Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway.

Circular RNA (circRNA) is involved in the pathogenesis of atherosclerosis (AS). The present work analyzed the RNA expression of circ_0113656, microRNA-188-3p (miR-188-3p), and insulin-like growth factor 2 (IGF2) by quantitative real-time polymerase chain reaction. The protein expression of proliferating cell nuclear antigen (PCNA), matrix metalloprotein 2 (MMP2), and IGF2 was detected by Western blotting. Cell viability, proliferation, invasion, and migration were analyzed using the cell counting kit-8, 5-ethynyl-2'-deoxyuridine, transwell invasion, and wound-healing assays, respectively. The interactions among circ_0113656, miR-188-3p, and IGF2 were identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. The results showed that circ_0113656 and IGF2 expression were significantly upregulated, while miR-188-3p was downregulated in the blood of AS patients and oxidized low-density lipoprotein (ox-LDL)-treated HVSMCs in comparison with controls. The ox-LDL treatment induced HVSMC proliferation, migration, and invasion accompanied by increases in PCNA and MMP2 expression; however, these effects were attenuated after circ_0113656 knockdown. Circ_0113656 acted as a miR-188-3p sponge and it regulated ox-LDL-induced HVSMC disorders by binding to miR-188-3p. Besides, the regulation of miR-188-3p in ox-LDL-induced HVSMC injury involved IGF2. Further, the depletion of circ_0113656 inhibited IGF2 expression by interacting with miR-188-3p. Thus, the circ_0113656/miR-188-3p/IGF2 axis may mediate ox-LDL-induced HVSMC disorders in AS, providing a new therapeutic strategy for AS.

Identification of key programmed cell death-related genes and immune infiltration in extracorporeal membrane oxygenation treatment for acute myocardial infarction based on bioinformatics analysis.

Background: Extracorporeal membrane oxygenation (ECMO) is an important clinical treatment for acute myocardial infarction (AMI) combined with cardiogenic shock, but the role of programmed cell death (PCD)-related genes in prognostication has not yet been investigated. Therefore, we explored the key prognostic biomarkers and immune infiltration in ECMO treatment in AMI combined with cardiogenic shock. Methods: The GSE93101 dataset was analyzed from the Gene Expression Omnibus (GEO) database, and the expression levels of PCD-related genes in AMI under ECMO were identified. Differentially expressed PCD-related genes between successful and failed treatment samples were analyzed, and Least absolute shrinkage and selection operator (LASSO) logistic regression and random forest were used to screen PCD-related molecular markers for ECMO treatment in AMI combined with cardiogenic shock. Co-expressed regulatory network and enrichment functions of the hub PCD-related genes were performed. In addition, the single-sample gene set enrichment analysis (ssGSEA) algorithm was used to calculate the immune cell infiltration of the ECMO treatment samples. Results: A total of 115 differentially expressed genes were identified from the GSE93101 dataset, and 76 genes were associated with PCD. Then, two hub PCD-related genes, Cell division cycle associated 7 (CDCA7), ankyrin repeat and SOCS box containing 13 (ASB13) were identified as prognostic markers of ECMO treatment in AMI combined with cardiogenic shock. The most significant Gene Ontology (GO) enriched terms of the co-expressed protein of ASB13 are related to post-translational protein modification, cullin-RING ubiquitin ligase complex, and cullin family protein binding, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that ubiquitin mediated proteolysis is the most enriched pathway. The results of GO and KEGG analysis in CDCA7 were mainly involved in DNA and cell cycle related activities and pathways. Moreover, we found that the successful treatment samples contained a lower proportion of nature killer T cells using immune infiltration analysis. Immune cell infiltration analysis revealed that ASB13 was positively correlated with natural killer cell (r = 0.591, p = 0.026), monocyte (r = 0.586, p = 0.028), and gamma delta T cell (r = 0.562, p = 0.036). Conclusion: The results of this study showed that ASB13 and CDCA7 may contribute to the occurrence and progression of AMI with cardiogenic shock under ECMO.

Pirfenidone attenuates cardiac hypertrophy against isoproterenol by inhibiting activation of the janus tyrosine kinase-2/signal transducer and activator of transcription 3 (JAK-2/STAT3) signaling pathway.

Cardiovascular risk factors have attracted increasing attention in recent years with the acceleration of population aging, amongst which cardiac hypertrophy is the initiating link to heart failure. Pirfenidone is a promising agent for the treatment of idiopathic pulmonary fibrosis and has recently proven to exert inhibitory effects on the inflammatory response. This study proposes to explore the potential pharmacological action of Pirfenidone in treating cardiac hypertrophy in a rodent model. Four groups of mice were used in the present study: the control, ISO (5 mg/kg/day) for 7 days, Pirfenidone (200 mg/kg/day) for 14 days, and Spironolactone (SPI) (200 mg/kg/day) for 14 days groups. Increased heart weight index, left ventricle (LV) weight index, LV wall thickness, declined LV volume, and elevated serum levels of CK-MB, AST, and LDH were observed in ISO-challenged mice, all of which were dramatically reversed by the administration of Pirfenidone or SPI. Furthermore, an elevated cross-sectional area of cardiomyocytes in the wheat germ agglutinin (WGA) staining of heart cross-sections, upregulated atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), ß Myosin Heavy Chain (ß-MHC), and excessively released tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in cardiac tissues were observed in the ISO group but greatly alleviated by Pirfenidone or SPI. Lastly, the promoted expression levels of p-JAK-2/JAK-2 and p-STAT3/STAT-3 in the cardiac tissues of ISO-challenged mice were significantly repressed by Pirfenidone or SPI. Collectively, our data reveals a therapeutic property of Pirfenidone on ISO-induced cardiac hypertrophy in mice.

Antihypertensive treatment and risk factors for syncope in asymptomatic aortic stenosis patients with hypertension.

BACKGROUND: Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis(AS) is scarce. OBJECTIVES: Given the paucity of data on the relationship between syncope and antihypertensive treatment in aortic stenosis. This study sought to investigate this association in patients admitted to our hospital. METHODS: A total of 158 patients with asymptomatic moderate or severe aortic stenosis were analyzed. Follow-up was conducted by clinic visit, telephone contact, or review of electronic medical records. Outcomes were syncope. RESULTS: Hypertension were documented in 90 of the 158 patients with moderate or severe AS, and 77 of them received antihypertensive medications. During an average 28 months follow-up period, the occurrence of syncope was observed in 13 patients. Among them, 8 were in antihypertensive group (n = 77) and 5 in normotensive group (n = 68). There was no significant difference in incidence of syncope between the two groups. Patients with treated hypertension and syncope had a lower stroke volume index (SVi), a higher valve arterial impedance (ZVA), a smaller SAC than those without. Kaplan-Meier analysis showed that there was no significant difference in syncope cumulative incidence between antihypertensive group and normotensive group (log rank P = .478). Multivariate cox regression analysis showed that both ZVA (hazard ratio:19.006, 95% confidence interval: 4.664 to77.448;P = .002) and LVMI (hazard ratio:1.484, 95% confidence interval: 1.427 to 5.157;P = .016) were associated with development of syncope, whereas hypertension were not related independently to syncope (hazard ratio:0.935, 95% confidence interval: 0.786 to3.173; P = .869). CONCLUSIONS: In patients with moderate or severe AS, concomitant hypertension, and antihypertensive treatment didn't increase the occurrence of syncope, whereas higher ZVA was independently associated with greater risk of syncope.

Effects of geranylgeranylacetone upon cardiovascular diseases.

Heat shock proteins (HSPs) are an important family of protective proteins. They are involved actively in an array of cellular processes, including protective effects on the cardiovascular system in response to various stimuli. Increasing evidence shows that pharmacologic interventions that induce expression of HSPs may be a novel approach for the treatment of cardiovascular diseases. However, agents that induce expression of HSPs used previously are toxic or have harmful side effects, which limit their clinical application. Geranylgeranylacetone (GGA) is not only a widely used antiulcer agent in Asia, but also a nontoxic inducer of HSPs expression. It increases the expression of HSPs rapidly in the presence of ischemia, anoxia, oxidative stress, and toxicants, thereby having significant protective effects. The cardioprotective effects of GGA have been corroborated by experiments in vivo and in vitro. Importantly, several derivatives of GGA have been synthesized that have improved pharmaco-chemical and HSPs-boosting properties. In this review, the current knowledge and potential cardioprotective mechanisms of GGA are summarized comprehensively. We discuss the protective effects of GGA in cardiovascular diseases and myocardial injury induced by physical or chemical injury. Currently available information suggests that GGA could be employed as a novel pharmacologic intervention against cardiovascular disease.