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Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
hUC-MSCs mitigate atherosclerosis induced by a high-fat diet in ApoE-/- mice by regulating the intestinal microbiota
Lin Yang1, Bing Xia1, Tianbao Qian2
1School of Forensic Medicine, Guizhou Medical University, Guiyang, 550000, Guizhou, China.
Background:
The mechanism underlying human umbilical cord mesenchymal stem cells (hUC-MSCs) regulating the stability of atherosclerotic plaque was explored by establishing mice models of atherosclerosis induced by a high-fat diet and hUC-MSCs intervention.
Methods:
The ApoE-/- mice atherosclerosis model was constructed using a high-fat diet, and mice were divided into a normal diet group (ND), high-fat diet group (HFD), hUC-MSCs treatment group (HFDM), while the blank control (BC) consisted of C57BL/6J mice. After successful establishment of the model, the feces, hearts, and aorta of mice were collected. Morphological features were detected using HE, oil red O, and Masson staining. Afterward, 16s rRNA gene sequences was used to detect the species and abundance of the intestinal flora in mice, and an atomic force microscope (AFM) was used to detect the Young's modulus of the fibrous cap of atherosclerotic plaques. Lastly, the expression level of the inflammatory factors NLRP3, IL-1β, and IL-18 were detected via immunohistochemistry and immunofluorescence assays.
Results:
In terms of morphological characteristics, the expression level of NLRP3, Young's modulus of the fibrous cap, and plaque stability were significantly reduced in HFD, whereas the ratio of Firmicutes to Bacteroidetes (F/B) was significantly increased. Interestingly, hUC-MSCs treatment reversed the above indices, thus enhancing plaque stability.
Conclusion:
HFD led to dysregulation of intestinal flora homeostasis and induced aberrant expression levels of NLRP3, resulting in a decrease in the Young's modulus of plaques. However, hUC-MSCs treatment improved the biomechanical properties of plaque by modulating the intestinal flora and NLRP3, thereby elevating plaque stability and minimizing the risk of plaque rupture.
Insights
Human umbilical cord mesenchymal stem cells (hUC-MSCs) enhance atherosclerotic plaque stability by modulating gut microbiota and reducing inflammation. This intervention improves biomechanical properties, minimizing rupture risk.
Area of Science:
- Cardiovascular Biology
- Stem Cell Therapy
- Microbiome Research
Background:
- Atherosclerosis is characterized by plaque instability, increasing rupture risk.
- High-fat diets (HFD) disrupt gut microbiota and promote inflammation, contributing to plaque instability.
- Human umbilical cord mesenchymal stem cells (hUC-MSCs) are investigated for their therapeutic potential in cardiovascular diseases.
Purpose of the Study:
- To investigate the mechanism by which hUC-MSCs regulate atherosclerotic plaque stability.
- To explore the impact of hUC-MSCs on gut microbiota composition and inflammatory markers in an atherosclerosis mouse model.
- To assess the effect of hUC-MSCs on the biomechanical properties of atherosclerotic plaques.
Main Methods:
- Atherosclerosis was induced in ApoE-/- mice using a HFD.
- Mice received hUC-MSCs treatment, and various analyses were performed on collected tissues and fecal samples.
- Methods included histological staining (HE, oil red O, Masson), 16s rRNA gene sequencing for gut microbiota, atomic force microscopy (AFM) for plaque Young's modulus, and immunohistochemistry/immunofluorescence for inflammatory factors (NLRP3, IL-1β, IL-18).
Main Results:
- HFD induced plaque instability, characterized by reduced Young's modulus and increased NLRP3 expression, alongside altered gut microbiota (increased Firmicutes/Bacteroidetes ratio).
- hUC-MSCs treatment reversed these changes, significantly improving plaque morphological characteristics and biomechanical properties.
- hUC-MSCs intervention led to enhanced plaque stability and a reduced Firmicutes to Bacteroidetes ratio.
Conclusions:
- HFD disrupts gut microbiota homeostasis and elevates NLRP3 expression, decreasing plaque biomechanical stability.
- hUC-MSCs treatment ameliorates plaque instability by modulating gut microbiota and NLRP3 expression.
- hUC-MSCs improve plaque biomechanical properties, thereby enhancing stability and reducing the risk of plaque rupture.
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