Extracellular vesicle-derived miR-146a as a novel crosstalk mechanism for high-fat induced atherosclerosis by targeting SMAD4

Kefeng Zhai ¹, Liangle Deng ², Yuxuan Wu ²

¹School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou, Anhui 234000, China; College of Biological and Food Engineering, Anhui Polytechnic University, Wuhu, Anhui 241000, China; General Clinical Research Center, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou 234000, China.
²School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou, Anhui 234000, China.
³School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou, Anhui 234000, China; College of Biological and Food Engineering, Anhui Polytechnic University, Wuhu, Anhui 241000, China.
⁴School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou, Anhui 234000, China; Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo-Ourense Campus, Ourense E-32004, Spain.
⁵School of Pharmacy, Wannan Medical College, Wuhu, Anhui 241002, China.
⁶Department of Pharmacology and Therapeutics, Faculty of Pharmacy, University of Central Punjab, Lahore 54000, Pakistan.
⁷International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China; Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi Arabia.
⁸General Clinical Research Center, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou 234000, China.
⁹School of Biological Science and Engineering, North Minzu University, Yinchuan 750021, China.

⁰School of Biological and Food Engineering, Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, Suzhou University, Suzhou, Anhui 234000, China; College of Biological and Food Engineering, Anhui Polytechnic University, Wuhu, Anhui 241000, China; General Clinical Research Center, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou 234000, China.

Journal of Advanced Research +

|

August 10, 2024

View abstract on PubMed

Summary

Exosomes carrying miR-146a promote atherosclerosis by targeting SMAD4 and activating the p38 MAPK pathway. Inhibiting miR-146a effectively reduced atherosclerosis in mice, suggesting its therapeutic potential.

Area Of Science

Cardiovascular Research
Molecular Biology
Cell Biology

Background

Exosome-miR-146a is elevated in atherosclerosis (AS) patients.
The precise role and mechanism of exosome-miR-146a in AS remain unclear.

Purpose Of The Study

Investigate exosome release mechanisms.
Elucidate the role and molecular mechanisms of exosome-miR-146a in AS.

Main Methods

Isolated exosomes from ox-LDL treated macrophages.
Identified exosome release regulators (NMMHC IIA, HSP70).
Assessed exosome uptake and effects on HVSMCs.
Determined miR-146a targets (SMAD4) and pathway modulation (p38 MAPK).
Utilized a mouse model of AS to evaluate exosome-miR-146a impact.

Main Results

Foam cells showed increased miR-146a expression.
Exosomes from macrophages were internalized by HUVECs.
miR-146a directly targeted SMAD4, modulating the p38 MAPK pathway and causing HUVEC damage.
Exosome-miR-146a promoted HVSMC proliferation and migration.
Inhibition of miR-146a reduced AS in mice, while its increase worsened AS.

Conclusions

Exosome-miR-146a plays a critical role in AS pathogenesis.
miR-146a is a potential therapeutic target for AS.
Further research is needed to understand in vivo exosome-miR-146a regulation for therapeutic strategies.

Keywords:

Atherosclerosis Foam cells NMMHC II A SMAD4 exosome-miR-146a

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