DHA and EPA alleviate atherosclerosis by synergistically regulating the aorta–liver axis via miRNA networks
5 affiliations
- 1Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Department of Cardiology, The First Affiliated Hospital of Ningbo University
- 2Laboratory of Food Nutrition and Clinical Research, Institute of Seafood, Zhejiang Gongshang University
- 3Department of Cardiology, Central Laboratory of Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital
- 4Department of Cardiology, Jinhua Central Hospital
- 5Heart Center, Department of Cardiovascular Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College
Abstract
The anti-atherosclerotic effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are well-documented, yet the underlying molecular mechanisms, particularly via cross-organ crosstalk, remain unclear. Here, a high-fat diet-induced atherosclerosis (AS) model in ApoE –/– mice was constructed. Compared with controls, AS mice exhibited elevated serum total cholesterol, triglyceride and low-density lipoprotein cholesterol levels, along with reduced high-density lipoprotein cholesterol levels, impaired hepatic and cardiac function, enlarged aortic plaque area, and pronounced hepatic steatosis and cardiac lipid deposition. DHA/EPA intervention reversed these biochemical and histopathological abnormalities, and conferred superior hepatoprotection than Atorvastatin. Transcriptomics identified 1453 and 1663 differentially expressed genes in liver and aorta of AS mice, respectively. DHA/EPA up-regulated genes related to hepatic cholesterol metabolism and bile acid synthesis, and aortic genes encoding ABC transporters and PPAR signaling components. Conversely, they suppressed hepatic IL-17 signaling and endothelial adhesion molecules. MicroRNA quantification showed significant modulation of aortic miR-33a, miR-146a-3p, miR-155 and miR-223-3p levels, implicating regulation of lipid metabolism and inflammation. Collectively, these data indicate that DHA and EPA exert synergistic anti-atherosclerotic effects via the aorta-liver axis, regulating lipid metabolism, inflammation and vascular remodeling via a miR-30a/146a-3p/223-3p mediated network. These findings provide experimental and mechanistic supports for nutritional intervention of AS.
Related
- Pancreatic α cells are required for nutrient homeostasis by regulating dynamic β cell networks in islets
- MTA1 promotes hepatocellular carcinoma progression by remodeling the immune microenvironment and regulating drug resistance gene networks: an integrated multi-database analysis.
- Planned Impella 5.5 Support via Brachiocephalic Artery or Ascending Aorta for Low Ejection Fraction, High-Risk Cardiac Surgery
- Anomalous Origin of the Right Pulmonary Artery from the Ascending Aorta in an Adult After Prior Patent Ductus Arteriosus Surgery
- A neonatal extra-anatomical bypass for a “corkscrew” descending aorta associated with interrupted right aortic arch
BibTeX
@article{feng2026alleviate,
title = {{DHA and EPA alleviate atherosclerosis by synergistically regulating the aorta–liver axis via miRNA networks}},
author = {Junli Feng and Yiran Jin and Yu Zhang and Yibin Mei and Yibin Pan and Qing Shen and Chunlai Zeng and Yong Cui and Ning Huangfu},
journal = {npj Science of Food},
year = {2026},
month = jun,
doi = {10.1038/s41538-026-00920-6},
url = {https://doi.org/10.1038/s41538-026-00920-6},
note = {CC BY},
}
RIS
TY - JOUR
TI - DHA and EPA alleviate atherosclerosis by synergistically regulating the aorta–liver axis via miRNA networks
AU - Junli Feng
AU - Yiran Jin
AU - Yu Zhang
AU - Yibin Mei
AU - Yibin Pan
AU - Qing Shen
AU - Chunlai Zeng
AU - Yong Cui
AU - Ning Huangfu
PY - 2026
DA - 2026/06/01
JO - npj Science of Food
DO - 10.1038/s41538-026-00920-6
UR - https://doi.org/10.1038/s41538-026-00920-6
AB - The anti-atherosclerotic effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are well-documented, yet the underlying molecular mechanisms, particularly via cross-organ crosstalk, remain unclear. Here, a high-fat diet-induced atherosclerosis (AS) model in ApoE –/– mice was constructed. Compared with controls, AS mice exhibited elevated serum total cholesterol, triglyceride and low-density lipoprotein cholesterol levels, along with reduced high-density lipoprotein cholesterol levels, impaired hepatic and cardiac function, enlarged aortic plaque area, and pronounced hepatic steatosis and cardiac lipid deposition. DHA/EPA intervention reversed these biochemical and histopathological abnormalities, and conferred superior hepatoprotection than Atorvastatin. Transcriptomics identified 1453 and 1663 differentially expressed genes in liver and aorta of AS mice, respectively. DHA/EPA up-regulated genes related to hepatic cholesterol metabolism and bile acid synthesis, and aortic genes encoding ABC transporters and PPAR signaling components. Conversely, they suppressed hepatic IL-17 signaling and endothelial adhesion molecules. MicroRNA quantification showed significant modulation of aortic miR-33a, miR-146a-3p, miR-155 and miR-223-3p levels, implicating regulation of lipid metabolism and inflammation. Collectively, these data indicate that DHA and EPA exert synergistic anti-atherosclerotic effects via the aorta-liver axis, regulating lipid metabolism, inflammation and vascular remodeling via a miR-30a/146a-3p/223-3p mediated network. These findings provide experimental and mechanistic supports for nutritional intervention of AS.
SN - 2396-8370
ER -