Tissue-specific epigenetics of atherosclerosis-related <i>ANGPT</i> and <i>ANGPTL</i> genes

Ehrlich, Kenneth C.; Lacey, Michelle; Ehrlich, Melanie

doi:10.2217/epi-2018-0150

Cited by 32 publications

(12 citation statements)

References 79 publications

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“…Two REGs ( PLCB1 and ATP1A4 ) that are reportedly involved in hypertension or related organ damage participate in more than one of the mentioned pathways ( 28 , 29 ), in accordance with expectations of co-adaptation of the blood vessel–heart–kidney axis in giraffe. In addition to genes in the mentioned pathways, we also detected other PSGs and REGs that may help to avoid hypertensive damage, including ANGPTL1 , which is associated with the integrity of vascular endothelium ( 30 ), and TGFB1 , which is strongly implicated in multiorgan fibrosis associated with hypertension ( 31 ). The finding of multiple genes involved in several phenotypic traits that share evolutionary constraints due to the extreme stature of the giraffe suggests that pleiotropy may play an important role in evolving such an extreme body plan.…”

Section: Resultsmentioning

confidence: 99%

A towering genome: Experimentally validated adaptations to high blood pressure and extreme stature in the giraffe

et al. 2021

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The suite of adaptations associated with the extreme stature of the giraffe has long interested biologists and physiologists. By generating a high-quality chromosome-level giraffe genome and a comprehensive comparison with other ruminant genomes, we identified a robust catalog of giraffe-specific mutations. These are primarily related to cardiovascular, bone growth, vision, hearing, and circadian functions. Among them, the giraffe FGFRL1 gene is an outlier with seven unique amino acid substitutions not found in any other ruminant. Gene-edited mice with the giraffe-type FGFRL1 show exceptional hypertension resistance and higher bone mineral density, both of which are tightly connected with giraffe adaptations to high stature. Our results facilitate a deeper understanding of the molecular mechanism underpinning distinct giraffe traits, and may provide insights into the study of hypertension in humans.

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Section: Resultsmentioning

confidence: 99%

A towering genome: Experimentally validated adaptations to high blood pressure and extreme stature in the giraffe

et al. 2021

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“…Analysis of human atherosclerotic plaques has demonstrated global DNA hypermethylation, which suggests a strong link between DNA methylation and atherosclerosis development [62]. A recent study analyzing whole-genome epigenetic factors implicated in atherogenesis identified tissue-specific enhancer chromatin regions that probably regulate the transcription of angiopoietin/angiopoietin-like genes that play a crucial role in atherosclerosis and angiogenesis [63]. This sparked the development of new epigenetic drugs targeting chromatin architecture to halt atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Does low-density lipoprotein cholesterol induce inflammation? If so, does it matter? Current insights and future perspectives for novel therapies

Jukema

Ahmed

Tardif

2019

BMC Med

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BackgroundDyslipidemia and inflammation are closely interrelated contributors in the pathogenesis of atherosclerosis. Disorders of lipid metabolism initiate an inflammatory and immune-mediated response in atherosclerosis, while low-density lipoprotein cholesterol (LDL-C) lowering has possible pleiotropic anti-inflammatory effects that extend beyond lipid lowering.Main textActivation of the immune system/inflammasome destabilizes the plaque, which makes it vulnerable to rupture, resulting in major adverse cardiac events (MACE). The activated immune system potentially accelerates atherosclerosis, and atherosclerosis activates the immune system, creating a vicious circle. LDL-C enhances inflammation, which can be measured through multiple parameters like high-sensitivity C-reactive protein (hsCRP). However, multiple studies have shown that CRP is a marker of residual risk and not, itself, a causal factor. Recently, anti-inflammatory therapy has been shown to decelerate atherosclerosis, resulting in fewer MACE. Nevertheless, an important side effect of anti-inflammatory therapy is the potential for increased infection risk, stressing the importance of only targeting patients with high residual inflammatory risk. Multiple (auto-)inflammatory diseases are potentially related to/influenced by LDL-C through inflammasome activation.ConclusionsResearch suggests that LDL-C induces inflammation; inflammation is of proven importance in atherosclerotic disease progression; anti-inflammatory therapies yield promise in lowering (cardiovascular) disease risk, especially in selected patients with high (remaining) inflammatory risk; and intriguing new anti-inflammatory developments, for example, in nucleotide-binding leucine-rich repeat-containing pyrine receptor inflammasome targeting, are currently underway, including novel pathway interventions such as immune cell targeting and epigenetic interference. Long-term safety should be carefully monitored for these new strategies and cost-effectiveness carefully evaluated.

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“…miRNA Regulation by DNA Methylation in AS miRNA-145 miR-145 is an AS-associated miRNA, whereas miR-145encoding sequences contain a DMR in the enhancer chromatin regions thought as an AS-associated DNA hypermethylated DMR (Ehrlich et al, 2019), which may explain why miR-145 plays a different role in cardiovascular diseases (CADs) ( Table 2).…”

Section: Figmentioning

confidence: 99%

Interaction Between microRNA and DNA Methylation in Atherosclerosis

Tao

Xia

Cai

et al. 2021

DNA and Cell Biology

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Atherosclerosis (AS) is a chronic inflammatory disease accompanied by complex pathological changes, such as endothelial dysfunction, foam cell formation, and vascular smooth muscle cell proliferation. Many approaches, including regulating AS-related gene expression in the transcriptional or post-transcriptional level, contribute to alleviating AS development. The DNA methylation is a crucial epigenetic modification in regulating cell function by silencing the relative gene expression. The microRNA (miRNA) is a type of noncoding RNA that plays an important role in gene post-transcriptional regulation and disease development. The DNA methylation and the miRNA are important epigenetic factors in AS. However, recent studies have found a mutual regulation between these two factors in AS development. In this study, recent insights into the roles of miRNA and DNA methylation and their interaction in the AS progression are reviewed.

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Tissue-specific epigenetics of atherosclerosis-related ANGPT and ANGPTL genes

Cited by 32 publications

References 79 publications

A towering genome: Experimentally validated adaptations to high blood pressure and extreme stature in the giraffe

A towering genome: Experimentally validated adaptations to high blood pressure and extreme stature in the giraffe

Does low-density lipoprotein cholesterol induce inflammation? If so, does it matter? Current insights and future perspectives for novel therapies

Interaction Between microRNA and DNA Methylation in Atherosclerosis

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