2 in patients with severe heart failure

Möhnle, Patrick; Schütz, Stefanie V.; Schmidt, Marc T.; Hinske, Christian; Hübner, Max; Heyn, Jens; Beiras-Fernández, Andrés; Kreth, Simone

doi:10.1016/j.bbrc.2014.08.008

Cited by 29 publications

(21 citation statements)

References 32 publications

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“…Upregulation of cannabinoid receptors has been shown in cardiac pathologies, particularly CB 2 , which is upregulated in chronic heart failure (Weis et al 2010), in aortic stenosis (Duerr et al 2013) and in ischaemia/reperfusion (Duerr et al 2014). CB 2 expression is under the control of microRNA-665 (miR-665), whose expression is increased in heart failure (Mohnle et al 2014). The hypothesis that endocannabinoids are protective in cardiac dysfunction comes from multiple pieces of evidence.…”

Section: Cardioprotective Effects Of Endocannabinoidsmentioning

confidence: 99%

Endocannabinoids and the Cardiovascular System in Health and Disease

O’Sullivan

2015

Handbook of Experimental Pharmacology

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The endocannabinoid system is widely distributed throughout the cardiovascular system. Endocannabinoids play a minimal role in the regulation of cardiovascular function in normal conditions, but are altered in most cardiovascular disorders. In shock, endocannabinoids released within blood mediate the associated hypotension through CB(1) activation. In hypertension, there is evidence for changes in the expression of CB(1), and CB(1) antagonism reduces blood pressure in obese hypertensive and diabetic patients. The endocannabinoid system is also upregulated in cardiac pathologies. This is likely to be cardioprotective, via CB(2) and CB(1) (lesser extent). In the vasculature, endocannabinoids cause vasorelaxation through activation of multiple target sites, inhibition of calcium channels, activation of potassium channels, NO production and the release of vasoactive substances. Changes in the expression or function of any of these pathways alter the vascular effect of endocannabinoids. Endocannabinoids have positive (CB(2)) and negative effects (CB(1)) on the progression of atherosclerosis. However, any negative effects of CB(1) may not be consequential, as chronic CB(1) antagonism in large scale human trials was not associated with significant reductions in atheroma. In neurovascular disorders such as stroke, endocannabinoids are upregulated and protective, involving activation of CB(1), CB(2), TRPV1 and PPARα. Although most of this evidence is from preclinical studies, it seems likely that cannabinoid-based therapies could be beneficial in a range of cardiovascular disorders.

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Section: Cardioprotective Effects Of Endocannabinoidsmentioning

confidence: 99%

Endocannabinoids and the Cardiovascular System in Health and Disease

O’Sullivan

2015

Handbook of Experimental Pharmacology

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“…These include the cannabinoid receptor type 1 (CB1R), cannabinoid receptor type 2 (CBR2), vanilloid, prostanoid, lysophospholipid and unidentified endocannabinoid pathways, among others, 6 which interact in complex ways with immune active cells and cytokines, [7][8][9] all of which are subject to increasingly complex levels of epigenetic regulation. 10 Case reports exist of serious adverse effects including supraventricular and ventricular arrhythmias, coronary thrombosis, sudden cardiac death, asystole, angina, epicardial coronary spasm and microvascular mediated no-flow phenomena frequently in very young patients or patients without other cardiovascular risk factors which have been recently collated. 11 12 A threefold to fivefold elevation of all causes and cardiac death has been shown within 1 hour of cannabis use in cross-sectional 13 and longitudinal studies.…”

Section: Introductionmentioning

confidence: 99%

Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study

2016

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ObjectivesMany reports exist of the cardiovascular toxicity of smoked cannabis but none of arterial stiffness measures or vascular age (VA). In view of its diverse toxicology, the possibility that cannabis-exposed patients may be ageing more quickly requires investigation.DesignCross-sectional and longitudinal, observational. Prospective.SettingSingle primary care addiction clinic in Brisbane, Australia.Participants11 cannabis-only smokers, 504 tobacco-only smokers, 114 tobacco and cannabis smokers and 534 non-smokers. Exclusions: known cardiovascular disease or therapy or acute exposure to alcohol, amphetamine, heroin or methadone.InterventionRadial arterial pulse wave tonometry (AtCor, SphygmoCor, Sydney) performed opportunistically and sequentially on patients between 2006 and 2011.Main outcome measureAlgorithmically calculated VA. Secondary outcomes: other central haemodynamic variables.ResultsDifferences between group chronological ages (CA, 30.47±0.48 to 40.36±2.44, mean±SEM) were controlled with linear regression. Between-group sex differences were controlled by single-sex analysis. Mean cannabis exposure among patients was 37.67±7.16 g-years. In regression models controlling for CA, Body Mass Index (BMI), time and inhalant group, the effect of cannabis use on VA was significant in males (p=0.0156) and females (p=0.0084). The effect size in males was 11.84%. A dose–response relationship was demonstrated with lifetime exposure (p<0.002) additional to that of tobacco and opioids. In both sexes, the effect of cannabis was robust to adjustment and was unrelated to its acute effects. Significant power interactions between cannabis exposure and the square and cube of CA were demonstrated (from p<0.002).ConclusionsCannabis is an interactive cardiovascular risk factor (additional to tobacco and opioids), shows a prominent dose–response effect and is robust to adjustment. Cannabis use is associated with an acceleration of the cardiovascular age, which is a powerful surrogate for the organismal–biological age. This likely underlies and bi-directionally interacts with its diverse toxicological profile and is of considerable public health and regulatory importance.

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“…Many studies have proved that there were close relationships between miRNAs and cancers, but the mechanism needed more researches. Some experiments displayed that miRNAs could acts as posttranscriptional regulators to regulate gene expression via binding to 3′-untranslated region (3′-UTR) of their target mRNAs [23,30]. Then, we used prediction software to obtain a potential target of miR-665-NLK.…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNA-665 (miR-665), an exosomal miRNA, has been found that it is associated with different diseases, like congestive heart failure [23], anesthesia-related cognitive dysfunction [24], in ammatory bowel disease [25], and cancer [26]. Interestingly, miR-665 showed different functions for different diseases.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-665 Regulated Cell Proliferation, Migration and Apoptosis by Targeting Nemo-like Kinase in Non-small Cell Lung Cancer

Huang

Yue

et al. 2020

Preprint

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Background: Many evidences proved important roles of microRNAs in the occurrence and development of non-small cell lung cancer (NSCLC). This work aimed to explore the effects and regulating mechanism of microRNA-665 (miR-665) in NSCLC. Methods: Here, quantitative real time PCR was used to evaluate the expression level of miR-665 in NSCLC tissues and several cell lines (H520, H1299, PC9, H358, and A549). Then, MTT, apoptosis assays and wound-healing assays were performed to study miR-665 functions on cell proliferation, apoptosis and migration. Based on bioinformatics analysis, nemo-like kinase (NLK) was predicted as a potential target of miR-665 and then a series of experiments were performed to explore miR-665 mechanism.Results: In NSCLC tissues and several cell lines, miR-665 was up-regulated and cell experiments displayed that it had abilities to promote cell proliferation and migration, and inhibit cell apoptosis. MiR-665 over-expression could reduce NLK mRNA and protein level by binding to 3′-untranslated region of NLK, which suggested that miR-665 could regulate NLK expression. Further analysis found that there was an inverse correlation f between miR-665 and NLK in NSCLC. Moreover, low-level NLK possessed same effects on cells as miR-665 over-expression, and its knockdown could partly recovery the miR-665-mediated cell proliferation, migration and anti-apoptosis, indicating that miR-665 might regulate biological behaviors of NSCLC cells via targeting NLK. Conclusion: MiR-665 probably promoted NSCLC occurrence and progression via targeting NLK, which might be a hopeful biomarker for NSCLC diagnosis or a target for treatment.

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MicroRNA-665 is involved in the regulation of the expression of the cardioprotective cannabinoid receptor CB2 in patients with severe heart failure

Cited by 29 publications

References 32 publications

Endocannabinoids and the Cardiovascular System in Health and Disease

Endocannabinoids and the Cardiovascular System in Health and Disease

Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study

MicroRNA-665 Regulated Cell Proliferation, Migration and Apoptosis by Targeting Nemo-like Kinase in Non-small Cell Lung Cancer

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