Circular RNAs as potential biomarkers and therapeutics for cardiovascular disease

Circular RNAs (circRNAs) are genetic regulators that were earlier considered as “junk”. In contrast to linear RNAs, they have covalently linked ends with no polyadenylated tails. CircRNAs can act as RNA-binding proteins, sequestering agents, transcriptional regulators, as well as microRNA sponges. In addition, it is reported that some selected circRNAs are transformed into functional proteins. These RNA molecules always circularize through covalent bonds, and their presence has been demonstrated across species. They are usually abundant and stable as well as evolutionarily conserved in tissues (liver, lung, stomach), saliva, exosomes, and blood. Therefore, they have been proposed as the “next big thing” in molecular biomarkers for several diseases, particularly in cancer. Recently, circRNAs have been investigated in cardiovascular diseases (CVD) and reported to play important roles in heart failure, coronary artery disease, and myocardial infarction. Here, we review the recent literature and discuss the impact and the diagnostic and prognostic values of circRNAs in CVD

Outcomes Following Coronary Artery Bypass Graft Surgery in Patients with Mild Preoperative Renal Insufficiency

Abstract Introduction: Preoperative renal insufficiency is an independent predictor of mortality after coronary artery bypass graft (CABG) surgery. However, there are few reports aimed to evaluate the impact of mild preoperative renal insufficiency on long-term follow-up outcomes after isolated CABG surgery. This study investigates the effect of mild preoperative renal insufficiency on long-term follow-up outcomes of patients after CABG. Methods: Five hundred eighty-four patients' data that underwent CABG between 1 January 2009 and 1 December 2016 were retrospectively analyzed. They were divided into two groups: normal group [Estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73 m2, n=304] and mild group (eGFR ranges from 60 to 89 ml/min/1.73 m2, n=280). Clinical material and long follow-up outcomes were compared inthe two groups. Results: Two groups had similar baseline and intraoperative data except eGFR. Six (0.01%) patients died in hospital, 15 in normal group and 28 in mild group during the long-term follow-up, which had statistical significance (P<0.05). Univariate factor analysis displayed that the two groups had similar in-hospital outcomes. Kaplan-Meier curves showed a better long-term survival in patients with normal preoperative renal function compared to mild preoperative renal insufficiency (x 2=4.255, P=0.039). Cox proportional model presented the hazard ratio of long-term mortality in patients with mild preoperative renal insufficiency compared to normal preoperative renal function was 1.79 (95% CI 1.17-2.88, P=0.027). Conclusions: Patients with mild preoperative renal insufficiency had a higher mortality rate than normal patients in long-term survival, whereas no evidence of worse in-hospital mortality rate was found. Patients with mild preoperative renal insufficiency showed a higher mortality rate than other studies

Change in Functional Moderate Mitral Regurgitation after Aortic Valve Replacement

Abstract Objective: To evaluate the changes of the mitral valve geometrics and the degrees of moderate mitral regurgitation (MR) in patients undergoing aortic valve replacement (AVR) for aortic stenosis (AS). Methods: A retrospective analysis study of intraoperative transesophageal echocardiography (TEE) and postoperative transthoracic echocardiography (TTE) was performed in 49 patients diagnosed with pure AS combined with moderate MR, who underwent AVR from January 2013 to December 2017. TEE was used to evaluate the direct geometric changes of the mechanical effects on mitral annulus after AVR. TTE was used to evaluate the changes of MR after operation. All patients underwent TTE during the midterm follow-up. The mean follow-up time was 40.21 months. Results: All of the 49 patients had moderate MR. Anterolateral-posteromedial diameter, anterior-posterior diameter, and mitral annular area were significantly reduced after AVR, while no significant changes were found in the intraoperative left ventricular loading conditions before and after AVR. The degree of mitral valve regurgitation, left ventricular size, left atrial size, left ventricular end-diastolic volume, and left ventricular to aortic pressure gradient were significantly reduced before discharge, and midterm follow-up showed good results. Conclusion: This study supports the belief that aortic outflow tract obstruction and an actual mechanical compression of the anterior mitral annulus after AVR would cause reduction in MR. Ventricular remodeling would also cause reduction in MR with time going on. Patients with AS, especially young patients with moderate MR, were most likely to benefit from AVR in early time

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Pioglitazone, the widely used thiazolidinedione, is shown to be efficient in the prevention of cardiovascular complications of T2DM. In this study, we report that pioglitazone inhibits CXCR7 expression and thus blocks chemotaxis in differentiated macrophage without perturbing cell viability or macrophage differentiation. In addition, pioglitazone-mediated CXCR7 suppression and chemotaxis inhibition occur via activating peroxisome proliferator-activated receptor γ (PPARγ) but not PPARα in differentiated macrophage. More importantly, pioglitazone therapy-induced PPARγ activation suppresses CXCR7 expression in human carotid atherosclerotic lesions. Collectively, our data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ

Verification of hub genes in the expression profile of aortic dissection.

BackgroundTo assess the mRNA expression profile and explore the hub mRNAs and potential molecular mechanisms in the pathogenesis of human thoracic aortic dissection (TAD).MethodologymRNA microarray expression signatures of TAD tissues (n = 6) and non-TAD tissues (NT; n = 6) were analyzed by an Arraystar human mRNA microarray. Real-time PCR (qRT-PCR) was used to validate the results of the mRNA microarray. Bioinformatic tools, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, were utilized. Protein-protein interaction (PPI) networks were constructed based on data from the STRING database. Molecular Complex Detection (MCODE) and cytoHubba analyses were used to predict the strongest hub gene and pathway.ResultsThe top 10 hub genes were CDK1, CDC20, CCNB2, CCNB1, MAD2L1, AURKA, C3AR1, NCAPG, CXCL12 and ASPM, which were identified from the PPI network. Module analysis revealed that TAD was associated with the cell cycle, oocyte meiosis, the p53 signaling pathway, and progesterone-mediated oocyte maturation. The qRT-PCR results showed that the expression of all hub genes was significantly increased in TAD samples (p ConclusionsCDK1 could be used as a potential diagnostic biomarker and therapeutic target of TAD