郭文玉
深圳市孙逸仙心血管医院 心血管内科
This study examined the effects of Stmn2 on phenotype transformation of vascular smooth muscle in vascular injury via RNA sequencing and experimental validation. Total RNA was extracted for RNA sequencing after 1, 3 and 5 days of injury to screen the differentially expressed genes (DEGs). Western blot was used to detect the protein expression of Stmn2 and its associated targets. The morphological changes of carotid arteries in rats were examined by hematoxylin and eosin (H&E) staining. The expression of vascular smooth muscle cell (VSMC) phenotype markers smooth muscle alpha-actin (α-SMA), vimentin and OPN were detected by immunohistochemistry. DEGs were related to the extracellular matrix and other cell components outside the plasma membrane. They were associated with protein binding, cytoskeleton protein binding, signal receptor binding and other molecular functions, actin cytoskeleton regulation and other Kyoto Encyclopedia of Genes and Genomes pathways. Stmn2 was identified as the hub gene of actin cytoskeleton pathway and vascular disease, and its expression followed the trend of decreasing initially and increasing afterwards during the progress of vascular injury. Western blot assay showed that the expression of Stmn2 and Tubulin decreased immediately after vascular injury; Stmn2 overexpression significantly up-regulated the expression of osteopontin and α-SMA and vimentin in VSMCs. The results of morphology analysis and immunostaining also showed that Stmn2 overexpression promoted the intima thickening and enhanced the proliferating cell nuclear antigen expression in the injured vascular tissues. In conclusion, our results implied that Stmn2 may play a potential role in vascular injury, which may be associated with VSMC phenotype transformation. Further studies are warranted to determine detailed molecular mechanisms of Stmn2 in vascular injury.
Environmental science and pollution research international 2022
Introduction:Myocardial ischemia/reperfusion (I/R) injury is a leading cause of cardiac dysfunction. Circular RNAs (circRNAs) are involved in the pathogenesis of myocardial I/R injury. However, the functions and underlying mechanisms are unclear. The present study determined the role of circ-RHOJ.1 in regulating myocardial cell proliferation and apoptosis after I/R injury.Material and methods:Myocardial cells isolated from Sprague-Dawley rats were identified with an immunofluorescence assay using cardiac troponin T antibody. Expression of circ-RHOJ.1, miR-124-3p and neuregulin-1 (NRG1) mRNA was assessed with real-time quantitative polymerase chain reaction. NRG1 protein expression was evaluated with western blot and immunofluorescence assays. Dual-luciferase reporter assay was performed to confirm interaction between miR-124-3p and circ-RHOJ.1, and miR-124-3p and NRG1. Effects of circ-RHOJ.1 overexpression or miR-124-3p inhibition on cell proliferation and apoptosis were evaluated using cell counting kit (CCK)-8 assay and flow cytometry. Cytokines levels were analyzed with an enzyme-linked immunosorbent assay.Results:Myocardial cells were successfully isolated and had down-regulated expression of circ-RHOJ.1 and NRG1, and up-regulated expression of miR-124-3p after I/R injury. circ-RHOJ.1 acted as a sponge for miR-124-3p, and NRG1 served as a target gene of miR-124-3p. circ-RHOJ.1 overexpression or miR-124-3p inhibition increased interleukin (IL)-10 levels and reduced IL-2, IL-6, and tumor necrosis factor-α levels in myocardial cells after I/R injury. Functional assay results illustrated that circ-RHOJ.1 overexpression or miR-124-3p inhibition enhanced proliferation and inhibited apoptosis of myocardial cells after I/R injury.Conclusions:Circ-RHOJ.1 served as a molecular marker of myocardial I/R injury via regulation of miR-124-3p and NRG1 expression.
Archives of medical science : AMS 2022
BACKGROUND:Previous studies have shown that the lactate/albumin (L/A) ratio plays a role in predicting the outcomes of septic shock or severe sepsis. However, the role of the L/A ratio in predicting the outcomes of critically ill patients with heart failure remains unclear. We therefore performed a retrospective study to clarify this issue.METHODS:The study was based on the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database and included critically ill adult patients with heart failure. The primary endpoints were 28-day and 1-year all-cause mortality after admission at the intensive care unit.RESULTS:We analyzed 4,562 patients in this study. We divided the participants into five groups according to the L/A ratio: quintile (Q)1 (L/A ratio ≤0.40, n=913), Q2 (0.40< L/A ratio ≤0.51, n=912), Q3 (0.51< L/A ratio ≤0.66, n=912), Q4 (0.66< L/A ratio ≤0.92, n=912), and Q5 (L/A ratio >0.92, n=913). After stratifying by L/A ratio, the risk of 28-day and 1-year mortality were significantly different between the groups (log-rank P<0.001). Compared with the first quintile, the second, third, fourth, and fifth quintiles of the L/A ratio were associated with higher 28-day [hazard ratio (HR) 1.57, 95% confidence interval (CI): 1.21-2.03 for Q3, HR 1.72, 95% CI: 1.34-2.21 for Q4, and HR 3.15, 95% CI: 2.47-4.01 for Q5) and 1-year mortality (HR 1.19, 95% CI: 1.00-1.41 for Q2, HR 1.36, 95% CI: 1.15-1.60 for Q3, HR 1.42, 95% CI: 1.20-1.67 for Q4, and HR 2.46, 95% CI: 2.09-2.89 for Q5). The restricted cubic spline showed that the L/A ratio positively correlated with both 28-day and 1-year all-cause mortality.CONCLUSIONS:The L/A ratio could serve as a predictor of short and long-term mortality in critically ill patients with heart failure.
Annals of translational medicine 2021
Acute myocardial infarction (AMI) represents a severe coronary heart disease with relatively high rate of mortality and usually can lead to the damage of the myocardial tissues. Reperfusion of the ischemic myocardial tissues can minimize AMI-induced damage. As far as we know, the molecular mechanisms underlying ischemia/reperfusion (I/R)-induced injury remains elusive. This study was undertaken to explore the role of miR-1247-3p in regulating myocardial I/R injury. The hypoxia/reoxygenation (H/R)-treated H9c2 cells showed a decreased cell viability and mitochondrial membrane potential with an increase in the apoptosis; furthermore, miR-1247-3p was down-regulated in these cells. MiR-1247-3p overexpression attenuated H/R-induced H9c2 cell injury; while miR-1247-3p knockdown in H9c2 cells exhibited similar effects being observed in H/R-treated cells. The bioinformatics prediction revealed Bcl-2-like protein 11 (BCL2L11) and caspase-2 were two potential targets for miR-1247-3p, and functional assays confirmed that miR-1247-3p targeted both BCL2L11 and caspase-2 3' untranslated regions, which lead to the repressed expression of these genes. Silencing of BCL2L11 and caspase-2 both, respectively, counteracted the H9c2 cell injury caused by H/R treatment. Moreover, BCL2L11 and caspase-2 overexpression, respectively, impaired the protective effects of miR-1247-3p overexpression on H/R-treated H9c2 cells. The data in the present investigation revealed that miR-1247-3p restoration exhibited protective effects on H/R-induced cardiomyocyte injury through targeting BCL2L11 and caspase-2, implying that miR-1247-3p along with caspase-2/BCL2L11 signaling may provide novel sight for a better understating of I/R-induced myocardial damage. The role of miR-1247-3p might be further confirmed in animal models and clinical studies.
Journal of receptor and signal transduction research 2021
AIMS:The triglyceride glucose (TyG) index is a marker of insulin resistance. However, the prognostic value thereof in patients with chronic heart failure (CHF) and type 2 diabetes remains unclear.METHODS:This study included patients diagnosed with CHF and type 2 diabetes in Fuwai Hospital of Chinese Academy of Medical Sciences, Shenzhen, from January 2017 to July 2019. The primary endpoint was cardiovascular death or rehospitalization for heart failure.RESULTS:The study included 546 patients with CHF and type 2 diabetes. We divided the patients into three groups (T1 [TyG index < 8.55], T2 [TyG index ≥ 8.55 and < 9.06], and T3 [TyG index ≥ 9.06]) according to the TyG index level. The incidence of the primary outcome in the T3 group was significantly higher than that in the T1 group. There was no significant difference between the T1 and T2 groups. The trend test revealed a positive correlation between the TyG index and the incidence of the primary outcome (P = 0.001).CONCLUSIONS:There is a positive correlation between the TyG index and the prognosis of patients with CHF and type 2 diabetes.
Diabetes research and clinical practice 2021
AIMS:The relationship between baseline base excess (BE) and survival outcomes in patients with congestive heart failure (CHF) is unclear. Therefore, we aimed to investigate this relationship based on the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database (v1.4).METHODS AND RESULTS:This retrospective cohort study included 5956 adult patients with CHF from the MIMIC-III database from 2001 to 2012. Using the Cox proportional-hazard analysis and Kaplan-Meier plot, we evaluated the relationship between baseline BE and all-cause death at 1 year after admission to the intensive care unit. At the 1 year follow-up, 2104 participants (35.3%) had died. There was an association between BE and all-cause death (log-rank test P < 0.0001). In the Cox regression model adjusted for demographic and clinical variables, the risk of all-cause death in the first (BE ≤ -8), second (-8 < BE ≤ -3), fourth (2 < BE ≤ 7), and fifth (BE > 7) BE groups was significantly higher than that in the third BE group (-3 < BE ≤ 2) [hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.62-2.43, HR 1.40, 95% CI 1.23-1.60, HR 1.46, 95% CI 1.26-1.69, and HR 1.68, 95% 1.33-2.12, respectively]. Similar results were observed when BE was modelled as a continuous variable using a Cox regression model with a restricted cubic spline.CONCLUSIONS:This study demonstrated the existence of a U-shaped relationship between BE and survival outcome in patients with CHF. Both low and high BE increased the risk of all-cause mortality.
ESC heart failure 2021
