A Systematic Review and Meta-Analysis of the Association between Residual Shunts after Patent Foramen Ovale Closure and Long-Term Cerebrovascular Events.

BACKGROUND: The association between a patent foramen ovale (PFO) and cryptogenic stroke (CS) is well established, and the benefits of PFO closure are clearly recognized. This study aimed to investigate the presence of a residual shunt in patients who have experienced cryptogenic cerebrovascular events following a PFO closure. METHODS: Two researchers systematically searched the PubMed and Embase online database for pertinent clinical studies published between January 2000 and July 2021 concerning the recurrence of cerebrovascular events after PFO closures. RESULTS: Upon screening an initial list of 2,342 articles, six studies were identified, involving 2,083 patients. Overall, the analysis indicated a marked difference in the recurrence of cerebrovascular events in 8.89% of residual shunt (RS) cases compared to only 2.90% of non-RS cases. The summary odds ratio was 3.484 (95% confidence interval, 2.169-5.596), which suggested that RS may be a risk factor for recurrent cerebrovascular events in patients that experienced PFO-related cerebrovascular events within 6 months after PFO closure surgery. CONCLUSIONS: The presence of RS significantly increases the risk of recurrent cerebrovascular events in patients with clinical PFO closure.

Sacubitril/valsartan inhibits ox­LDL­induced MALAT1 expression, inflammation and apoptosis by suppressing the TLR4/NF­κB signaling pathway in HUVECs.

The therapeutic effect of sacubitril/valsartan (S/V) on heart failure has been confirmed, while its role in atherosclerosis remains largely unexplored. The present study aimed to investigate the effects of S/V on the expression of metastasis­associated lung adenocarcinoma transcript 1 (MALAT1), inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) induced by oxidized low­density lipoprotein (ox­LDL) and to elucidate its possible mechanism. Cell Counting Kit­8 assay was used to detect cell viability. Reverse transcription­quantitative PCR was performed to detect the MALAT1 expression. ELISA was performed to detect the levels of IL­1ß, IL­6 and TNF­α. Flow cytometry was conducted to detect the apoptotic rate of cells. A nitric oxide (NO) detection kit was used to determine the concentration of NO. Western blotting analysis was performed to determine the levels of intercellular cell adhesion molecule (ICAM)­1, vascular cell adhesion molecule (VCAM)­1, endothelin­1, caspase­3, Bax, Bcl­2, Toll­like receptor 4 (TLR4), p65 and p­p65. Compared with the ox­LDL group, S/V treatment significantly increased the cell viability, NO concentration and Bcl­2 expression, decreased the levels of IL­1ß, IL­6 and TNF­α and reduced the expressions of MALAT1, ICAM­1, VCAM­1, cleaved­caspase­3, Bax, TLR4 and p­p65. Overall, the findings suggested that S/V could downregulate the expression of MALAT1, inhibit inflammation and apoptosis and improve endothelial function in ox­LDL­induced HUVECs via inactivating the TLR4/NF­κB signaling pathway. Therefore, S/V might be utilized as a promising therapeutic strategy for the prevention and treatment of atherosclerosis.