Comparison of the medial midline and the anterolateral portal in ankle arthroscopy for the treatment of osteochondral lesions of the medial talus.

PURPOSE: To compare the clinical efficacy and complication rates between the medial midline and anterolateral portals in ankle arthroscopy for treating medial osteochondral lesions of the talus (OLTs). METHODS: We retrospectively analyzed patients with medial OLTs who underwent either a dual medial approach (via the medial midline and anteromedial portal) or a traditional approach (via the anterolateral and anteromedial portal) between June 2017 and January 2023. The degree of injury was evaluated by radiographs, computed tomography, and magnetic resonance imaging. Clinical outcomes were assessed using the visual analog scale (VAS), the American Orthopaedic Foot and Ankle Society (AOFAS) score, and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system. The incidence of postoperative complications, including superficial peroneal nerve (SPN) injury, was evaluated in all patients. RESULTS: There were 39 patients in total; 16 patients underwent the dual medial approach, and 23 patients underwent the traditional approach. The mean age was 39.4 ± 9.0 years, and the mean follow-up duration was 18.7 ± 6.4 months. The clinical outcomes improved significantly in both groups (*P < 0.05), but there was no significant difference between the two groups (P > 0.05). Postoperative complications were mainly SPN injury. The incidence of SPN injury was 13.0% in the traditional approach group and 0% in the dual medial approach group, with no significant difference between the two groups (P > 0.05), but a trend of reduction in SPN injury was observed in the dual medial approach group. CONCLUSION: The dual medial approach can also treat medial OLTs well, providing clear visualization and more convenient operation and reducing the possibility of injury to the SPN compared with the traditional approach. Therefore, we consider that the MM portal would be a good alternative to the anterolateral portal in treating medial OLTs.

A comparison of treatment between mini T-plate and headless cannulated compression screw in calcaneal osteotomy.

PURPOSE: In clinical studies, we discovered that when using headless cannulated compression screw fixation, many patients complain of heel pain and frequently need to have the screws removed, whereas this occurrence is uncommon with plate fixation. This study aims to compare the clinical outcome of a mini T-plate and headless cannulated compression screws in calcaneal osteotomy. METHODS: We reviewed the medical records of patients who had calcaneal osteotomy performed by one senior chief surgeon in our hospital between January 2014 and May 2021. Thirty-nine patients met the selection criteria: 22 were fixed using a mini T-plate through a modified small "L" incision on the lateral aspect of the calcaneus and 17 were fixed using double screws through an oblique incision on the lateral aspect of the calcaneus. Then, we compared the patient demographics, surgical statistics, and postoperative complications in calcaneal osteotomy between a mini T-plate and double 6.5-mm headless cannulated compressed screws. RESULTS: Each patient attained radiographic union. The average age was 49.23±13.80 (range: 24-76) years and the average follow-up duration was 47.07±8.64 (range: 36-66) weeks. The average operation duration and times of intraoperative fluoroscopy were significantly lower in the mini T-plate group (P<0.05). There was a savings of $838.88 per patient when using double screws for fixation. The incidence of hardware-related pain and implant removal was lower in the mini T-plate group (P<0.05). There is no significant difference between the two groups in terms of delayed incision healing and clinical neurological complications (P>0.05). CONCLUSIONS: In calcaneal osteotomy, the operation duration, times of intraoperative fluoroscopy, hardware-related pain, and implant removal rate were lower with mini T-plate fixation than with double screws fixation. Therefore, we consider that the mini T-plate would be a good alternative to double screws in calcaneal osteotomy.

Coronary artery segmentation in angiographic videos utilizing spatial-temporal information.

BACKGROUND: Coronary artery angiography is an indispensable assistive technique for cardiac interventional surgery. Segmentation and extraction of blood vessels from coronary angiographic images or videos are very essential prerequisites for physicians to locate, assess and diagnose the plaques and stenosis in blood vessels. METHODS: This article proposes a novel coronary artery segmentation framework that combines a three-dimensional (3D) convolutional input layer and a two-dimensional (2D) convolutional network. Instead of a single input image in the previous medical image segmentation applications, our framework accepts a sequence of coronary angiographic images as input, and outputs the clearest mask of segmentation result. The 3D input layer leverages the temporal information in the image sequence, and fuses the multiple images into more comprehensive 2D feature maps. The 2D convolutional network implements down-sampling encoders, up-sampling decoders, bottle-neck modules, and skip connections to accomplish the segmentation task. RESULTS: The spatial-temporal model of this article obtains good segmentation results despite the poor quality of coronary angiographic video sequences, and outperforms the state-of-the-art techniques. CONCLUSIONS: The results justify that making full use of the spatial and temporal information in the image sequences will promote the analysis and understanding of the images in videos.

Coronary angiography video segmentation method for assisting cardiovascular disease interventional treatment.

BACKGROUND: Coronary heart disease is one of the diseases with the highest mortality rate. Due to the important position of cardiovascular disease prevention and diagnosis in the medical field, the segmentation of cardiovascular images has gradually become a research hotspot. How to segment accurate blood vessels from coronary angiography videos to assist doctors in making accurate analysis has become the goal of our research. METHOD: Based on the U-net architecture, we use a context-based convolutional network for capturing more information of the vessel in the video. The proposed method includes three modules: the sequence encoder module, the sequence decoder module, and the sequence filter module. The high-level information of the feature is extracted in the encoder module. Multi-kernel pooling layers suitable for the extraction of blood vessels are added before the decoder module. In the filter block, we add a simple temporal filter to reducing inter-frame flickers. RESULTS: The performance comparison with other method shows that our work can achieve 0.8739 in Sen, 0.9895 in Acc. From the performance of the results, the accuracy of our method is significantly improved. The performance benefit from the algorithm architecture and our enlarged dataset. CONCLUSION: Compared with previous methods that only focus on single image analysis, our method can obtain more coronary information through image sequences. In future work, we will extend the network to 3D networks.

Overexpression of Ubiquitin-Specific Protease 2 (USP2) in the Heart Suppressed Pressure Overload-Induced Cardiac Remodeling.

Ubiquitin-specific protease 2 (USP2) is an important member of the deubiquitination system. GEO dataset revealed that USP2 was downregulated in the hearts under pressure overload. However, the cardiomyocyte-specific function of USP2 in the setting of pressure overload is unknown. In the current study, a mouse model of pressure overload was induced by transverse aortic constriction (TAC, 2 weeks). Overexpression of USP2 in the heart was conducted by AAV9 infection. Changes in heart histology were detected by Masson's trichrome staining and hematoxylin-eosin staining (H&E). Echocardiography was used to assess cardiac function. The size of cardiomyocytes was examined by wheat germ agglutinin (WGA) staining. Cardiac oxidative stress was detected by dihydroethidine staining. Our results showed that USP2 was downregulated in the cardiomyocytes following 2 weeks of TAC. Overexpression of cardiac USP2 preserved ventricular function following 2 weeks of TAC. Overexpression of cardiac USP2 inhibited TAC-induced cardiac remodeling, by suppressing cardiac hypertrophy, inhibiting inflammatory responses and fibrosis, and attenuating oxidative stress. Our findings reveal a previously unrecognized role of USP2 in regulating pressure overload-induced cardiac remodeling.

Poly(ADP-ribose) polymerase inhibition prevents reactive oxygen species induced inhibition of aldehyde dehydrogenase2 activity.

Lipid peroxidation plays a critical role in cardiovascular diseases. Aldehydes are the major end products of lipid peroxidation and can be metabolized into less reactive chemical species by aldehyde dehydrogenase 2 (ALDH2). However, ALDH2 dehydrogenase activity can be affected by many factors including reactive oxygen species. To elucidate how reactive oxygen species inhibit ALDH2 dehydrogenase activity, we stimulated human aortic endothelial cells (HAECs) with oxidized low-density lipoproteins (ox-LDL) and performed a myocardial ischemia-reperfusion model. Ox-LDL treatment and ischemia-reperfusion injury inhibited ALDH2 dehydrogenase activity. Poly(ADP-ribose) polymerase (PARP) was activated by ox-LDL stimulation and ischemia-reperfusion injury and PARP inhibition partly restored ALDH2 dehydrogenase activity in ox-LDL treated HAECs and ischemia-reperfusion rat hearts. SIRT3 was upregulated by ox-LDL stimulation and ischemia-reperfusion injury and downregulated by PARP inhibition. Using siRNA to knock down SIRT3, we demonstrated that SIRT3 mediated deacetylation decreased ALDH2 dehydrogenase activity and PARP inhibition partly restored ALDH2 dehydrogenase activity through preventing SIRT3 expression and subsequently preserving ALDH2 acetylation.

IL-38 attenuates myocardial ischemia-reperfusion injury by inhibiting macrophage inflammation.

BACKGROUND: Reperfusion therapy is the most effective approach to resolve coronary occlusion, but myocardial injury caused by excessive inflammation during myocardial ischemia-reperfusion will also pose a new threat to health. Our prior study revealed the expression pattern of interleukin-38 (IL-38) in the peripheral blood serum of patients with ischemic cardiomyopathy and the role of IL-38 in acute myocardial infarction in mice. However, its role and potential mechanisms in myocardial ischemia/reperfusion injury (MIRI) remain to be determined. METHODS AND RESULTS: The left anterior descending artery of C57BL/6 mice was transiently ligated to induce the MIRI model. We found that MIRI induced the expression of endogenous IL-38, which was mainly produced by locally infiltrating macrophages. Overexpression of IL-38 in C57BL/6 mice attenuated inflammatory injury and decreased myocardial apoptosis after myocardial ischemia-reperfusion. Furthermore, IL-38 inhibited lipopolysaccharide-induced macrophage inflammation in vitro. Cardiomyocytes cocultured with the supernatant of IL-38- and troponin I-treated macrophages showed a lower rate of apoptosis than controls. CONCLUSIONS: IL-38 attenuates MIRI by inhibiting macrophage inflammation. This inhibitory effect may be partially achieved by inhibiting the activation of NOD-like receptor pyrin domain-related protein 3 inflammasome, resulting in decreased expression of inflammatory factors and reduced cardiomyocyte apoptosis.

Experimental study on repair of cartilage defects in the rabbits with GelMA-MSCs scaffold prepared by three-dimensional bioprinting.

Cartilage damage is a common orthopedic disease, which can be caused by sports injury, obesity, joint wear, and aging, and cannot be repaired by itself. Surgical autologous osteochondral grafting is often required in deep osteochondral lesions to avoid the later progression of osteoarthritis. In this study, we fabricated a gelatin methacryloyl-marrow mesenchymal stem cells (GelMA-MSCs) scaffold by three-dimensional (3D) bioprinting. This bioink is capable of fast gel photocuring and spontaneous covalent cross-linking, which can maintain high viability of MSCs and provide a benign microenvironment to promote the interaction, migration, and proliferation of cells. In vivo experiments, further, proved that the 3D bioprinting scaffold can promote the regeneration of cartilage collagen fibers and have a remarkable effect on cartilage repair of rabbit cartilage injury model, which may represent a general and versatile strategy for precise engineering of cartilage regeneration system.

Generation of a human iPSC line ZZUNEUi014-A from a patient with antithrombin deficiency caused by mutation in SERPINC1 gene.

Inherited antithrombin (AT) deficiency is an autosomal dominant disorder associated with SERPINC1 mutations. In this study, we generated a human induced pluripotent stem cell (iPSC) line ZZUNEUi014-A from peripheral blood mononuclear cells of a female AT deficiency patient with the p. W27X (c. 80G > A) mutation in SERPINC1. This cell line expressed pluripotency markers, showed normal female karyotype and could differentiate into all three germ layers in vitro.

Safety and Efficacy of Drug-Coated Balloons in Patients with Acute Coronary Syndromes and Vulnerable Plaque.

BACKGROUND: Percutaneous coronary intervention (PCI) is the main treatment option for acute coronary syndromes (ACS) often related to the progression and rupture of vulnerable plaques. While drug-eluting stents (DES) are now routinely used in PCI, drug-coated balloons (DCB) are a new strategy to PCI and their practice in the treatment of ACS with vulnerable plaques has not been reported. This study aimed to evaluate the safety and efficacy of DCB in ACS complicated with vulnerable plaque lesions. METHODS: 123 patients were retrospectively analyzed and diagnosed with ACS and given PCI in our Cardiology Department from December 2020 to July 2022. Vulnerable plaques were confirmed by intravenous ultrasound (IVUS) in all patients. According to individual treatment plan, patients were entered into either DCB (n = 55) or DES (n = 68) groups. The results of coronary angiography and IVUS before and immediately after percutaneous coronary intervention were analyzed. The occurrence of major adverse cardiovascular events (MACE) and the results of coronary angiography were also evaluated during follow-up. RESULTS: There were no significant differences in baseline clinical characteristics, preoperative minimal luminal diameter (MLD), and preoperative diameter stenosis (DS) between the two groups. Also, there were no differences in IVUS plaque burden (PB), vessel area, and lumen area in the two groups before and immediately after PCI. The efficacy analysis showed that immediately after PCI, the DCB group had smaller MLD and higher degrees of lumen stenosis than the DES group (P < 0.05). However, during follow-up, no significant differences in MLD and DS were seen in two groups; relatively, late loss in luminal diameter（LLL）in the DCB group was smaller (P＜0.05). Safety analysis showed that during follow-up, 9 patients developed restenosis after DCB implantation while restenosis occurred in 10 patients with DES treatment, no statistical difference in the incidence of restenosis in the two groups. Besides, there was no statistical difference in the incidence of major adverse cardiac events（MACE）during hospitalization and follow-up in the DCB group (7.3% (4/55)) and the DES group (8.8% (6/68)). CONCLUSION: DCB is safe and effective for ACS complicated with vulnerable plaque and has an advantage over DES in LLL.

Optical flow estimation of coronary angiography sequences based on semi-supervised learning.

Optical flow is widely used in medical image processing, such as image registration, segmentation, 3D reconstruction, and temporal super-resolution. However, high-precision optical flow training datasets for medical images are challenging to produce. The current optical flow estimation models trained on these non-medical datasets, such as KITTI, Sintel, and FlyingChairs are unsuitable for medical images. In this work, we propose a semi-supervised learning mechanism to estimate the optical flow of coronary angiography. Our proposed method only needs the original medical images, segmentation results of regions of interest, and pre-trained models based on other optical flow datasets to train a new optical flow estimation model suitable for medical images. First, we use the coronary segmentation results to perform image enhancement processing on the coronary vascular region to improve the image contrast between the vascular region and the surrounding tissues. Then, we extract the high-precision optical flow of coronary arteries based on the coronary-enhanced images and the pre-trained optical flow estimation model. After estimating the optical flow, we take it and its corresponding original coronary angiography images as the training dataset to train the optical flow estimation network. Furthermore, we generate a large-scale synthetic Flying-artery dataset based on coronary artery segmentation results and original coronary angiography images, which is used to improve and evaluate the accuracy of optical flow estimation for coronary angiography. The experimental results on the coronary angiography datasets demonstrate that our proposed method can significantly improve the optical flow estimation accuracy of coronary angiography sequences compared with other methods.

Analysis of the Correlation Between the Ratio of Monocytes to High-Density Lipoprotein Cholesterol and in-Stent Restenosis in Patients with Premature Coronary Heart Disease.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) and monocytes are associated with coronary artery disease, and the ratio of monocytes to high-density lipoprotein (MHR) is associated with long-term adverse outcomes and the recurrence of atrial fibrillation. Currently, the trend of coronary heart disease proned to young people is becoming prominent. However, the relationship between MHR and in-stent restenosis (ISR) in patients with premature coronary heart disease (PCHD) has not been investigated. Therefore, we aimed to assess the relationship between MHR and ISR in patients with PCHD. METHODS: We retrospectively included 257 patients (men ≤ 55 years old, women ≤ 65 years old) with PCHD who underwent drug-eluting stent implantation and follow-up coronary angiography at the First Affiliated Hospital of Zhengzhou University from September 2016 to September 2019. Patients were divided into ISR and non-ISR groups depending on their follow-up coronary angiography results. Relative clinical information was recorded and analyzed. A receiver operating characteristic curve analysis was used to determine the optimum pre-procedural MHR cutoff value to predict ISR. RESULTS: Logistic regression analysis showed that MHR, smoking history, and fibrinogen were independent risk factors for ISR in patients with PCHD. The area under the receiver operating characteristic curve (AUC) of MHR was 0.750 (95% confidence interval, 0.695-0.820; P < .001), the cutoff value was 546.88, and the specificity and sensitivity were 65.2% and 78%, while the AUC of monocytes was 0.631 (95% confidence interval, 0.638-0.794; P < .001), the cutoff value was 590, and the specificity and sensitivity were 77.1% and 60.0%. CONCLUSION: MHR is an independent risk factor for ISR in patients with PCHD and showed a certain predictive value.

Saccharides from Arctium lappa L. root reduce platelet activation and thrombus formation in a laser injury thrombosis mouse model.

Arctium lappa L., also known as burdock, is a popular medicinal plant in traditional Chinese medicine due to its potential therapeutic properties. Saccharides from Arctium lappa L. root (ALR-S) have been extensively studied for their anti-inflammatory and anti-diabetes effects. Platelets play a pivotal role in thrombosis. The present study describes the effects of ALR-S on platelet activation and thrombosis using a laser injury thrombosis in vivo model. The study also measured the effects of ALR-S on platelet activation by analysing aggregation, ATP release, platelet spreading, adhesion and clot retraction in vitro. Specifically, the effects were ALR-S concentration-dependent inhibition of platelet aggregation and ATP release. Activated platelets pretreated with ALR-S showed diminished CD62P expression levels and fibrinogen binding, as measured by flow cytometry. ALR-S inhibited platelet spreading on fibrinogen and adhesion on collagen under shear. ALR-S attenuated platelet activation by decreasing oxidative stress and thrombus formation. These results demonstrated the antiplatelet effects of ALR-S, suggesting the antithrombotic and cardiovascular protective activities of ALR-S as a functional food.

The Drug Coated Balloon-Only Strategy for Treatment of de Novo Left Main Coronary Artery Bifurcation Lesion: Stentless Strategy.

The study aimed to evaluate the efficacy and safety of drug coated balloon-only strategy (DCB-only) in the treatment of de novo left main coronary artery (LM) bifurcation lesions. 85 patients were enrolled in this study and classified them into two groups: DCB-only group (n = 36) and DES group (n = 49). The MLD of target vessels was measured before and immediately after percutaneous coronary intervention (PCI) and late luminal loss (LLL) were also calculated. And the occurrence of major adverse cardiovascular events (MACE) was also evaluated. Compared with that before PCI, the MLD of target lesions significantly increased immediately after PCI (P < .05) and no MACE was recorded during the perioperative period both in two groups. The MLD at follow-up was significantly higher than that before both DCB and DES treatment. Compared with the DES group, the MLD of the DCB group was smaller than immediately after PCI in the LM and LAD (P < .05). The LLL of LAD in DCB group was smaller than that in DES group (P < .05). There was no significant difference in the incidence of luminal restenosis at the target lesion between the two groups, and no significant difference in the incidence of MACE (P > .05). The use of DCB-only to treat de novo LM bifurcation lesions is effective and relatively safe, which provides new ideas for the treatment of LM coronary artery bifurcation lesions in the future.

Asiatic acid alleviates Ang-II induced cardiac hypertrophy and fibrosis via miR-126/PIK3R2 signaling.

BACKGROUND: Cardiac hypertrophy is an independent risk factor of many cardiovascular diseases. Studies have demonstrated that microRNA-126 (miR-126) was involved in angiogenesis during physiological and pathological process. However, its role in cardiac hypertrophy has not been known clearly. Our previous study demonstrated that asiatic acid (AA) has obvious protective effect on cardiac hypertrophy. Here, this study aimed to discover the regulatory role of miR-126 and its mechanism in cardiac hypertrophy, and to determine whether AA's anti-hypertrophy effect is partially miR-126 dependent. METHODS: Male Sprague Dawley rats were AngII infused via osmotic minipumps for 4 weeks and were treated with AA (20 mg/kg/day) by oral gavage. Cardiac hypertrophy was assessed using the echocardiography and histological analysis. In vitro studies,cardiomyocyte and cardiac fibroblasts (CF) were treted with AngII and AngII plus AA. And, the effect of AA on miR-126 and PI3K/AKT signaling pathway was investigated. RESULTS: Treatment of rats with AA decreased the ratio of heart weight to tibia length and hypertrophy markers. In vitro exprements demonstrated that AA significantly attenuated AngII-induced cardiac growth and cardiac fibroblast collagen expression. Moreover, our results found downregulation of miR-126 and activation of PI3K/AKT signaling pathway in AngII infusion induced cardiac hypertrophy model. It was also determined that miR-126 targets PIK3R2 directly. CONCLUSIONS: AA supplementation upregulated the expression of miR-126 and conferred cardio-protection effect against AngII induced cardiac hypertrophy.

Protection against Doxorubicin-Related Cardiotoxicity by Jaceosidin Involves the Sirt1 Signaling Pathway.

The clinical use of doxorubicin (DOX) is largely limited by its cardiotoxicity. Previous studies have shown that jaceosidin has many biological activities. However, little is known about whether jaceosidin can attenuate DOX-related acute cardiotoxicity. Here, we investigated the therapeutic effects of jaceosidin on DOX-induced acute cardiotoxicity. Mice were intraperitoneally injected with a single dose of DOX to establish an acute cardiac injury model. To explore the protective effects, mice were orally administered jaceosidin daily for 7 days, with dosing beginning 2 days before DOX injection. The results demonstrated that jaceosidin dose-dependently reduced free radical generation, inflammation accumulation, and cell loss induced by DOX in cardiomyocytes. Further studies showed that jaceosidin treatment inhibited myocardial oxidative damage and the inflammatory response and attenuated myocardial apoptotic death, thus improving cardiac function in mice injected with DOX. The inhibitory effects of jaceosidin on DOX-related acute cardiotoxicity were mediated by activation of the sirtuin1 (Sirt1) signaling pathway. Jaceosidin lost its protective effect against DOX-related injury in Sirt1-deficient cardiomyocytes and mice. In conclusion, jaceosidin has protective potential in treating DOX-related cardiac injury through activation of the Sirt1 signaling pathway.

Deletion of Seipin Attenuates Vascular Function and the Anticontractile Effect of Perivascular Adipose Tissue.

Seipin locates in endoplasmic reticulum (ER) and regulates adipogenesis and lipid droplet formation. Deletion of Seipin has been well-demonstrated to cause severe general lipodystrophy, however, its role in maintaining perivascular adipose tissue (PVAT) and vascular homeostasis has not been directly assessed. In the present study, we investigated the role of Seipin in mediating the anticontractile effect of PVAT and vascular function. Seipin expression in PVAT and associated vessels were detected by qPCR and western-blot. Seipin is highly expressed in PVAT, but hardly in vessels. Structural and functional alterations of PVAT and associated vessels were compared between Seipin -/- mice and WT mice. In Seipin -/- mice, aortic and mesenteric PVAT were significantly reduced in mass and adipose-derived relaxing factors (ADRFs) secretion, but increased in macrophage infiltration and ER stress, as compared with those in WT mice. Aortic and mesenteric artery rings from WT and Seipin -/- mice were mounted on a wire myograph. Vasoconstriction and vasodilation were studied in vessels with and without PVAT. WT PVAT augmented relaxation but not Seipin -/- PVAT, which suggest impaired anticontractile function in PVAT of Seipin -/- mice. Thoracic aorta and mesenteric artery from Seipin -/- mice had impaired contractility in response to phenylephrine (PHE) and relaxation to acetylcholine (Ach). In conclusion, Seipin deficiency caused abnormalities in PVAT morphology and vascular functions. Our data demonstrated for the first time that Seipin plays a critical role in maintaining PVAT function and vascular homeostasis.

Inhibition of long noncoding RNA HIF1A-AS2 confers protection against atherosclerosis via ATF2 downregulation.

INTRODUCTION: In atherosclerotic lesions, extensive inflammation of the vessel wall contributes to plaque instability. Long noncoding RNAs (lncRNAs) play important roles in diverse biological processes in atherosclerosis. OBJECTIVES: Here, we aim to identify the functional role and regulatory mechanisms of lncRNA hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2) in atherosclerotic inflammation. METHODS: An atherosclerotic mouse model was induced in ApoE-/- mice by high fat diet (HFD). Endothelial cells (ECs), human aortic smooth muscle cells (SMCs) or human coronary artery endothelial cells (HCAECs) were exposed to ox-LDL to develop the in vitro model. The effects of lncRNA HIF1A-AS2 on inflammation were evaluated by determining levels of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and levels of adhesion molecules vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and macrophage cationic peptide 1 (MCP-1). RESULTS: It was established that lncRNA HIF1A-AS2 and ATF2 were highly expressed in atherosclerotic ApoE-/- mice. Downregulating lncRNA HIF1A-AS2 in ox-LDL-exposed ECs, SMCs and HCAECs inhibited inflammation by reducing levels of pro-inflammatory factors and adhesion molecules. LncRNA HIF1A-AS2 bound to the transcription factor USF1 to elevate ATF2 expression. USF1 overexpression counteracted the suppressive effect of lncRNA HIF1A-AS2 silencing on ox-LDL-induced inflammation. Knockdown of lncRNA HIF1A-AS2 or ATF2 could also attenuate inflammation in atherosclerotic mice. Collectively, the present study demonstrates that downregulation of lncRNA HIF1A-AS2 represses the binding of USF1 to the ATF2 promoter region and then inhibits ATF2 expression, thereby suppressing atherosclerotic inflammation. CONCLUSION: This study suggests lncRNA HIF1A-AS2 as an promising therapeutic target for atherosclerosis.

The protective role of DPP4 inhibitors in atherosclerosis.

Diabetes is a chronic non-communicable disease whose incidence continues to grow rapidly, and it is one of the most serious and critical public health problems. Diabetes complications, especially atherosclerosis-related chronic vascular complications, are a serious threat to human life and health. Growing evidence suggests that dipeptidyl peptidase 4 (DPP4) inhibitors, beyond their role in improving glycemic control, are helpful in ameliorating endothelial dysfunction in humans and animal models of T2DM. In fact, DPP4 inhibitors have been shown by successive studies to play a protective effect against vascular complications. On one hand, in addition to their hypoglycemic effects, DPP4 inhibitors participate in the control of atherosclerotic risk factors by regulating blood lipids and lowering blood pressure. On the other hand, DPP4 inhibitors exert anti-atherosclerotic effects directly through multiple mechanisms, including improving endothelial cell dysfunction, increasing circulating endothelial progenitor cell (EPCs) levels, regulating mononuclear macrophages and smooth muscle cells, inhibiting inflammation and oxidative stress and improving plaque instability. Herein, we review the beneficial roles of DPP4 inhibitors in atherosclerosis as detailed.

Myricetin ameliorates atherosclerosis in the low-density-lipoprotein receptor knockout mice by suppression of cholesterol accumulation in macrophage foam cells.

BACKGROUND: Myricetin, a major flavonoid found in several foods including berries, grapes and wine, exhibited strong antioxidant potency, yet the effect on atherosclerosis is not fully understood. In this study, we examined the effect of myricetin on lipid accumulation in macrophage and atherosclerosis in atherosclerosis-prone low density lipoprotein receptor-deficient (Ldlr -/- ) mice. METHODS: Ldlr -/- mice were fed an atherogenic diet supplemented with myricetin (0.15% in the diet, v/v) for 8 weeks. Body weight, adipose tissue weight, food intake, serum biochemical parameters were measured. Atherosclerosis lesions and macrophages accumulaton in lesions were analyzed and quantified. Macrophages were exposed to 20 µM of myricetin before incubated with oxidized low-density lipoprotein (ox-LDL) (25µg/mL) or Dil-ox-LDL for the indicated time. Lipid uptake and foam cell formation were evaluated by flow cytometry and microscopy. The intracellular lipids were extracted and measured. mRNA expression and protein of cholesterol metabolism related receptors were analyzed. RESULTS: Myricetin administration reduced the weight, plasma lipid levels but not food intake in Ldlr -/- mice when fed an atherogenic diet. Myceritin-treated Ldlr -/- mice displayed significantly less atherosclerotic areas and macrophages in the cross sections of the aortic root. There were also less lipophilic areas in En face Oil red O staining of aorta from myceritin-treated Ldlr -/- mice. Myceritin treatment also markedly ameliorated ox-LDL-induced cholesterol accumulation in macrophages. The expression of CD36 were decreased in myricetin treated macrophages with ox-LDL incubation, while scavenger receptors class A (SR-A) and scavenger receptors class B (SR-BI) expression was not altered, indicating that these effect of myricetin were dependent on CD36 pathway. CONCLUSIONS: Our findings indicated that myricetin suppressed cholesterol accumulation in macrophage foam cells by inhibition of CD36-mediated ox-LDL uptake, and suggested myricetin may have an important therapeutic function for atherosclerosis.