Association of Soluble IL-1 Receptor Type 2 with Recovery of Left Ventricular Function and Clinical Outcomes in Acute Myocardial Infarction.

Background: The role of soluble interleukin-1 receptor type 2 (sIL-1R2) in acute myocardial infarction (AMI) remains undocumented. In the present study, we aimed to evaluate the possible associations of sIL-1R2 with left ventricular (LV) function, remodeling and future clinical events in the setting of AMI. Methods: Circulating sIL-1R2 levels were quantified after percutaneous coronary intervention (PCI) on day 1 of hospital admission for 204 AMI patients, and upon enrollment of 204 healthy controls. Echocardiography was conducted in the acute phase and at 12-month follow-up. Adverse clinical events were registered after 12 months. Results: Circulating sIL-1R2 levels were significantly higher in AMI patients than in healthy controls (medians respectively 6652.81 pg/mL, 3799.13 pg/mL, p < 0.0001). AMI patients with sIL-1R2 levels less than the median had a larger proportion of worsened LV ejection fraction [a decrease in LV ejection fraction (LVEF) of more than 10% units] and reduced LVEF (a final LVEF < 50%). After multivariate adjustment, sIL-1R2 levels less than the median were associated with an increased risk of worsened LVEF [odds ratio (OR): 3.7, 95% confidence interval (CI): 1.6-8.5, p = 0.002] and reduced LVEF at 12 months (OR: 2.1, 95% CI: 1.1-4.3, p = 0.035). Moreover, low sIL-1R2 levels were associated with an increased risk of having an adverse clinical event during the first 12 months after AMI [hazard ratio (HR): 2.5, 95% CI: 1.0-6.1, p = 0.039]. Conclusions: Low levels of circulating sIL-1R2 were associated with impaired recovery of LV function and adverse clinical outcomes in AMI patients. These findings might contribute to understanding the important role of sIL-1R2 in postinfarction inflammation.

LncRNA KCNQ1OT1 Participates in Ox-LDL-Induced Proliferation/Apoptosis Imbalance in Vascular Smooth Muscle Cells by Regulating the MiR-196a-5p/FOXO1 Axis.

Backgroud The present study aimed to investigate the function and regulatory mechanisms of lncRNA KCNQ1OT1 in vascular smooth muscle cells under oxidation low lipoprotein stimulation. Methods RNA sequencing was used to detect transcriptome changes of vascular smooth muscle cells treated with oxidation low lipoprotein. KCNQ1OT1, miR-196a-5p, and FOXO1 expression levels in VSMCs after oxidation low lipoprotein treatment were assessed using qRT-PCR and western blotting. RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter assay were used to confirm the interaction among lncRNA KCNQ1OT1, miR-196a-5p, and FOXO1. The functions of KCNQ1OT1, miR-196a-5p, and FOXO1 were analyzed by CCK-8 and flow cytometry. The serum samples of high fat-feeding mice and atherosclerosis patients were collected, and the levels of KCNQ1OT1 and miR-196a-5p were analyzed. Results In vitro expression of KCNQ1OT1 and FOXO1 decreased in VSMCs treated with oxidation low lipoprotein, accompanied by overexpression of miR-196a-5p. As a ceRNA, KCNQ1OT1 positively regulated FOXO1 and imparted a negative regulatory effect on miR-196a-5p. Interference KCNQ1OT1/miR-196a-5p/FOXO1 could change roliferation/apoptosis imbalance in VSMCs under oxidation low lipoprotein stimulation. Higher levels of KCNQ1OT1 and lower levels of miR-196a-5p can be found in the thoracic aorta tissues of high fat-feeding mice and serum samples from individuals with carotid atherosclerosis. Conclusion Aberrant expression of KCNQ1OT1/miR-196a-5p/FOXO1 pathway mediated oxidation low lipoprotein-induced proliferation/apoptosis imbalance in VSMCs.

ox-LDL regulates proliferation and apoptosis in VSMCs by controlling the miR-183-5p/FOXO1.

BACKGROUND: microRNA-mRNA axes that are involved in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) proliferation/apoptosis imbalance need to be further investigated. OBJECTIVE: To investigate the functional role of miR-183-5p/FOXO1 in VSMCs and its interaction with ox-LDL. METHODS: RNA sequencing was used to detect transcriptome changes of VSMCs treated with ox-LDL. miR-183-5p and FOXO1 expression levels in VSMCs after ox-LDL treatment were assessed using qRT-PCR and western blotting. The regulatory effect of miR-183-5p on FOXO1 has been tried to prove using a dual-luciferase reporter assay. The functions of miR-183-5p, and FOXO1 were analyzed by CCK-8 assay and flow cytometry assay. The tissue samples or serum samples of high fat-feeding mice and carotid atherosclerosis patients were collected, and the levels of miR-183-5p/FOXO1 were analyzed. RESULTS: RNA sequencing data showed 81 miRNAs including miR-183-5p was significantly changed after ox-LDL treatment in VSMCs. FOXO1, a miR-183-5p's potential target, was also down-regulated in ox-LDL treated cells. qRT-PCR and western blot found that expression of FOXO1 mRNA and protein significantly reduced in VSMCs treated with ox-LDL, accompanied by overexpression of miR-183-5p. miR-183-5p inhibited FOXO1 mRNA by binding to its 3' UTR. Interference miR-183-5p/FOXO1 could change proliferation/apoptosis imbalance in VSMCs under ox-LDL stimulation. Higher levels of miR-183-5p but reduced FOXO1 can be found in the thoracic aorta tissues of high fat-feeding mice. In serum samples from individuals with carotid atherosclerosis, Higher levels of miR-183-5p were observed. the miR-183-5p level was positively related to the level of serum ox-LDL in patients. CONCLUSIONS: Aberrant expression of miR-183-5p/FOXO1 pathway mediated ox-LDL-induced proliferation/apoptosis imbalance in VSMCs. The miR-183-5p/FOXO1 axis can potentially be utilized as the target in the treatment of patients with atherosclerosis.

Spontaneous dissection of proximal left main coronary artery in a healthy adolescent presenting with syncope: A case report.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a frequent cause of acute coronary syndrome in young to middle-aged women with few or no traditional cardiovascular risk factors. Chest pain is the most frequently described presenting symptom, but syncope is extremely rare. Herein, we report on a 16-year-old girl who presented with an episode of syncope occurring during a race. Despite significantly elevated troponin level, the diagnosis of the left main coronary artery SCAD with cardiogenic shock was delayed. CASE SUMMARY: A 16-year-old girl presented with an episode of syncope. Myocardial injury markers were positive. Echocardiography showed a mildly reduced left ventricular ejection fraction (50%). Although initially stable, she later experienced recurrent chest pain accompanying precordial ST segment elevation with dynamic changes and developed cardiogenic shock, necessitating emergent revascularization. Coronary angiography demonstrated almost total occlusion at the ostium and proximal segment of the left main trunk coronary artery (LMT). Intravascular ultrasound confirmed a false lumen with prominent dissection in the LMT. Percutaneous coronary intervention assisted by intra-aortic balloon pump was conducted in the LMT. A 3.5 mm × 24 mm everolimus-eluting stent was deployed to the focal lesions of the LMT. A postprocedural electrocardiogram showed alleviation of the precordial ST-segment elevation. The diagnosis of SCAD was confirmed. Transthoracic echocardiography showed an improved left ventricular ejection fraction (57%). The patient was asymptomatic during the 24-mo. follow-up period. CONCLUSION: SCAD should always be considered in the differential diagnosis of acute coronary syndrome presentations in low-risk patients, regardless of age.

Identification and functional analysis of changes to the ox-LDL-induced microRNA-124-3p/DLX5 axis in vascular smooth muscle cells.

BACKGROUND: The microRNA (miR)-mRNA axes involved in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) proliferation/apoptosis imbalance need to be investigated in more detail. OBJECTIVES: To investigate the function and any relevant changes to miR-mRNA axes in the ox-LDL-induced proliferation/apoptosis imbalance in VSMCs. MATERIAL AND METHODS: Human VSMCs were cultured and treated with ox-LDL in vitro. The differentially expressed (DE) miRs and mRNAs in VSMCs following 48-h ox-LDL treatment were detected using RNA sequencing. Candidate miRs and mRNAs were further selected, based on comprehensive bioinformatics analysis. Changes in the expression of candidate miRs and mRNAs in ox-LDL-treated VSMCs were confirmed with quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. The inhibitory effect of candidate miRs on mRNAs were demonstrated using a dual luciferase reporter assay. The functional role of candidate miRs and mRNAs on proliferation, cell cycle and apoptosis of VSMCs were estimated using cell couting kit-8 (CCK-8) and flow cytometry assays, respectively. RESULTS: The RNA sequencing data indicated that 577 mRNAs and 81 miRs were significantly upregulated in VSMCs following ox-LDL treatment. Gene function and pathway enrichment analysis suggested that the DE-mRNAs and miRs participate in the regulation of proliferation, cell cycle and apoptosis. Increased expression of DLX5 with decreasing miR-124-3p levels were confirmed in ox-LDL-treated VSMCs. The miR-124-3p could inhibit the DLX5 level by binding the 3' UTR of DLX5 mRNA. Functional analysis showed that the alteration of miR-124-3p/DLX5 expression mediated the effect of ox-LDL on VSMCs proliferation/apoptosis imbalance. CONCLUSIONS: The ox-LDL affects the VSMC proliferation/apoptosis balance via the miR-124-3p/DLX5 axis, which results in VSMC hyperproliferation. The miR-124-3p/DLX5 axis might serve as a therapeutic molecular target to reverse the effect of ox-LDL and prevent atherosclerosis (AS) development and progression.

[Effect of atorvastatin on ACE2 expression in pressure overload induced cardiac hypertrophy in rats].

OBJECTIVE: To investigate the effect of atorvastatin on the expression of angiotensin converting enzyme 2 (ACE2) mRNA and its protein in hypertrophic myocardium in rats. METHODS: Suprarenal abdominal aortic coarctation was performed to create the pressure overload induced left ventricular hypertrophy model in rats. RESULTS: Rats were randomly divided into 5 groups: (1) normal control group (Group A); (2) normal control group treated with atorvastatin [(5 mg/(kg.dd), Group B]; (3) sham group (Group C); (4) atorvastatin given orally by gastric gavage for 4 weeks [5 mg/(kg.dd),Group D]; (5) vehicle group (Group E). Stained pathological section was observed under light microscope to measure cardiomyocyte diameter transversa and collagen volume fraction. ACE2 mRNA and its protein expression were detected by real-time RT-PCR and Western blot. Compared with Group A,B, and C, the left ventricular mass index, cardiomyocyte diameter transversa and collagen volume fraction in Group E increased statistically (P< 0.01), ACE2 mRNA and its protein expression also elevated remarkably (P< 0.01). Compared with Group E, the above mentioned indexes in Group D reduced significantly (P< 0.01). CONCLUSION: ACE2 mRNA and its protein expression increase significantly in hypertrophic myocardium in rats; atorvastatin can attenuate cardiac hypertrophy due to pressure overload in rats effectively, and part of this anti-hypertrophy effect may be attributed to decrease ACE2 mRNA and protein expression.