From genotype to phenotype in human atherosclerosis - recent findings

Holdt, Lesca M.; Teupser, Daniel

doi:10.1097/mol.0b013e3283654e7c

Cited by 54 publications

(52 citation statements)

References 91 publications

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“…From a molecular perspective, ANRIL like several other lncRNAs, recruits Polycomb repressive complexes 1 and 2 and Polycomb-associated activating proteins RYBP and YY1, influencing gene expression both in cis and in trans [141]. …”

Section: Noncoding Rna In Cardiovascular Aging and Age-associated mentioning

confidence: 99%

Noncoding RNA in age-related cardiovascular diseases

Greco

Gorospe

Martelli

2015

Journal of Molecular and Cellular Cardiology

101

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Eukaryotic gene expression is tightly regulated transcriptionally and post-transcriptionally by a host of noncoding (nc)RNAs. The best-studied class of short ncRNAs, microRNAs, mainly repress gene expression post-transcriptionally. Long noncoding (lnc)RNAs, which comprise RNAs differing widely in length and function, can regulate gene transcription as well as post-transcriptional mRNA fate. Collectively, ncRNAs affect a broad range of age-related physiologic deteriorations and pathologies, including reduced cardiovascular vigor and age-associated cardiovascular disease. This review presents an update of our understanding of regulatory ncRNAs contributing to cardiovascular health and disease as a function of advancing age. We will discuss (1) regulatory ncRNAs that control aging-associated cardiovascular homeostasis and disease, (2) the concepts, approaches, and methodologies needed to study regulatory ncRNAs in cardiovascular aging and (3) the challenges and opportunities that age-associated regulatory ncRNAs present in cardiovascular physiology and pathology. This article is part of a Special Issue entitled “CV Aging”.

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Section: Noncoding Rna In Cardiovascular Aging and Age-associated mentioning

confidence: 99%

Noncoding RNA in age-related cardiovascular diseases

Greco

Gorospe

Martelli

2015

Journal of Molecular and Cellular Cardiology

101

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“…Genome-wide association studies (GWAS) are an effective strategy for investigating complex diseases, such as atherosclerosis, and have led to the identification of a substantial number of novel susceptible genetic loci associated with various diseases and traits2021. These findings have served as valuable resources for uncovering the causal genes and underlying molecular mechanisms that drive corresponding phenotypes22.…”

mentioning

confidence: 99%

“…The recent studies evaluating the role of FTO in obesity23 and the role of BCL11A in the regulation of globin switching24 are representative of the significant developments that have resulted from GWAS follow-up studies. Many loci associated with atherosclerosis and atherosclerosis-related complications have been identified, such as 9p21, and the majority of these represent novel markers21. However, few studies combined GWAS result to investigate the long noncoding RNA function in atherosclerosis development.…”

mentioning

confidence: 99%

Long noncoding RNA LINC00305 promotes inflammation by activating the AHRR-NF-κB pathway in human monocytes

Zhang

Wang

Xiong

et al. 2017

Sci Rep

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Accumulating data from genome-wide association studies (GWAS) have provided a collection of novel candidate genes associated with complex diseases, such as atherosclerosis. We identified an atherosclerosis-associated single-nucleotide polymorphism (SNP) located in the intron of the long noncoding RNA (lncRNA) LINC00305 by searching the GWAS database. Although the function of LINC00305 is unknown, we found that LINC00305 expression is enriched in atherosclerotic plaques and monocytes. Overexpression of LINC00305 promoted the expression of inflammation-associated genes in THP-1 cells and reduced the expression of contractile markers in co-cultured human aortic smooth muscle cells (HASMCs). We showed that overexpression of LINC00305 activated nuclear factor-kappa beta (NF-κB) and that inhibition of NF-κB abolished LINC00305-mediated activation of cytokine expression. Mechanistically, LINC00305 interacted with lipocalin-1 interacting membrane receptor (LIMR), enhanced the interaction of LIMR and aryl-hydrocarbon receptor repressor (AHRR), and promoted protein expression as well as nuclear localization of AHRR. Moreover, LINC00305 activated NF-κB exclusively in the presence of LIMR and AHRR. In light of these findings, we propose that LINC00305 promotes monocyte inflammation by facilitating LIMR and AHRR cooperation and the AHRR activation, which eventually activates NF-κB, thereby inducing HASMC phenotype switching.

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“…The rs2026458 identified in this study with remarkable influence on artery calcification is located in Chr6p24 within the gene PHACTR1, one of the established genetic markers for cardiovascular disease [21]. PHACTR1 is an inhibitor of protein phosphatase 1 (PP1), a prevalent enzyme regulating essential cellular processes including cell cycle progression, protein synthesis, carbohydrate metabolism and neuronal signaling through dephosphorylation of different substrates [24].…”

Section: Discussionmentioning

confidence: 98%