Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production

Sniffing out atherosclerosis Olfactory receptors are best known for their presence in the nose and their role in detecting smells, but they are also present in other tissues and perform additional biological functions. For example, vascular macrophages involved in the pathogenesis of atherosclerosis express multiple subtypes of olfactory receptors. Orecchioni et al . focused on olfactory receptor 2, a receptor for the compound octanal, and identified its contribution to atherosclerosis pathogenesis and the formation of atherosclerotic plaques (see the Perspective by Rayner and Rasheed). The authors show that most of the octanal was not directly derived from the diet, but rather was generated as a by-product of lipid peroxidation, suggesting a potential pathway for intervention. —YN

Blood microflora of patients with atherosclerotic vascular lesions and microflora of atherosclerotic plaques of carotid arteries

Aim of the study was to assess the frequency of microflora detection in the blood of patients with atherosclerotic vascular lesions and middle-aged patients without clinical symptoms of atherosclerosis. Compare the nature of microflora isolated from blood and the range of microorganisms isolated from atherosclerotic plaques (AP) of patients with carotid arteries atherosclerosis. Material and methods. The hemocultures of 118 men and 33 women with atherosclerosis (mean age 55.6 years) as well as 10 blood samples of 3 men and 7 women formed into a control group (mean age 37 years) were examined. Test samples were cultivated for 6 months. Tissue platings of carotid arteries AP in 11 women and 24 men of the main group (mean age 58.0) were incubated for 2 months. Methods based on Student’s t-test and Mann-Whitney U-test were used for statistical analysis of the obtained results. Results. Propionibacterium acnes hemocultures were detected in 9.9 % of patients from the main and control groups. In blood Staphylococcus epidermidis and Stenotrophomonas maltophylia were detected in 0.7 % of samples. P. acnes and Staphylococcus spp. cultures were obtained from AP in 34.3 and 45.7 %, including both microorganisms in 8.6 % of samples. Conclusions. P. acnes cultures are found equally frequently in the blood of atherosclerotic patients and patients not yet diagnosed with atherosclerosis. This study confirmed the presence of the same-name microorganisms in blood and atherosclerotic plaques. In 5.7 % (2 of 35) it was possible to extract simultaneously a P. acnes culture from two loci (atherosclerotic tissue and blood) in specific individuals. Further detailed research is required to study the etiological significance of the microbial factor in the atherosclerotic plaque formation.

Prediction of Mechanosensitive Genes in Vascular Endothelial Cells Under High Wall Shear Stress

Objective: The vulnerability of atherosclerotic plaques is among the leading cause of ischemic stroke. High wall shear stress (WSS) promotes the instability of atherosclerotic plaques by directly imparting mechanical stimuli, but the specific mechanisms remain unclear. We speculate that modulation of mechanosensitive genes may play a vital role in accelerating the development of plaques. The purpose of this study was to find mechanosensitive genes in vascular endothelial cells (ECs) through combining microarray data with bioinformatics technology and further explore the underlying dynamics–related mechanisms that cause the progression and destabilization of atherosclerotic plaques.Methods: Microarray data sets for human vascular ECs under high and normal WSS were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified through the R language. The performance of enrichment analysis and protein–protein interaction (PPI) network presented the biological function and signaling pathways of the DEGs. Hub genes were identified based on the PPI network and validated by GEO data sets. Predicted transcription factor (TF) genes and miRNAs interaction with potential mechanosensitive genes were identified by NetworkAnalyst.Results: A total of 260 DEGs, 121 upregulated and 139 downregulated genes, were screened between high and normal WSS from GSE23289. A total of 10 hub genes and four cluster modules were filtered out based on the PPI network. The enrichment analysis showed that the biological functions of the hub genes were mainly involved in responses to unfolded protein and topologically incorrect protein, and t to endoplasmic reticulum stress. The significant pathways associated with the hub genes were those of protein processing in the endoplasmic reticulum, antigen processing, and presentation. Three out of the 10 hub genes, namely, activated transcription factor 3 (ATF3), heat shock protein family A (Hsp70) member 6 (HSPA6), and dual specificity phosphatase 1 (DUSP1, also known as CL100, HVH1, MKP-1, PTPN10), were verified in GSE13712. The expression of DUSP1 was higher in the senescent cell under high WSS than that of the young cell. The TF–miRNA–mechanosensitive gene coregulatory network was constructed.Conclusion: In this work, we identified three hub genes, ATF3, HSPA6, and DUSP1, as the potential mechanosensitive genes in the human blood vessels. DUSP1 was confirmed to be associated with the senescence of vascular ECs. Therefore, these three mechanosensitive genes may have emerged as potential novel targets for the prediction and prevention of ischemic stroke. Furthermore, the TF–miRNA–mechanosensitive genes coregulatory network reveals an underlying regulatory mechanism and the pathways to control disease progression.

Where the Action Is—Leukocyte Recruitment in Atherosclerosis

Atherosclerosis is the leading cause of death worldwide and leukocyte recruitment is a key element of this phenomenon, thus allowing immune cells to enter the arterial wall. There, in concert with accumulating lipids, the invading leukocytes trigger a plethora of inflammatory responses which promote the influx of additional leukocytes and lead to the continued growth of atherosclerotic plaques. The recruitment process follows a precise scheme of tethering, rolling, firm arrest, crawling and transmigration and involves multiple cellular and subcellular players. This review aims to provide a comprehensive up-to-date insight into the process of leukocyte recruitment relevant to atherosclerosis, each from the perspective of endothelial cells, monocytes and macrophages, neutrophils, T lymphocytes and platelets. In addition, therapeutic options targeting leukocyte recruitment into atherosclerotic lesions—or potentially arising from the growing body of insights into its precise mechanisms—are highlighted.

The Function, Regulation and Mechanism of Programmed Cell Death of Macrophages in Atherosclerosis

Atherosclerosis is a chronic progressive inflammatory vascular disease, which is an important pathological basis for inducing a variety of cardio-cerebrovascular diseases. As a kind of inflammatory cells, macrophages are the most abundant immune cells in atherosclerotic plaques and participate in the whole process of atherosclerosis and are the most abundant immune cells in atherosclerotic plaques. Recent studies have shown that programmed cell death plays a critical role in the progression of many diseases. At present, it is generally believed that the programmed death of macrophages can affect the development and stability of atherosclerotic vulnerable plaques, and the intervention of macrophage death may become the target of atherosclerotic therapy. This article reviews the role of macrophage programmed cell death in the progression of atherosclerosis and the latest therapeutic strategies targeting macrophage death within plaques.

Ferulic Acid Alleviates Atherosclerotic Plaques by Inhibiting VSMC Proliferation Through the NO/p21 Signaling pathway

The benefits and risks of inhibiting the proliferation and migration of vascular smooth muscle cells (VSMCs) in atherosclerosis (AS) remain a subject of debate. In this study, we investigated the effect of ferulic acid (FA) on the proliferation and migration of VSMCs induced by platelet-derived growth factor (PDGF) and the associated mechanism and used ApoE-/- mice to study whether the effect of FA on VSMC proliferation and migration is beneficial in alleviating AS plaques. It was found that FA not only reduced blood lipid levels but also promoted the production of nitric oxide (NO) by MOVAS cells through the endothelial nitric oxide synthase (eNOS) pathway, inhibited the migration and proliferation of VSMCs induced by PDGF, promoted the expression of p21 in VSMCs, and exerted a therapeutic effect against AS.

Optimized Reconstruction Algorithm-Processed CT Image in the Diagnosis of Correlation between Epicardial Fat Volume and Coronary Heart Disease

This study was to analyze the application value of a reconstruction algorithm in CT images of patients with coronary heart disease and analyze the correlation between epicardial fat volume and coronary heart disease. An optimized reconstruction algorithm was constructed based on compressed sensing theory in this study. Then, the optimized algorithm was applied to the image reconstruction of multislice spiral CT image data after testing its sensitivity, accuracy, and specificity. 60 patients with suspected angina pectoris were divided into lesion group (40 cases) and normal group (20 cases) according to whether there were coronary atherosclerotic plaques in cardiac vessels. The results showed that the sensitivity, specificity, and accuracy of the optimized reconstruction algorithm were 91.78%, 84.27%, and 95.32%, and the running time was (12.18 ± 2.49) s. The CT value of the liver and the CT ratio of the liver and spleen in the lesion group were (53.81 ± 5.91) and (3.88 ± 0.67), respectively. There was no significant difference between the two groups ( P > 0.05 ). The body mass index and epicardial fat volume in the lesion group were (31.93 ± 4.54) kg/m2 and (120.09 ± 22.01) cm3, respectively. The body mass index and fat volume in the lesion group were significantly higher than those in the normal group ( P < 0.05 ). The epicardial fat constitution increased with the increase of the number of coronary arteries involved, and there was a positive correlation between them. Among patients with different coronary atherosclerotic plaques, the epicardial fat volume in patients with mixed plaques was the largest ( P < 0.05 ). In summary, optimizing CT images under compressed a sensing reconstruction algorithm could effectively improve the diagnostic accuracy of doctors. Epicardial fat volume was positively correlated with coronary heart disease. Epicardial fat volume could be used as one of the important indexes to predict coronary heart disease.

Analysis of differential expression of lipid metabolism genes in atherosclerotic plaques in patients with coronary atherosclerosis

Aim. The goal of the study was to analyze the differential expression of lipid metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis.Material and Methods. The study was performed on the specimens of atherosclerotic plaques in 45–65-year-old patients with coronary atherosclerosis with stable exertional angina functional class II-IV without acute coronary syndrome. Coronary atherosclerosis was verified by coronary angiography. Atherosclerotic plaque tissue was sampled intraoperatively when indicated. Whole-genome sequencing of ribonucleic acid (RNA) was performed using the TruSeq RNA Sample Preparation Kit (Illumina, USA).Results. We analyzed the differences in the expression of 12 genes including LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, ABCA1, APOA1, APOE, LPL, SCARB1, and SREBF2 depending on the type of atherosclerotic plaques. The expression level of APOE gene was eight times higher in unstable atherosclerotic plaques of dystrophic-necrotic type (p < 0.0001). The expression levels of LDLR and APOB genes were eight times higher in stable atherosclerotic plaques (p < 0.0001). We did not find differences in the expression levels of the ABCG5, ABCG8, APOC3, CETP, CLPS, CYP7A1, and PNPLA5 genes.Conclusion. The study showed the differences in the activity of individual metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis. Obtained data may become the basis for the development of test systems aimed at predicting the development of atherosclerotic process and its complications.

Sodium‐Glucose Co‐Transporter 2 (SGLT2) Inhibitor Dapagliflozin Stabilizes Diabetes‐Induced Atherosclerotic Plaque Instability

Background Diabetes is known to accelerate atherosclerosis and increase plaque instability. However, there has been a lack of suitable animal models to study the effect of diabetes on plaque instability. We hypothesized that the tandem stenosis mouse model, which reflects plaque instability/rupture as seen in patients, can be applied to study the effects of diabetes and respective therapeutics on plaque instability/rupture. Methods and Results ApoE −/− mice at 7 weeks of age were rendered diabetic with streptozotocin and 5 weeks later were surgically subjected to tandem stenosis in the right carotid artery and fed with a high‐fat diet for 7 weeks. As a promising new antidiabetic drug class, a sodium glucose co‐transporter 2 inhibitor was tested in this new model. Diabetic mice showed an increase in the size of unstable atherosclerotic plaques and in the plaque instability markers MCP‐1, CD68, and necrotic core size. Mice treated with dapagliflozin demonstrated attenuated glucose and triglyceride levels. Importantly, these mice demonstrated plaque stabilization with enhanced collagen accumulation, increased fibrosis, increased cap‐to‐lesion height ratios, and significant upregulation of the vasculoprotective NADPH oxidase 4 expression. Conclusions The tandem stenosis mouse model in combination with the application of streptozotocin represents a highly suitable and unique mouse model for studying plaque destabilization under diabetic conditions. Furthermore, for the first time, we provide evidence of plaque‐stabilizing effects of sodium‐glucose co‐transporter 2 inhibitor. Our data also suggest that this newly developed mouse model is an attractive preclinical tool for testing antidiabetic drugs for the highly sought‐after potential to stabilize atherosclerotic plaques.