Macrophage polarization is of great importance in the formation of atherosclerotic plaque. Homeobox A5 (HOXA5), one of the homeobox transcription factors, has been revealed to be closely associated with macrophage phenotype switching. This study aims to investigate the role of HOXA5 in carotid atherosclerosis (CAS). Herein, the role of HOXA5 was explored in polarized RAW264.7 macrophages in vitro and ApoE−/− mice in vivo. Interestingly, compared with that in M0 macrophages, both the mRNA and protein expression levels of HOXA5 were decreased in lipopolysaccharide (LPS)/interferon (IFN)‐γ‐induced M1 macrophages, while increased in IL‐4‐induced M2 macrophages. In addition, in the presence of IL‐4, HOXA5‐overexpressing RAW264.7 cells preferred to polarizing toward M2 phenotypes. Furthermore, we found that HOXA5 bound to the promoter region and activated the expression of mediator subunit 1 (MED1), a gene known to regulate macrophage differentiation. Knocking MED1 down inhibited HOXA5‐enhanced M2 macrophage polarization. In vivo, the CAS model was induced in ApoE−/− mouse fed with a Western‐type diet and placed a perivascular carotid collar. Decreased mRNA and protein expressions of HOXA5 were observed in carotid arteries of CAS mice. Forced overexpression of HOXA5 reduced intimal hyperplasia and lipid accumulation in carotid vessels, and it also promoted the polarization of macrophages to M2 subtypes. The expression of MED1 was decreased in atherosclerotic carotid vessels, while HOXA5 overexpression restored its change. Collectively, HOXA5 in carotid arteries is involved in the macrophage M1/M2 switching in atherosclerotic plaque, which may be associated with its transcriptional regulation of MED1.
Background: Plasminogen activator inhibitor-1 (PAI-1) is considered to be involved in the physiopathological mechanisms of Alzheimer's disease (AD), metabolic syndrome (MetS), and female infertility. Previous studies investigating the association between PAI-1 4G/5G (rs1799889) gene polymorphism and the risk of AD, MetS, and female infertility have reported inconsistent results. The aim of the present study was to investigate possible associations. Methods: Eligible studies were retrieved through PubMed, Medline, EMBASE, CNKI, and WANFANG databases. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the associations. Subgroup analyses by ethnicity and mean age, sensitivity analyses, and publication bias were performed. Results: Five studies (four articles) for AD, six studies (six articles) for MetS, and four studies (four articles) for female infertility were included in this meta-analysis. Our results showed no significant associations between the PAI-1 4G/5G polymorphism and the risk of AD and female infertility in five genetic models. For the risk of MetS, the PAI-1 4G/5G (rs1799889) polymorphism may be associated with the risk of MetS (4G vs 5G, OR = 1.31, 95%CI = 1.04–1.64, P = .021), especially in Asians (4G/4G vs 4G/5G+5G/5G, OR = 1.38, 95%CI = 1.01–1.87, P = .041) and patients with mean age > 50 years old (4G/4G vs 4G/5G+5G/5G, OR = 1.36, 95%CI = 1.03–1.78, P = .029). Conclusion: The present meta-analysis suggested that the PAI-1 4G/5G polymorphism might be associated with the risk of MetS, but no evidence was detected for AD and female infertility.
Background The association between polymorphisms in vitamin D-binding protein (DBP) gene and the risk of multiple sclerosis (MS) and type 1 diabetes mellitus (T1DM) has been investigated in many studies, but the studies showed controversial results. The rationale for this meta-analysis was to determine whether DBP polymorphisms increases the risk of MS and T1DM by pooling data. Methods Potentially relevant studies were searched using GWAS Catalog, PubMed, Embase, CNKI and WANFANG databases up to November 2019. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were performed to estimate the associations in a fixed-effects or random-effects model. Results A total of 13 studies were enrolled in this meta-analysis, including eight studies for MS and five for T1DM. The overall results showed that there was no significant association of DBP rs7041 and rs4588 polymorphisms with the risk of MS and T1DM under any genetic model. Similarly, subgroup analysis by ethnicity revealed that no significant association of rs7041 and rs4588 polymorphisms with the risk of MS and T1DM was observed in white or non-white racial groups. Conclusions This meta-analysis provides evidence that DBP rs7041 and rs4588 polymorphisms may not be associated with an increased risk in MS and T1DM. However, these findings need further validation by larger-scale epidemiological studies and genome-wide association studies (GWASs) in different populations.
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