# Influence of Atherosclerosis-Associated Risk Factors on Expression of Endothelin Receptors in Advanced Atherosclerosis

**Authors:** Oliver Herbers, Carsten Höltke, Marco Virgilio Usai, Jana Hochhalter, Moushami Mallik, Moritz Wildgruber, Anne Helfen, Miriam Stölting

PMC · DOI: 10.3390/ijms26052310 · International Journal of Molecular Sciences · 2025-03-05

## TL;DR

This study examines how risk factors like hypertension affect the expression of endothelin receptors in advanced atherosclerosis.

## Contribution

The study identifies hypertension as a key factor influencing endothelin receptor expression in atherosclerotic plaques.

## Key findings

- Endothelin receptors and smooth muscle actin are reduced in atherosclerotic plaques.
- Hypertension is strongly correlated with reduced receptor and smooth muscle actin expression.
- Age, BMI, and gender also influence receptor expression, but diabetes and smoking do not.

## Abstract

Endothelin-1 (ET-1) levels are altered in atherosclerosis, while the roles of the endothelin receptors ETAR and ETBR during the pathogenesis of atherosclerosis remain unclear. Therefore, the focus of this study was to clarify how endothelin receptors are expressed in advanced human atherosclerotic plaques and how this is related to atherosclerotic risk factors. Ex vivo expression analysis was performed by quantitative real-time PCR (qRT-PCR) of 98 atherosclerotic plaques and controls that were obtained from adult patients undergoing vascular surgery. Correlation analyses of atherosclerosis-promoting factors were accomplished using a linear regression model. We found an overall reduced expression of ET receptors and smooth muscle actin (SMA), a marker of healthy vascular smooth muscle cells, in atherosclerotic plaques, whereas the levels of ET-1 and matrix metalloproteinase 2 (MMP-2), a marker of atherosclerosis progression, remained unchanged. Reduced expression was predominantly correlated with hypertension, which affects both receptors as well as SMA. Age, body mass index (BMI) and gender also correlated with either ETAR, ETBR or SMA expression in advanced plaques. In contrast, no effect of diabetes mellitus or smoking was found, indicating an ancillary effect of those risk factors. The results of our study indicate that endothelin receptor expression during the pathogenesis of atherosclerosis is predominantly correlated with hypertension.

## Linked entities

- **Genes:** EDNRA (endothelin receptor type A) [NCBI Gene 1909], EDNRB (endothelin receptor type B) [NCBI Gene 1910], SMN1 (survival of motor neuron 1, telomeric) [NCBI Gene 6606]
- **Proteins:** EDN1 (endothelin 1), MMP2 (matrix metallopeptidase 2)
- **Diseases:** atherosclerosis (MONDO:0005311), diabetes mellitus (MONDO:0005015)

## Full-text entities

- **Genes:** MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, EDNRB (endothelin receptor type B) [NCBI Gene 1910] {aka ABCDS, ET-B, ET-BR, ETB, ETB1, ETBR}, EDN1 (endothelin 1) [NCBI Gene 1906] {aka ARCND3, ET1, HDLCQ7, PPET1, QME}, EDNRA (endothelin receptor type A) [NCBI Gene 1909] {aka ET-A, ETA, ETA-R, ETAR, ETRA, MFDA}
- **Diseases:** atherosclerotic plaques (MESH:D058226), hypertension (MESH:D006973), Atherosclerosis (MESH:D050197), diabetes mellitus (MESH:D003920)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11899768/full.md

## References

63 references — full list in the complete paper: https://tomesphere.com/paper/PMC11899768/full.md

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Source: https://tomesphere.com/paper/PMC11899768