MicroRNAs and lipoproteins: A connection beyond atherosclerosis?

Norata, Giuseppe Danilo; Sala, Federica; Catapano, Alberico L.; Fernández‐Hernando, Carlos

doi:10.1016/j.atherosclerosis.2012.11.019

Cited by 39 publications

(28 citation statements)

References 60 publications

(67 reference statements)

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“…[31][32][33][34][35] In this Review, we summarise how miRNAs provide a link between endothelial injury and inflammation, and how these molecules can mediate inflammatory activation and lipid accumulation in macrophages during atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-mediated mechanisms of the cellular stress response in atherosclerosis

2015

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| Atherosclerosis is characterised by the accumulation of lipid-laden macrophages in atherosclerotic lesions and occurs preferentially at arterial branching points, which are prone to inflammation during hyperlipidaemic stress. The increased susceptibility at branching sites of arteries is attributable to poor adaptation of arterial endothelial cells to disturbed blood flow. In the past 5 years, several studies have provided mechanistic insights into the regulatory roles of microRNAs (miRNAs) in inflammatory activation, proliferation, and regeneration of endothelial cells during this maladaptive process. The intercellular transfer of vesicle-bound miRNAs contributes to arterial homeostasis, and the combinatorial effect of multiple miRNAs controls the unresolved inflammation orchestrated by macrophages in atherosclerotic lesions. In this Review, we highlight the miRNA-dependent regulation of the endothelial phenotype and the proliferative reserve that occurs in response to altered haemodynamic conditions as a prerequisite for atherogenic inflammation. In particular, we discuss the regulation of transcriptional modules by miRNAs and the protective role of complementary strand pairs, which encompasses remote miRNA signalling. In addition, we review the roles of miRNA tandems and describe the relevance of RNA target selection and competition to the behaviour of lesional macrophages. Elucidating miRNA-mediated regulatory mechanisms can aid the development of novel diagnostic and therapeutic strategies for atherosclerosis. Schober, A. et al. Nat. Rev. Cardiol. advance online publication 7

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“…Importantly, microRNA-144 levels were increased in the plasma of mouse and humans subjected to limb RIC. Plasma carriage of microRNAs, to prevent digestion by circulating RNase, has been demonstrated within lipoprotein complexes in association with specific carrier proteins, such as argonaute, and in exosomes (56–59). Interestingly, the total number of exosomes in mouse plasma after RIC did not increase (60), although others observed increased numbers of exosomes following RIC in both rats and humans (61).…”

Section: Signal Transduction Of Ricmentioning

confidence: 99%

Remote Ischemic Conditioning

Heusch

Bøtker

Przyklenk

et al. 2015

Journal of the American College of Cardiology

510

507

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In remote ischemic conditioning (RIC) brief, reversible episodes of ischemia with reperfusion in one vascular bed, tissue or organ confer a global protective phenotype and render remote tissues and organs resistant to ischemia/reperfusion injury. The peripheral stimulus can be chemical, mechanical or electrical and involves activation of peripheral sensory nerves. The signal transfer to the heart or other organs is through neuronal and humoral communications. Protection can be transferred, even across species, with plasma-derived dialysate and involves nitric oxide, stromal derived factor-1α, microRNA-144, but also other, not yet identified factors. Intracardiac signal transduction involves: adenosine, bradykinin, cytokines, and chemokines, which activate specific receptors; intracellular kinases; and mitochondrial function. RIC by repeated brief inflation/deflation of a blood pressure cuff protects against endothelial dysfunction and myocardial injury in percutaneous coronary interventions, coronary artery bypass grafting and reperfused acute myocardial infarction. RIC is safe and effective, noninvasive, easily feasible and inexpensive.

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“…1) (for review see Jung and Suh, 2012). The mature miRNA strand is incorporated into an Argonaute-containing RNA-induced silencing complex (RISC) (Norata et al, 2013). The RISC can bind to 3′UTR of target mRNA and mediate deadenylation and degradation of mRNA.…”

Section: Introductionmentioning

confidence: 99%

Circulating miRNAs in Ageing and Ageing-Related Diseases

Jung

Suh

2014

Journal of Genetics and Genomics

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MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They are involved in important biological processes including development, homeostasis, and ageing. Recently, extracellular miRNAs have been discovered in the bloodstream and bodily fluids. These miRNAs are shown to be secreted and circulating in microvesicles (MVs), or in complex with other factors such as RNA-binding proteins and high-density lipoprotein (HDL) particles. These cell-free, circulating miRNAs can be taken into and function as negative regulators of target genes in recipient cells. Here we review the biogenesis and uptake of circulating miRNAs as well as their profiles in ageing and ageing-related diseases. We discuss the emerging role of circulating miRNAs as biomarkers and therapeutic targets.

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“…In a mouse model of brain endothelial cells in systemic lupus erythematosus, C5a seems to regulate miRNA expression [116]. MiRNAs are attractive targets for therapeutic intervention, and currently several research projects address miRNAs, also in lipoproteins and atherosclerosis [117]. Since there seems to be a connection between innate immunity and miRNAs, this connection should also be further explored in the field of atherosclerosis.…”

Section: Crosstalk Between Complement the Tlrs And Other Systems Relmentioning

confidence: 98%

The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis

et al. 2015

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Despite recent medical advances, atherosclerosis is a global burden accounting for numerous deaths and hospital admissions. Immune-mediated inflammation is a major component of the atherosclerotic process, but earlier research focus on adaptive immunity has gradually switched towards the role of innate immunity. The complement system and toll-like receptors (TLRs), and the crosstalk between them, may be of particular interest both with respect to pathogenesis and as therapeutic targets in atherosclerosis. Animal studies indicate that inhibition of C3a and C5a reduces atherosclerosis. In humans modified LDL-cholesterol activate complement and TLRs leading to downstream inflammation, and histopathological studies indicate that the innate immune system is present in atherosclerotic lesions. Moreover, clinical studies have demonstrated that both complement and TLRs are upregulated in atherosclerotic diseases, although interventional trials have this far been disappointing. However, based on recent research showing an intimate interplay between complement and TLRs we propose a model in which combined inhibition of both complement and TLRs may represent a potent anti-inflammatory therapeutic approach to reduce atherosclerosis.

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“…ASOs can also be made to novel regulatory mechanisms that cannot be targeted with conventional therapies such as miRNA-27b, miRNA-122, and miRNA-33 which are involved in the control of lipid metabolism [64][65][66]. Production of the cellular cholesterol transporter ABC-A1 and ABC-G1 is inhibited by miRNA 33a and 33b which are located within the intron of sterol regulatory element-binding proteins (SREBP) 2 and SREBP1, respectively.…”

Section: Other Targets For Asosmentioning

confidence: 99%