9.2 DELETION OF CHROMOSOME 9P21 NONCODING CARDIOVASCULAR RISK INTERVAL IN MICE INDUCES A PROTHROMBOTIC PHENOTYPE

DOI

10.1016/j.artres.2016.10.069How to use a DOI?

Abstract

Background: SNPs on chromosome 9p21.3 risk locus have been associated with cardiovascular diseases. We have established a direct mechanistic link between 9p21 noncoding risk interval and susceptibility to aneurysm in a mouse model with a targeted deletion of the 9p21 noncoding cardiovascular disease risk interval.

The deficiency of transcripts encoded by this locus predisposes to a pro-thrombotic phenotype and arterial stiffening in this mouse model and in humans with 9p21 DNA variants.

Methods: Carotid blood flow following FeCl3 application was monitored via Doppler profiles. Results: The deletion of the orthologous 70-kb noncoding interval on mouse chromosome 4 (chr4Δ70kb/Δ70kb), synthetic to human chromosome 9p21, predisposes to arterial thrombosis. The time to occlusion in a FeCl3-induced carotid thrombosis model was significantly decreased by 30% in the absence of the locus and confirmed by a new model of physiological thrombosis. There was no difference between groups in blood pressure, carotid stiffness parameters (diameter and distensibility for a given level of arterial pressure) or in vascular structure. We explored the potential impact of the deletion locus on thrombin generation as well as on platelet aggregation and reactivity all were increased compared to controls. In 100 healthy carriers of the 9p21 risk T allele display an increased aortic arterial stiffness compared with carriers of the C allele.

Conclusion: These results establish a direct link between variants or deletion in the 9p21 non-coding risk interval and increased platelet reactivity and thrombin generation predisposing to thrombosis in mouse and increased arterial stiffness in aged population.

Open Access

This is an open access article distributed under the CC BY-NC license.

TY  - JOUR
AU  - Amel Mohamadi
AU  - Mustapha Bourhim
AU  - Gemma Basatemur
AU  - Huguette Louis
AU  - Athanase Benetos
AU  - Patrick Lacolley
AU  - Ziad Mallat
AU  - Veronique Regnault
PY  - 2016
DA  - 2016/11/24
TI  - 9.2 DELETION OF CHROMOSOME 9P21 NONCODING CARDIOVASCULAR RISK INTERVAL IN MICE INDUCES A PROTHROMBOTIC PHENOTYPE
JO  - Artery Research
SP  - 68
EP  - 68
VL  - 16
IS  - C
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2016.10.069
DO  - 10.1016/j.artres.2016.10.069
ID  - Mohamadi2016
ER  -