Endonuclease V Regulates Atherosclerosis Through C-C Motif Chemokine Ligand 2-Mediated Monocyte Infiltration.

Abstract

Background In cardiovascular diseases, atherosclerotic disorder are the most frequent and important with respect to morbidity and mortality. Inflammation mediated by immune cells is central in all parts of the atherosclerotic progress, and further understanding of the underlying mechanisms is needed. Growing evidence suggests that deamination of adenosine-to-inosine in RNA is crucial for a correct immune response; nevertheless, the role of adenosine-to-inosine RNA editing in atherogenesis has barely been studied. Several proteins have affinity for inosines in RNA, one being ENDOV (endonuclease V), which binds and cleaves RNA at inosines. Data on ENDOV in atherosclerosis are lacking. Methods and Results Quantitative polymerase chain reaction on ENDOV mRNA showed an increased level in human carotid atherosclerotic plaques compared with control veins. Inosine-ribonuclease activity as measured by an enzyme activity assay is detected in immune cells relevant for the atherosclerotic process. Abolishing EndoV in atherogenic apolipoprotein E-deficient (ApoE-/-) mice reduces the atherosclerotic plaque burden, both in size and lipid content. In addition, in a brain stroke model, mice without ENDOV suffer less damage than control mice. Finally, lack of EndoV reduces the recruitment of monocytes to atherosclerotic lesions in atherogenic ApoE-/- mice. Conclusions ENDOV is upregulated in human atherosclerotic lesions, and data from mice suggest that ENDOV promotes atherogenesis by enhancing the monocyte recruitment into the atherosclerotic lesion, potentially by increasing the effect of CCL2 activation on these cells.

• Authors: Xiang Yi Kong, Camilla Huse, Kuan Yang, Jonas Øgaard, Natalia Berges, Erik Sebastian Vik, Meh Sameen Nawaz, Ana Quiles-Jiménez, Azhar Abbas, Ida Gregersen, Sverre Holm, Vigdis Bjerkli, Azita Rashidi, Cathrine Fladeby, Rajikala Suganthan, Ellen Lund Sagen, Mona Skjelland, Anna Lång, Stig Ove Bøe, Magnar Bjørås, Pål Aukrust, Ingrun Alseth, Bente Halvorsen, Tuva Børresdatter Dahl
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 10 Issue 14 Pg. e020656 (07 20 2021) ISSN: 2047-9980 [Electronic] England
• PMID: 34259011 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ccl2 protein, mouse
• Chemokine CCL2
• Cytokines
• RNA
• Deoxyribonuclease (Pyrimidine Dimer)

Topics

• Aged
• Animals
• Aorta, Thoracic (metabolism, pathology)
• Atherosclerosis (genetics, metabolism, pathology)
• Chemokine CCL2 (biosynthesis, genetics)
• Cytokines
• Deoxyribonuclease (Pyrimidine Dimer) (biosynthesis, genetics)
• Disease Models, Animal
• Disease Progression
• Female
• Follow-Up Studies
• Gene Expression Regulation
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Monocytes (metabolism, pathology)
• RNA (genetics)
• Retrospective Studies