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Correlation between decreased plasma miR-29a and vascular endothelial injury induced by hyperlipidemia

Korrelation zwischen verringertem Plasma-miR-29a-Wert und durch Hyperlipidämie induzierten vaskulären endothelialen Läsionen

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Abstract

Background

Hyperlipidemia is a major risk factor for vascular endothelial injury and atherosclerosis leading to cardiovascular diseases. Early diagnosis of vascular endothelial injury is important for the prevention and prognosis of cardiovascular diseases. This study aimed to investigate sensitive circulating microRNA (miRNA) as a potential diagnostic biomarker of vascular endothelial injury in a hyperlipidemic rat model.

Methods

The miRNA expression profile was detected by miRNA microarray. The hyperlipidemic rat model was established by intraperitoneal injection of vitamin D3 combined with a high-fat diet. Plasma miRNA levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).

Results

No significant difference was found in the types of highly expressed miRNAs between human umbilical artery endothelial cells (HUAEC) and human umbilical vein endothelial cells (HUVEC). A total of 10 highly expressed miRNAs in endothelial cells were selected as candidate miRNAs, including miR-21, miR-126, let-7a, miR-23a, miR-221, miR-125b, miR-26a, miR-29a, miR-16, and miR-100. The plasma levels of let-7a, miR-126, miR-21, and miR-26a were significantly elevated in hyperlipidemic rats at 30 and 50 days after modeling, while the plasma level of miR-29a was significantly decreased. No significant change was found in the plasma levels of miR-125b, miR-23a, miR-221, miR-100, and miR-16. Interestingly, a significant reduction in plasma miR-29 level was detected as early as 20 days after modeling, which was earlier than for soluble intercellular adhesion molecule‑1 (sICAM-1).

Conclusion

The plasma levels of endothelial cell-enriched miRNAs were correlated with vascular endothelial injury induced by hyperlipidemia. miR-29a might serve as a potential early diagnostic biomarker of endothelial injury-related diseases.

Zusammenfassung

Hintergrund

Hyperlipidämie ist ein wesentlicher Risikofaktor für vaskuläre endotheliale Läsionen und Arteriosklerose, die zu kardiovaskulären Erkrankungen führen können. Eine frühe Diagnosestellung hinsichtlich der vaskulären endothelialen Läsionen ist wichtig für die Prävention und Prognose von kardiovaskulären Erkrankungen. Ziel der vorliegenden Studie war es, entsprechend sensitive zirkulierende microRNA (miRNA) als potenziellen diagnostischen Biomarker für vaskuläre endotheliale Läsionen in einem Tiermodell mit hyperlipidämischen Ratten zu untersuchen.

Methoden

Das miRNA-Expressionsprofil wurde mittels miRNA-Microarray bestimmt. Das Tiermodell der hyperlipidämischen Ratten wurde durch eine intraperitoneale Injektion von Vitamin D3 in Kombination mit einer Ernährung mit hohem Fettanteil erzeugt. Plasma-miRNA-Werte wurden durch quantitative Polymerasekettenreaktion unter Nutzung der reversen Transkriptase (qRT-PCR) ermittelt.

Ergebnisse

Zwischen Endothelzellen aus der humanen Nabelschnurarterie (HUAEC) und Endothelzellen aus der humanen Nabelschnurvene (HUVEC) wurden keine wesentlichen Unterschiede in Bezug auf die Typen von miRNA mit hoher Expression festgestellt. Als Kandidaten-miRNA wurden 10 miRNA mit hoher Expression in Endothelzellen ausgewählt, darunter miR-21, miR-126, let-7a, miR-23a, miR-221, miR-125b, miR-26a, miR-29a, miR-16 und miR-100. Die Plasmaspiegel von let-7a, miR-126, miR-21 und miR-26a waren 30 bzw. 50 Tage nach Erzeugung des Tiermodells bei hyperlipidämischen Ratten deutlich erhöht, während der Plasmaspiegel von miR-29a deutlich erniedrigt war. Bei den Plasmaspiegeln von miR-125b, miR-23a, miR-221, miR-100 und miR-16 war keine wesentliche Veränderung festzustellen. Interessant ist, dass eine deutliche Reduktion des Plasmaspiegels von miR-29 bereits 20 Tage nach Erzeugung des Tiermodells beobachtet wurde, was ein früherer Zeitpunkt war als beim löslichen interzellulären Adhäsionsmolekül‑1 (sICAM-1) war.

Schlussfolgerung

Die Plasmaspiegel von in Endothelzellen angereicherten miRNA waren mit vaskulären endothelialen Schädigungen durch Hyperlipidämie korreliert. miR-29a könnte als potenzieller früher diagnostischer Biomarker für Erkrankungen dienen, die mit endothelialen Schädigungen einhergehen.

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Funding

This study was supported in part by the National Key research and Development Planning (2018YFC2002101).

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Authors and Affiliations

  1. Department of Geriatrics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, 200080, Shanghai, China

    Lina An, Min Ning, **ushi Ni, Yiying Wu & Yanhong Gao

  2. Department of Cardiology, Changhai Hospital, Naval medical University, 168 Changhai Road, 200433, Shanghai, China

    Lina An, Feng Wu & Feifei Dong

  3. Department of Cardiovascular Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, 200092, Shanghai, China

    Liming Gao

  4. Key Laboratory of Stem Cell Biology, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), 320 Yueyang Road, 200031, Shanghai, China

    Qing **g

Authors
  1. Lina An
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  2. Liming Gao
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  3. Min Ning
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  4. Feng Wu
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  7. Yiying Wu
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Contributions

Lina An, Liming Gao and Qing **g designed the project; Lina An, Liming Gao, Min Ning, Feng Wu, Feifei Dong and **ushi Ni performed the experiment; Lina An, Liming Gao, Min Ning, Yiying Wu, Qing **g and Yanhong Gao wrote the manuscript.

Corresponding authors

Correspondence to Yiying Wu, Qing **g or Yanhong Gao.

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Conflict of interest

L. An, L. Gao, M. Ning, F. Wu, F. Dong, X. Ni, Y. Wu, Q. **g and Y. Gao declare that they have no competing interests.

For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case.

Additional information

The authors Lina An, Liming Gao and Min Ning contributed equally to the manuscript.

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An, L., Gao, L., Ning, M. et al. Correlation between decreased plasma miR-29a and vascular endothelial injury induced by hyperlipidemia. Herz 48, 301–308 (2023). https://doi.org/10.1007/s00059-022-05121-x

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  • DOI: https://doi.org/10.1007/s00059-022-05121-x

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