Icariside II Restores Vascular Smooth Muscle Cell Contractile Phenotype by Enhancing the Focal Adhesion Signaling Pathway in the Rat Vascular Remodeling Model.

Vascular smooth muscle cell (VSMC) phenotypic transition represents the fundamental pathophysiological alteration in the vascular remodeling process during the initiation and progression of cardiovascular diseases. Recent studies have revealed that Icariside II (ICS-II), a flavonol glycoside derived from the traditional Chinese medicine Herba Epimedii, exhibited therapeutic effects in various cardiovascular diseases. However, the therapeutic efficacy and underlying mechanisms of ICS-II regarding VSMC phenotypic transition were unknown. In this study, we investigated the therapeutic effects of ICS-Ⅱ on vascular remodeling with a rat's balloon injury model in vivo. The label-free proteomic analysis was further implemented to identify the differentially expressed proteins (DEPs) after ICS-II intervention. Gene ontology and the pathway enrichment analysis were performed based on DEPs. Moreover, platelet-derived growth factor (PDGF-BB)-induced primary rat VSMC was implemented to verify the restoration effects of ICS-II on the VSMC contractile phenotype. Results showed that ICS-II could effectively attenuate the vascular remodeling process, promote SMA-α protein expression, and inhibit OPN expression in vivo. The proteomic analysis identified 145 differentially expressed proteins after ICS-II intervention. Further, the bioinformatics analysis indicated that the focal adhesion signaling pathway was enriched in the ICS-II group. In vitro studies showed that ICS-II suppressed VSMC proliferation and migration, and promoted VSMC contractile phenotype by modulating the focal adhesion signaling pathway. Taken together, our results suggest that ICS-II attenuates the vascular remodeling process and restores the VSMC contractile phenotype by promoting the focal adhesion pathway.

Therapeutic efficacy of mesenchymal stem cells for abdominal aortic aneurysm: a meta-analysis of preclinical studies.

BACKGROUND: Abdominal aortic aneurysm (AAA) is life-threatening, surgical treatment is currently the only clinically available intervention for the disease. Mesenchymal stem cells (MSCs) have presented eligible immunomodulatory and regenerative abilities which showed favorable therapeutic efficacy in various cardiovascular diseases. However, current evidence summarizing the effectiveness of MSCs for AAA is lacking. Thus, a meta-analysis and systematic review was necessary to be performed to assess the therapeutic efficacy of MSCs for AAA in preclinical studies. METHODS: Comprehensive literature search restricted in English was conducted in PubMed, Cochrane Library, EBSCO, EMBASE and Web of Science from inception to Oct 2021. The primary outcomes were parameters about aortic diameter change during MSCs intervention. The secondary outcomes included elastin content and expression level of inflammatory cytokines, matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). Data were extracted and analyzed independently by two authors. The meta package with random effects model was used to calculate the pooled effect size and 95% confidence intervals in R (version 4.0.2). RESULTS: Meta-analysis of 18 included studies demonstrated that MSCs intervention has significant therapeutic effects on suppressing aortic diameter enlargement compared with the control group (diameter, SMD = - 1.19, 95% CI [- 1.47, - 0.91]; diameter change ratio, SMD = - 1.36, 95% CI [- 1.72, - 1.00]). Subgroup analysis revealed differences between MSCs and control group regarding to cell type, intervention route and cell compatibility. Moreover, the meta-analysis also showed that MSCs intervention had a significant effect on preserving aortic elastin content, reducing MCP-1, TNF-α, IL-6, MMP-2/9 and increasing TIMP-1/2 expression level compared with control group. CONCLUSION: Our results suggested that MSC intervention is effective in AAA by suppressing aortic diameter enlargement, reducing elastin degradation, and modulating local immunoinflammatory reactions. These results are important for the systemic application of MSCs as a potential treatment candidate for AAA in further animal experiments and clinical trials.

POU class 2 homeobox associating factor 1 (POU2AF1) participates in abdominal aortic aneurysm enlargement based on integrated bioinformatics analysis.

Abdominal aortic aneurysm (AAA) is life-threatening, its natural course is progressively sac expansion and rupture. Elegant studies have been conducted to investigate the molecular markers associated with AAA growth and expansion, this topic however, still needs to be further elucidated. This study aimed to identify potential genes for AAA growth and expansion based on comprehensive bioinformatics approaches. Firstly, 29 up-regulated genes were identified through DEGs analysis between large AAA and small AAA in GSE57691. Secondly, signed WGCNA analysis was conducted based on GSE57691 and the green module was found to exhibit the topmost correlation with large AAA as well as AAA, 133 WGCNA hub genes were further identified. Merged gene set including 29 up-regulated DEGs and 858 green module genes was subjected to constructing a PPI network where 195 PPI hub genes were identified. Subsequently, 4 crucial genes including POU2AF1, FCRLA, CD79B, HLA-DOB were recognized by Venn plot. In addition, by using GSE7084 and GSE98278 for verification, POU2AF1 showed potential diagnostic value between AAA and normal groups, and exhibited a significant higher expression level in large AAA samples compared with small AAA samples. Furthermore, immunohistochemistry results indicated up-regulation of POU2AF1 in large AAA samples than small AAA samples, which implies POU2AF1 may be a key regulator in AAA enlargement and growth. In summary, this study indicates that POU2AF1 has great predictive value for the expansion of AAA, and may contribute to the further exploration of pathogenesis and progression of AAA.