Background
The aberrantly increased proliferation and migration of vascular smooth muscle cells (VSMCs) was critically associated with atherosclerosis (AS) progression. MiR-197-3p has been confirmed ...to regulate various biological processes, such as tumorigenesis; however, whether miR-197-3p is involved with the pathological development of AS remains largely unknown.
Methods
The serum levels of miR-197-3p in AS patients and healthy donors were determined by polymerase chain reaction (PCR) assay. The transfection efficacies of miR-197-3p mimic or inhibitor in VSMCs were evaluated by PCR assay. The effects of miR-197-3p on VSMC proliferation and migration were determined by EdU cell proliferation and Traswell migration assays. Western blotting was conducted to evaluate the effect of miR-197-3p on WDR5 expression in VSMCs.
Results
In the present study, we found that the expression of miR-197-3p was decreased in the serum of AS patients compared to healthy donors. Overexpression of miR-197-3p inhibited the proliferation and migration of VSMCs, while silencing miR-197-3p showed opposite effects. Mechanistical study revealed that WD Repeat Domain 5 (WDR5) was a target of miR-197-3p. Moreover, miR-197-3p was downregulated in VSMCs upon IL6 treatment and inhibited IL6-induced proliferation and migration in VSMCs.
Conclusions
These findings indicate that miR-197-3p could serve as a promising diagnostic marker for AS and that targeting IL6/miR-197-3p/WDR5 axis might be a potential approach to treat AS.
Introduction Intracranial atherosclerotic disease (ICAD) induces the luminal narrowing of an intracranial vessel and represents one of the major causes of ischemic strokes 1, 2, 3, 4. In vitro 3D ...printed models have gained popularity in the stroke research field as they are morphologically accurate and offer the possibility to simulate clinical scenarios for training purposes or device testing. Despite being a challenge for interventionalists, to date, clinically accurate ICAD in vitro models have not been developed. We aimed to develop a 3D printed ICAD model including realistic features to provide an optimal simulation phantom for research and training purposes. Methods Stereolithography 3D printing technique was used to create a resin neurovascular model based on vascular anatomies extracted from anonymized CTA images. The phantom includes the aortic arch, all supraoptic cervical arteries and a complete circle of Willis up to the M2‐MCA, A2‐ACA and P2‐PCA segments. 3% sodium alginate solution was cast into a stenosis mold and crosslinked in a 40% calcium chloride. The deformable gel constituted an 8mm long replaceable stenotic segment at the level of M1‐MCA simulating an atherosclerotic plaque with a 0.5mm internal diameter. A flow sensor (ME‐8PXL, Transonic) was used to measure the lesion flow rate before and after endovascular treatment was performed under fluoroscopy. Results The baseline angiographic run showed an irregular 80% stenosis at the level of M1‐MCA that generated a substantial delay of contrast arrival to the distal branches. After angioplasty (Gateway PTA Balloon Catheter 3.5x20mm, Boston Scientific) and stenting (Wingspan 2.5mmx15mm, Stryker) were performed the residual stenosis was <10% (Figure 1). An initial stenosis flow rate was registered with a value of 8.5 ± 5.33 mL/min. Following the completion of the endovascular procedure, the flow sensor detected a post‐procedural stenosis flow rate of 160 ± 3.45 mL/min. Conclusion The developed ICAD model is anatomically accurate and offers realistic physiological and procedural features. The phantom represents an ideal tool for training purposes and a platform to test different devices for the endovascular treatment of ICAD. The methodology and materials could be applied to simulate stenotic lesions at different levels in the cervical and intracranial arteries.
Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to ...being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need to reduce levels to no advice on treatment. New insight in epidemiology now suggests that these lipoproteins, marked by high triglycerides, are strong and independent predictors of ASCVD and all-cause mortality, and that their cholesterol content or remnant cholesterol likewise are strong predictors of ASCVD. Of all adults, 27% have triglycerides >2 mmol/L (176 mg/dL), and 21% have remnant cholesterol >1 mmol/L (39 mg/dL). For individuals in the general population with nonfasting triglycerides of 6.6 mmol/L (580 mg/dL) compared with individuals with levels of 0.8 mmol/L (70 mg/dL), the risks were 5.1-fold for myocardial infarction, 3.2-fold for ischemic heart disease, 3.2-fold for ischemic stroke, and 2.2-fold for all-cause mortality. Also, genetic studies using the Mendelian randomization design, an approach that minimizes problems with confounding and reverse causation, now demonstrate that triglyceride-rich lipoproteins are causally associated with ASCVD and all-cause mortality. Finally, genetic evidence also demonstrates that high concentrations of triglyceride-rich lipoproteins are causally associated with low-grade inflammation. This suggests that an important part of inflammation in atherosclerosis and ASCVD is because of triglyceride-rich lipoprotein degradation and uptake into macrophage foam cells in the arterial intima. Taken together, new insights now strongly suggest that elevated triglyceride-rich lipoproteins represent causal risk factors for low-grade inflammation, ASCVD, and all-cause mortality.
Dysfunction of the endothelial lining of lesion-prone areas of the arterial vasculature is an important contributor to the pathobiology of atherosclerotic cardiovascular disease. Endothelial cell ...dysfunction, in its broadest sense, encompasses a constellation of various nonadaptive alterations in functional phenotype, which have important implications for the regulation of hemostasis and thrombosis, local vascular tone and redox balance, and the orchestration of acute and chronic inflammatory reactions within the arterial wall. In this review, we trace the evolution of the concept of endothelial cell dysfunction, focusing on recent insights into the cellular and molecular mechanisms that underlie its pivotal roles in atherosclerotic lesion initiation and progression; explore its relationship to classic, as well as more recently defined, clinical risk factors for atherosclerotic cardiovascular disease; consider current approaches to the clinical assessment of endothelial cell dysfunction; and outline some promising new directions for its early detection and treatment.
Atherosclerosis and its attendant clinical complications, such as myocardial infarction, stroke, and peripheral artery disease, are the leading cause of morbidity and mortality in Western societies. ...In response to biochemical and biomechanical stimuli, atherosclerotic lesion formation occurs from the participation of a range of cell types, inflammatory mediators, and shear stress. Over the past decade, microRNAs (miRNAs) have emerged as evolutionarily conserved, noncoding small RNAs that serve as important regulators and fine-tuners of a range of pathophysiological cellular effects and molecular signaling pathways involved in atherosclerosis. Accumulating studies reveal the importance of miRNAs in regulating key signaling and lipid homeostasis pathways that alter the balance of atherosclerotic plaque progression and regression. In this review, we highlight current paradigms of miRNA-mediated effects in atherosclerosis progression and regression. We provide an update on the potential use of miRNAs diagnostically for detecting increasing severity of coronary disease and clinical events. Finally, we provide a perspective on therapeutic opportunities and challenges for miRNA delivery in the field.
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