| Title: |
Abstract 4131674: ADP-Ribosylation In a Mouse Model of Atherosclerosis: a Potential Novel Link Between Dyslipidemia and Inflammation in Cardiovascular Disease |
| Authors: |
Delwarde, Constance; Pestana, Diego; Kasai, Taku; Kuraoka, Shiori; Nakamura, Yuto; Okada, Takeshi; Decano, Julius; Chelvanambi, Sarvesh; Ge, Rile; Mlynarchik, Andrew; Perez, katelyn; Campedelli, Alesandra; Sonawane, Abhijeet; Aikawa, Elena; Singh, Sasha; Aikawa, Masanori |
| Source: |
Circulation ; volume 150, issue Suppl_1 ; ISSN 0009-7322 1524-4539 |
| Publisher Information: |
Ovid Technologies (Wolters Kluwer Health) |
| Publication Year: |
2024 |
| Description: |
Background: Inflammation and lipid accumulation are major features of atherosclerosis, a leading cause of death and morbidity worldwide. Our previous study recognized ADP-ribosylation, a post-translational modification, as a novel regulator of macrophage activation. We also have established mass spectrometry-based ADP-ribosylation proteomics. Using this technology, we evaluated the completely uncharacterized role of ADP-ribosylation in atherogenesis. We hypothesized that ADP-ribosylated proteins circulate from liver, accumulate in aorta and promote atherogenesis. Methods and Results: We harvested the aorta, liver, and plasma of LDL receptor-deficient ( Ldlr -/- ) mice that were on a regular chow or high-fat diet for 3 or 6 months (n=40/condition). To increase ADP-ribosyl peptide signals in the aorta, we applied our novel recently optimized ion mobility mass spectrometry strategy to generate ADP-ribosylation proteomics data. We analyzed 160 mice aortas and identified 3 APOA1 and 3 APOE ADP-ribosylated peptides in both the aorta and the liver (Fig. A). In addition, these peptides were differentially abundant in the aorta of HFD-fed mice, compared to controls (i.e, APOA1 ARPALEDLR peptide relative abundance (Fig. B)). Using the same mouse plasma, we then validated the presence of ADP-ribosylated APOA1 and ADP-ribosylated APOE in HDL and chylomicron/VLDL/LDL fractions (Western blot), respectively. This finding indicates that classical apolipoproteins circulate as ADP-ribosylated forms, representing a completely novel class of modified apolipoproteins. Immunohistochemistry confirmed the enrichment of aortic lesions in macrophages and ADP-ribosylation signal (5-fold increase, p=0.0006). Conclusions: This work provides the first in vivo evidence that ADP-ribosylation occurs in atherosclerotic lesions, which may originate from the liver via circulating blood (Fig. C). Future studies will examine whether ADP-ribosylation of apolipoproteins, specifically APOA1, alters anti-atherogenic functions of HDL. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1161/circ.150.suppl_1.4131674 |
| Availability: |
https://doi.org/10.1161/circ.150.suppl_1.4131674; https://journals.lww.com/10.1161/circ.150.suppl_1.4131674 |
| Accession Number: |
edsbas.AA7DC677 |
| Database: |
BASE |