Circular RNAs (circRNAs) are involved in gene regulation in a variety of physiological and pathological processes. The present study aimed to investigate the effect of circRNA_000203 on cardiac hypertrophy and the potential mechanisms involved. CircRNA_000203 was found to be up-regulated in the myocardium of Ang-II-infused mice and in the cytoplasma of Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Enforced expression of circRNA_000203 enhances cell size and expression of atrial natriuretic peptide and β-myosin heavy chain in NMVCs. In vivo, heart function was impaired and cardiac hypertrophy was aggravated in Ang-II-infused myocardium-specific circRNA_000203 transgenic mice (Tg-circ203). Mechanistically, we found that circRNA_000203 could specifically sponge miR-26b-5p, -140-3p in NMVCs. Further, dual-luciferase reporter assay showed that miR-26b-5p, -140-3p could interact with 3′-UTRs of Gata4 gene, and circRNA_000203 could block the above interactions. In addition, Gata4 expression is transcriptionally inhibited by miR-26b-5p, -140-3p mimic in NMVCs but enhanced by over-expression of circRNA_000203 in vitro and in vivo. Functionally, miR-26b-5p, -140-3p, and Gata4 siRNA, could reverse the hypertrophic growth in Ang-II-induced NMVCs, as well as eliminate the pro-hypertrophic effect of circRNA_000203 in NMVCs. Furthermore, we demonstrated that NF-κB signalling mediates the up-regulation of circRNA_000203 in NMVCs exposed to Ang-II treatment. Our data demonstrated that circRNA_000203 exacerbates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p leading to enhanced Gata4 levels.

Background: Abdominal aortic aneurysms (AAAs) can result in high mortality upon rupture but are usually undiagnosed because of the absence of symptoms in the early stage. Ultrasound screening is regarded as an impactful way to prevent the AAA-related death but cannot be performed efficiently; therefore, a target population, especially in Asia, for this procedure is lacking. Additionally, although dyslipidaemia and atherosclerosis are associated with AAA. However, it remains undetermined whether the non-high-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol ratio (NHHR) is associated with AAA. Therefore, this study was aimed at examining whether NHHR is associated with AAA. Method: A total of 9559 participants who underwent AAA screening at Guangdong Provincial People’s Hospital and through screening in two communities in Dongguan, from June 2019 to June 2021 joined in this screening program. The diagnosis of AAA was confirmed by the ultrasound examination of the abdominal aorta rather than any known or suspected AAA. Clinical and laboratory data of participants were collected. The participants were separated into a normal group and an AAA group according to the abdominal aortic status. To eliminate confounding factors, a propensity score matching (PSM) approach was utilized. The independent relationship between NHHR and AAA was assessed through the utilization of multivariable logistic regression analysis. In addition, internal consistency was evaluated through subgroup analysis, which controlled for significant risk factors. Results: Of all the participants, 219 (2.29%) participants were diagnosed with AAA. A significant elevation in NHHR was identified in the AAA group when contrasted with that in the normal group (P < 0.001). As demonstrated by the results of the multivariable logistic regression analysis, AAA was independently associated with NHHR before (odds ratio [OR], 1.440, P < 0.001) and after PSM (OR, 1.515, P < 0.001). Significant extension was observed in the areas under the receiver operating characteristic curves (AUROCs) of NHHR compared to those of single lipid parameters before and after PSM. An accordant association between NHHR and AAA in different subgroups was demonstrated by subgroup analysis. Conclusion: In the Chinese population, there is an independent association between NHHR and AAA. NHHR might be propitious to distinguish individuals with high risk of AAA.

Background: Spinal cord ischemia (SCI) is a recognized grave complication after thoracic endovascular aortic repair (TEVAR). The present study aimed to evaluate the incidence and investigate risk of SCI after TEVAR based on current prophylactic strategies designed against established risk factors. Methods: The study retrospectively reviewed a prospectively maintained database to investigate patients who underwent TEVAR successfully between January 2009 and December 2012 in a single cardiovascular center. Detailed assessment of SCI risk was routinely performed for all patients before TEVAR was carried out. Prophylactic measures, including left subclavian artery (LSA) revascularization, blood pressure augmentation and cerebrospinal fluid (CSF) pressure control after TEVAR, were employed in high-risk patients and physical neurological examinations were regularly done to evaluate SCI after TEVAR. Patients were further divided into SCI group and non-SCI group. Results: A total of 650 patients were enrolled in the study. Eleven patients (1.69%) developed SCI after TEVAR. Baseline level of hemoglobin was significantly lower in the SCI group (113.00 vs. 128.50, P=0.023). More patients in the SCI patients in the SCI group underwent TEVAR under general anesthesia (45.5% vs. 17.7%, P=0.033). A significantly higher incidence of post TEVAR hypotension was found in the SCI group (2.7% vs. 27.3%, P=0.004). Logistic regression analysis revealed that post-TEVAR hypotension (OR, 8.379; 95% CI, 1.833–38.304; P=0.006) was strongly associated with development of SCI and high normal baseline hemoglobin was a protective factor (OR, 0.969; CI, 0.942–0.998; P=0.037). The mortality in hospital and mortality at 1 year were not significant different between the SCI and the non-SCI group (0% vs. 1.6% P=1.000; 9.1% vs. 3.0%, P=0.294, respectively). While length of post-TEVAR stay (13.00 vs. 7.00 days, P=0.000) and length of hospital stay (20.00 vs. 13.00 days, P=0.001) were significantly greater in the SCI group. Conclusions: Our study revealed that, based on current prophylactic measures to curtail SCI, including LSA revascularization, blood pressure augmentation and CSF pressure control after TEVAR, post-TEVAR hypotension remains a major and independent risk factor for SCI and high normal baseline hemoglobin level is protective. SCI results in longer post-TEVAR stay and hospital stay, but not associated with increased mortality. Robust precautions should be taken against underlying causes for post-TEVAR hypotension and low level of hemoglobin should be avoided.

Development of non-surgical treatment of human abdominal aortic aneurysm (AAA) has clinical significance. Colchicine emerges as an effective therapeutic regimen in cardiovascular diseases. Yet, whether colchicine slows AAA growth remain controversy. Here, we demonstrated that daily intragastric administration of low-dose colchicine blocked AAA formation, prevented vascular smooth muscle cell (SMC) phenotype switching and apoptosis, and vascular inflammation in both peri-aortic CaPO₄ injury and subcutaneous angiotensin-II infusion induced experimental AAA mice models. Mechanistically, colchicine increased global mRNA stability by inhibiting the METTL14/YTHDC1-mediated m6A modification, resulting in increased sclerostin (SOST) expression and consequent inactivation of the WNT/β-catenin signaling pathway in vascular SMCs from mouse AAA lesions and in cultured human aortic SMCs. Moreover, human and mouse AAA lesions all showed increased m6A methylation, decreased SOST expression, and skewed synthetic SMC de-differentiation phenotype, compared to those without AAA. This study uncovers a novel mechanism of colchicine in slowing AAA development by using the METTL14/SOST/WNT/β-catenin axis to control vascular SMC homeostasis in mouse aortic vessels and in human aortic SMCs. Therefore, use of colchicine may benefit AAA patients in clinical practice.