Silencing of Long Noncoding RNA TUG1 Ameliorates Atherosclerosis-Induced Myocardial Injury by Upregulating microRNA-30b-3p and Downregulating Brd4.

ABSTRACT: Long noncoding RNAs and microRNAs (miRNAs) are emerging biomarkers involved in human diseases, and we focused on the roles of long noncoding RNA taurine upregulated gene 1 (TUG1) and miR-30b-3p in the related mechanisms of atherosclerosis-induced myocardial injury. ApoE-deficient mice were fed with high-fat diet to establish atherosclerotic models and then were subjected to either TUG1 downregulation or miR-30b-3p upregulation treatment. The serum myocardial enzymes, inflammatory biomarkers, pathological changes, intramyocardial macrophage infiltration, and apoptosis of cardiomyocytes in atherosclerotic mice were determined. The expression of TUG1, miR-30b-3p, and bromodomain protein 4 (Brd4) in atherosclerotic models was evaluated. Moreover, the correlations of TUG1, miR-30b-3p, and Brd4 were verified. TUG1 and Brd4 were increased while miR-30b-3p was decreased in atherosclerotic mice. The silenced TUG1 or elevated miR-30b-3p attenuated atherosclerosis-induced myocardial injury mainly by reducing serum myocardial enzyme content and inflammatory response, improving pathological changes, and preventing macrophage infiltration and cardiomyocyte apoptosis in atherosclerotic mice. Mechanistically, TUG1 could competitively bind with miR-30b-3p to prevent the degradation of its target gene Brd4. This study reveals that the silencing of TUG1 ameliorates atherosclerosis-induced myocardial injury by upregulating miR-30b-3p and downregulating Brd4, which may provide novel targets for atherosclerosis treatment.

Intravenous regular insulin is an efficient and safe procedure for obtaining high-quality cardiac 18F-FDG PET images: an open-label, single-center, randomized controlled prospective trial.

BACKGROUND: An open-label, single-center, randomized controlled prospective trial was performed to assess the efficiency and safety of an insulin loading procedure to obtain high-quality cardiac 18F-FDG PET/CT images for patients with coronary artery disease (CAD). METHODS: Between November 22, 2018 and August 15, 2019, 60 patients with CAD scheduled for cardiac 18F-FDG PET/CT imaging in our department were randomly allocated in a 1:1 ratio to receive an insulin or standardized glucose loading procedure for cardiac 18F-FDG imaging. The primary outcome was the ratio of interpretable images (high-quality images defined as myocardium-to-liver ratios ≥ 1). The secondary outcome was the patient preparation time (time interval between administration of insulin/glucose and 18F-FDG injection). Hypoglycemia events were recorded. RESULTS: The ratio of interpretable cardiac PET images in the insulin loading group surpassed the glucose loading group (30/30 vs. 25/30, P = 0.026). Preparation time was 71±2 min shorter for the insulin loading group than for the glucose loading group (P < 0.01). Two and six hypoglycemia cases occurred in the insulin and glucose loading groups, respectively. CONCLUSION: The insulin loading protocol was a quicker, more efficient, and safer preparation for gaining high-quality cardiac 18F-FDG images.

Intravenous insulin injection supplemented with subsequent milk consumption is a safer formulation for cardiac viability 18F-FDG imaging.

BACKGROUND: The safety and efficacy of intravenous insulin injection coupled with subsequent milk consumption was evaluated for high-quality cardiac viability F-18-fluorodeoxyglucose (18F-FDG) images. METHODS AND RESULTS: A total of 328 patients with known/suspected coronary artery disease received intravenous insulin injection with or without subsequent milk consumption for cardiac 18F-FDG imaging. When blood glucose levels had decreased by ≥ 20%, 18F-FDG was injected. Patients were scored for hypoglycemic symptoms using a 10-point scale (discomfort: 0, none; 1 to 3, mild; 4 to 6, moderate; 7 to 9, severe). An insulin-related hypoglycemic event was defined as an increased symptomatic score following insulin injection. The number of hypoglycemic events was significantly lower in the milk consumption group than in the group that did not (24/164 vs. 51/164, P < .01). Maximal and averaged standardized uptake value of the left ventricular myocardium (MyoSUVmax and MyoSUVmean) were also measured. The milk and control groups had similar mean hypoglycemic symptom scores (4.2 ± 4.0 vs. 3.3 ± 3.1, respectively), MyoSUVmax, and MyoSUVmean (11.1 ± 4.8, 7.3 ± 3.2 vs. 11.4 ± 4.5, 7.4 ± 3.2, respectively). CONCLUSION: Intravenous insulin injection supplemented with subsequent milk consumption is a safer formulation for cardiac viability 18F-FDG imaging without impairing image quality.

Astragaloside IV inhibits Angiotensin II-stimulated proliferation of rat vascular smooth muscle cells via the regulation of CDK2 activity.

AIMS: Astragaloside IV (AS-IV) is the central active component extracted from Radix astragali, an herbal remedy widely used in traditional Chinese medicine for the treatment of cardiovascular diseases. Aberrant proliferation of vascular smooth muscle cells (VSMCs) is closely involved in the initiation and progression of cardiovascular complications, such as atherosclerosis. Here we investigated whether AS-IV inhibited agonist-induced vascular smooth muscle cells (VSMCs) proliferation and the underlying mechanism. MAIN METHODS: Quiescent cultured A10 cells (adult rat VSMCs) were treated with Angiotensin II (AngII) or AngII plus AS-IV for 48 h. The growth rate of A10 cells was analyzed by CCK8 assay. RT-PCR analysis was carried out to examine the expression of α-smooth muscle actin (α-SMA), an important phenotypic modulation marker. In addition, whether the interference of AS-IV on AngII-mediated growth of VSMCs via regulation of cell cycle was evaluated by flow cytometry. In order to explore the role of cell cycle machinery, we measured kinase activity of CDK2 by Kinase assay and the protein level of Cdc25 by western blot, respectively. KEY FINDINGS: These data suggested that AS-IV exerted beneficial effects on AngII -induced abnormal growth in rat VSMCs through disturbing cell cycle, especially block G1/S transition by attenuating CDK2 activity, which may hinder the process of pathological vascular remodeling during atherosclerosis.