Abstract
AbstractAtherosclerosis commonly remains undiagnosed until disease manifestations occur. The disease is associated with dysregulated micro(mi)RNAs, but how this is linked to atherosclerosis-related immune reactions is largely unknown. A mouse model of carotid atherosclerosis, human APOB100-transgenic Ldlr−/− (HuBL), was used to study the spatiotemporal dysregulation of a set of miRNAs. Middle-aged HuBL mice with established atherosclerosis had decreased levels of miR-143-3p in their carotid arteries. In young HuBL mice, early atherosclerosis was observed in the carotid bifurcation, which had lower levels of miR-15a-5p, miR-143-3p, and miR-199a-3p, and higher levels of miR-155-5p. The dysregulation of these miRNAs was reflected by specific immune responses during atheroprogression. Finally, levels of miR-143-3p were 70.6% lower in extracellular vesicles isolated from the plasma of patients with carotid stenosis compared to healthy controls. Since miR-143-3p levels progressively decrease when transitioning between early and late experimental carotid atherosclerosis, we propose it as a biomarker for atherosclerosis.
Graphical Abstract
Low levels of miR-143-3p in plasma extracellular vesicles can serve as a biomarker for atherosclerosis, and dysregulation of microRNAs is linked to the immune reactions associated with disease progression
Funder
Hjärt-Lungfonden
Åke Wiberg Stiftelse
Jeanssons Stiftelser
Gun och Bertil Stohnes Stiftelse
Foundation for Geriatric Diseases at Karolinska Institutet
Karolinska Institutet Research Foundation
Stiftelsen för Gamla Tjänarinnor
Spanish Ministry of Science and Innovation
European Federation of Immunological Societies
Karolinska Institute
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Cardiology and Cardiovascular Medicine,Pharmaceutical Science,Genetics,Molecular Medicine