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Genetic associations and regulation of expression indicate an independent role for 14q32 snoRNAs in Human Cardiovascular Disease

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Harvard

Håkansson, KEJ, Goossens, EAC, Trompet, S, van Ingen, E, de Vries, MR, van der Kwast, RVCT, Ripa, RS, Kastrup, J, Hohensinner, PJ, Kaun, C, Wojta, J, Böhringer, S, le Cessie, S, Jukema, JW, Quax, PHA & Nossent, AY 2019, 'Genetic associations and regulation of expression indicate an independent role for 14q32 snoRNAs in Human Cardiovascular Disease' Cardiovascular Research, bind 115, nr. 10, s. 1519-1532. https://doi.org/10.1093/cvr/cvy309

APA

Håkansson, K. E. J., Goossens, E. A. C., Trompet, S., van Ingen, E., de Vries, M. R., van der Kwast, R. V. C. T., ... Nossent, A. Y. (2019). Genetic associations and regulation of expression indicate an independent role for 14q32 snoRNAs in Human Cardiovascular Disease. Cardiovascular Research, 115(10), 1519-1532. https://doi.org/10.1093/cvr/cvy309

CBE

Håkansson KEJ, Goossens EAC, Trompet S, van Ingen E, de Vries MR, van der Kwast RVCT, Ripa RS, Kastrup J, Hohensinner PJ, Kaun C, Wojta J, Böhringer S, le Cessie S, Jukema JW, Quax PHA, Nossent AY. 2019. Genetic associations and regulation of expression indicate an independent role for 14q32 snoRNAs in Human Cardiovascular Disease. Cardiovascular Research. 115(10):1519-1532. https://doi.org/10.1093/cvr/cvy309

MLA

Vancouver

Håkansson KEJ, Goossens EAC, Trompet S, van Ingen E, de Vries MR, van der Kwast RVCT o.a. Genetic associations and regulation of expression indicate an independent role for 14q32 snoRNAs in Human Cardiovascular Disease. Cardiovascular Research. 2019 jan 1;115(10):1519-1532. https://doi.org/10.1093/cvr/cvy309

Author

Håkansson, Kjell E J ; Goossens, Eveline A C ; Trompet, Stella ; van Ingen, Eva ; de Vries, Margreet R ; van der Kwast, Reginald V C T ; Ripa, Rasmus S ; Kastrup, Jens ; Hohensinner, Philipp J ; Kaun, Christoph ; Wojta, Johann ; Böhringer, Stefan ; le Cessie, Saskia ; Jukema, J Wouter ; Quax, Paul H A ; Nossent, A Yaël. / Genetic associations and regulation of expression indicate an independent role for 14q32 snoRNAs in Human Cardiovascular Disease. I: Cardiovascular Research. 2019 ; Bind 115, Nr. 10. s. 1519-1532.

Bibtex

@article{d90d8422f6ae41069425b83578deb3f0,
title = "Genetic associations and regulation of expression indicate an independent role for 14q32 snoRNAs in Human Cardiovascular Disease",
abstract = "AIMS: We have shown that 14q32 microRNAs are highly involved in vascular remodelling and cardiovascular disease. However, the 14q32 locus also encodes 41 'orphan' small nucleolar RNAs (snoRNAs). We aimed to gather evidence for an independent role for 14q32 snoRNAs in human cardiovascular disease.METHODS AND RESULTS: We performed a lookup of the 14q32 region within the dataset of a genome wide association scan in 5244 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Single nucleotide polymorphisms (SNPs) in the snoRNA-cluster were significantly associated with heart failure. These snoRNA-cluster SNPs were not linked to SNPs in the microRNA-cluster or in MEG3, indicating that snoRNAs modify the risk of cardiovascular disease independently. We looked at expression of 14q32 snoRNAs throughout the human cardio-vasculature. Expression profiles of the 14q32 snoRNAs appeared highly vessel specific. When we compared expression levels of 14q32 snoRNAs in human vena saphena magna (VSM) with those in failed VSM-coronary bypasses, we found that 14q32 snoRNAs were up-regulated. SNORD113.2, which showed a 17-fold up-regulation in failed bypasses, was also up-regulated two-fold in plasma samples drawn from patients with ST-elevation myocardial infarction directly after hospitalization compared with 30 days after start of treatment. However, fitting with the genomic associations, 14q32 snoRNA expression was highest in failing human hearts. In vitro studies show that the 14q32 snoRNAs bind predominantly to methyl-transferase Fibrillarin, indicating that they act through canonical mechanisms, but on non-canonical RNA targets. The canonical C/D-box snoRNA seed sequences were highly conserved between humans and mice.CONCLUSION: 14q32 snoRNAs appear to play an independent role in cardiovascular pathology. 14q32 snoRNAs are specifically regulated throughout the human vasculature and their expression is up-regulated during cardiovascular disease. Our data demonstrate that snoRNAs merit increased effort and attention in future basic and clinical cardiovascular research.",
keywords = "14q32 locus, Cardiovascular disease, DLK1-DIO3, Non-coding RNA, snoRNA, STEMI, Vascular tissue, Vessels",
author = "H{\aa}kansson, {Kjell E J} and Goossens, {Eveline A C} and Stella Trompet and {van Ingen}, Eva and {de Vries}, {Margreet R} and {van der Kwast}, {Reginald V C T} and Ripa, {Rasmus S} and Jens Kastrup and Hohensinner, {Philipp J} and Christoph Kaun and Johann Wojta and Stefan B{\"o}hringer and {le Cessie}, Saskia and Jukema, {J Wouter} and Quax, {Paul H A} and Nossent, {A Ya{\"e}l}",
note = "Published on behalf of the European Society of Cardiology. All rights reserved. {\circledC} The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.",
year = "2019",
month = "1",
day = "1",
doi = "10.1093/cvr/cvy309",
language = "English",
volume = "115",
pages = "1519--1532",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "10",

}

RIS

TY - JOUR

T1 - Genetic associations and regulation of expression indicate an independent role for 14q32 snoRNAs in Human Cardiovascular Disease

AU - Håkansson, Kjell E J

AU - Goossens, Eveline A C

AU - Trompet, Stella

AU - van Ingen, Eva

AU - de Vries, Margreet R

AU - van der Kwast, Reginald V C T

AU - Ripa, Rasmus S

AU - Kastrup, Jens

AU - Hohensinner, Philipp J

AU - Kaun, Christoph

AU - Wojta, Johann

AU - Böhringer, Stefan

AU - le Cessie, Saskia

AU - Jukema, J Wouter

AU - Quax, Paul H A

AU - Nossent, A Yaël

N1 - Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - AIMS: We have shown that 14q32 microRNAs are highly involved in vascular remodelling and cardiovascular disease. However, the 14q32 locus also encodes 41 'orphan' small nucleolar RNAs (snoRNAs). We aimed to gather evidence for an independent role for 14q32 snoRNAs in human cardiovascular disease.METHODS AND RESULTS: We performed a lookup of the 14q32 region within the dataset of a genome wide association scan in 5244 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Single nucleotide polymorphisms (SNPs) in the snoRNA-cluster were significantly associated with heart failure. These snoRNA-cluster SNPs were not linked to SNPs in the microRNA-cluster or in MEG3, indicating that snoRNAs modify the risk of cardiovascular disease independently. We looked at expression of 14q32 snoRNAs throughout the human cardio-vasculature. Expression profiles of the 14q32 snoRNAs appeared highly vessel specific. When we compared expression levels of 14q32 snoRNAs in human vena saphena magna (VSM) with those in failed VSM-coronary bypasses, we found that 14q32 snoRNAs were up-regulated. SNORD113.2, which showed a 17-fold up-regulation in failed bypasses, was also up-regulated two-fold in plasma samples drawn from patients with ST-elevation myocardial infarction directly after hospitalization compared with 30 days after start of treatment. However, fitting with the genomic associations, 14q32 snoRNA expression was highest in failing human hearts. In vitro studies show that the 14q32 snoRNAs bind predominantly to methyl-transferase Fibrillarin, indicating that they act through canonical mechanisms, but on non-canonical RNA targets. The canonical C/D-box snoRNA seed sequences were highly conserved between humans and mice.CONCLUSION: 14q32 snoRNAs appear to play an independent role in cardiovascular pathology. 14q32 snoRNAs are specifically regulated throughout the human vasculature and their expression is up-regulated during cardiovascular disease. Our data demonstrate that snoRNAs merit increased effort and attention in future basic and clinical cardiovascular research.

AB - AIMS: We have shown that 14q32 microRNAs are highly involved in vascular remodelling and cardiovascular disease. However, the 14q32 locus also encodes 41 'orphan' small nucleolar RNAs (snoRNAs). We aimed to gather evidence for an independent role for 14q32 snoRNAs in human cardiovascular disease.METHODS AND RESULTS: We performed a lookup of the 14q32 region within the dataset of a genome wide association scan in 5244 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Single nucleotide polymorphisms (SNPs) in the snoRNA-cluster were significantly associated with heart failure. These snoRNA-cluster SNPs were not linked to SNPs in the microRNA-cluster or in MEG3, indicating that snoRNAs modify the risk of cardiovascular disease independently. We looked at expression of 14q32 snoRNAs throughout the human cardio-vasculature. Expression profiles of the 14q32 snoRNAs appeared highly vessel specific. When we compared expression levels of 14q32 snoRNAs in human vena saphena magna (VSM) with those in failed VSM-coronary bypasses, we found that 14q32 snoRNAs were up-regulated. SNORD113.2, which showed a 17-fold up-regulation in failed bypasses, was also up-regulated two-fold in plasma samples drawn from patients with ST-elevation myocardial infarction directly after hospitalization compared with 30 days after start of treatment. However, fitting with the genomic associations, 14q32 snoRNA expression was highest in failing human hearts. In vitro studies show that the 14q32 snoRNAs bind predominantly to methyl-transferase Fibrillarin, indicating that they act through canonical mechanisms, but on non-canonical RNA targets. The canonical C/D-box snoRNA seed sequences were highly conserved between humans and mice.CONCLUSION: 14q32 snoRNAs appear to play an independent role in cardiovascular pathology. 14q32 snoRNAs are specifically regulated throughout the human vasculature and their expression is up-regulated during cardiovascular disease. Our data demonstrate that snoRNAs merit increased effort and attention in future basic and clinical cardiovascular research.

KW - 14q32 locus

KW - Cardiovascular disease

KW - DLK1-DIO3

KW - Non-coding RNA

KW - snoRNA

KW - STEMI

KW - Vascular tissue

KW - Vessels

U2 - 10.1093/cvr/cvy309

DO - 10.1093/cvr/cvy309

M3 - Journal article

VL - 115

SP - 1519

EP - 1532

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 10

ER -

ID: 56431756