miR-33-5p knockdown attenuates abdominal aortic aneurysm progression via promoting target adenosine triphosphate-binding cassette transporter A1 expression and activating the PI3K/Akt signaling pathway.

PURPOSE: The aim of this study was to investigate the role of miR-33-5p in abdominal aortic aneurysm progression, which regulated adenosine triphosphate-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux and lipid accumulation in THP-1 macrophage-derived foam cells through the PI3K/Akt pathway. METHODS: Quantitative reverse transcription polymerase chain reaction was used to evaluate the expression level of miR-33-5p and ABCA1 mRNA in abdominal aortic aneurysm patient and normal person tissues. The relationship between miR-33-5p and ABCA1 was examined by dual luciferase report assay. High-performance liquid chromatography was used to evaluate the levels of cholesterol contents. Cholesterol efflux detection was performed by liquid scintillator. The expression of inflammatory cytokines was detected by quantitative reverse transcription polymerase chain reaction. Western blot was applied to determine the expression levels of ABCA1, PI3K (p-PI3K), and Akt (p-Akt). RESULTS: The quantitative reverse transcription polymerase chain reaction analysis results revealed miR-33-5p overexpression in abdominal aortic aneurysm tissues, but the expression level of ABCA1 was lower in abdominal aortic aneurysm tissues than non-abdominal aortic aneurysm tissues. Subsequently, the dual luciferase report gene assay confirmed that ABCA1 was a target of miR-33-5p, and miR-33-5p-negative regulated ABCA1 expression. Moreover, the expression levels of p-PI3K, p-Akt, and ABCA1 were decreased in THP-1 cell transferred with ABCA1 siRNA, but knockdown of miR-33-5p had an opposite effect. Furthermore, knockdown of miR-33-5p decreased the expression of MMP-2, MMP-9, TNF-α, total cellular cholesterol, and promoted cholesterol efflux in THP-1-derived foam cells. Importantly, LY294002 (PI3K inhibitor) or si-ABCA1 completely inhibited the stimulatory effects of miR-33-5p inhibitor. CONCLUSION: This study has found that knockdown of miR-33-5p induced ABCA1 expression and promoted inflammatory cytokines and cholesterol efflux likely via activating the PI3K/Akt signaling pathway.

Correlation Between ABCA1 Gene Polymorphism and aopA-I and HDL-C in Abdominal Aortic Aneurysm.

BACKGROUND: As the most common type of aneurysm, abdominal aortic aneurysm (AAA) has an unfavorable prognosis due to the high frequency of rupture. Studies have indicated a close relationship between the pathogenesis and progression of AAA and abnormal serum lipid levels. ATP-binding cassette transport protein A1 (ABCA1) is a cell-surface protein facilitating cellular efflux of cholesterol. The single-nucleotide polymorphism (SNP) of ABCA1 gene has been suggested to be correlated with abnormal metabolism of lipids. Therefore, this study aimed to investigate the relationship between ABCA1 polymorphism and apoA-I and HDL-C in an attempt to elucidate its correlation with AAA occurrence. MATERIAL/METHODS: We included 126 AAA patients and 119 healthy controls in this study. PCR and restriction fragment length polymorphism (RFLP) were used to detect the SNP pattern of ABCA1 gene at locus rs2230806 from both AAA patients and healthy controls. The distribution pattern and correlation with apoA-I and HDL-C was analyzed. RESULTS: The distribution of KK/RR genotype of ABCA1 gene had significant difference between disease and control group, with lower rates of RR genotype and R allele in the disease group (p<0.05). Levels of apoA-I and HDL-C, but not triglyceride and LDL-C levels, in AAA patients who carried R allele in ABCA1 gene (including RR and RK genotypes) were higher than in non-carriers (p<0.05). The R allele of ABCA1 gene was shown to be related with the occurrence of AAA (p<0.05). CONCLUSIONS: Polymorphism of ABCA1 gene is correlated with AAA occurrence, possibly via the regulation of serum lipid metabolism by R allele.

Fibrinogen B ß promoter polymorphism may not be associated with pulmonary embolism.

OBJECTIVE: A prospective experiment was designed to explore all possible SNPs in the promoter region of fibrinogen B ß (FGB) and reveal the influence of these SNPs on susceptibility of pulmonary embolism. METHODS: In this 2-year randomized prospective study, we had totally recruited 203 volunteers. 58 PE patients (58 out of 145 VTE patients) and 114 healthy people were taken as case and control objects, respectively. FGB promoter was detected by gene sequencing. RESULTS: There were 6 SNPs in FGB promoter, which were ß-1420G/A, ß-993C/T, ß-854G/A, ß-455G/A, ß-249C/T, and ß-148C/T. Genotype frequencies of individual SNPs between the cases and controls were not statistically significant, all p > .05. After excluding subjects of COVID-19 infection within 6 months, the statistical results (35 PE patients vs 66 healthy people) were consistent. CONCLUSION: The susceptibility to pulmonary embolism may not be affected by any SNP in the FGB promoter region.

The Correlation Between FGB Promoter Polymorphism and Clotting Function in Patients With Idiopathic Lower Extremity Deep Venous Thrombosis.

To explore the possible single nucleotide polymorphisms (SNPs) sites in the promoter region of fibrinogen B ß (FGB), and construct logistic regression model and haplotype model, so as to reveal the influence of FGB promoter SNPs on susceptibility, hemodynamics and coagulation function of lower extremity deep venous thrombosis (LEDVT) in the genetic background. LEDVT patients (120) and healthy people (120) were taken as case and control objects, respectively. SNPs and their genotypes of FGB promoter were detected by promoter sequencing and PCR-RFLP. The parameters of coagulation system were evaluated. There were 6 SNPs in FGB promoter, which were ß-148C/T, ß-249C/T, ß-455G/A, ß-854G/A, ß-993C/T and ß-1420G/A. The genotype and allele frequency of ß-1420 G/A, ß-455G/A, ß-249c/T and ß-148C/T were significantly different between the LEDVT group and the control group, but not ß-993C/T and ß-854G/A. In addition, we found that the higher the content of Fibrinogen (FG), the higher the risk of LEDVT. The risk of LEDVT increased by 4.579 times for every unit increase of fibrinogen. We also found that FG, PT and APTT in LEDVT group were higher than those in control group, while TT was lower than those in control group; Furthermore, there was no significant difference in all coagulation indexes among 6 SNP genotypes in LEDVT group, while a significant difference was found between the 2 genotypes of ß-993C/T in the control group. ß-993C/T may indirectly affect the susceptibility of LEDVT by improving the basic level of plasma FG.