Atherosclerotic Plaques In Patients Research Articles

Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients

BackgroundLp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator.ObjectivesThis research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition.Materials and methodsSerum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded.ResultsIncreased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients.ConclusionsLevels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.

CXCL1 as a Potential Biomarker of Plaque Instability in Carotid Stenosis. Preliminary Report.

Biomarkers of atherosclerotic plaque instability are needed. This study aimed to evaluate the level of chemokine CXCL1 (CXC motif ligand 1) in plasma and atherosclerotic plaques in patients with carotid stenosis and correlate that with plaque morphology. The study group included 82 patients (30 women and 52 men) aged 50-90 years (mean 68.1 ± 8.9) who underwent elective carotid endarterectomy. The obtained atherosclerotic plaques were macroscopically and microscopically assessed according to the American Heart Association (AHA) classification. Fifty-one (62.2%) and 31 (37.8%) of the plaques were unstable and stable, respectively. The mean concertation of CXCL1 in plaques in asymptomatic and symptomatic patients was 0.00 (±0.00) vs 88.90 (±95.19) pg/ml, respectively (P = 0.000). The mean plasma concentration of CXCL1 in the study group was 42.40 (±85.79) pg/ml, while in the control group (healthy volunteers without lesions in the carotid arteries) it was 0.00 pg/mL (±0.00) (P = 0.000). The mean plasma CXCL1 concertation in asymptomatic and symptomatic patients was 22.08 (±49.13) versus 67.72 (±107.91) pg/ml, respectively (P = 0.031). Significantly higher CXCL1 concentration in atherosclerotic plaques and plasma in symptomatic patients compared with asymptomatic patients probably resulted from unstable lesions in the carotid arteries.

Cytokine Profiling of Plasma and Atherosclerotic Plaques in Patients Undergoing Carotid Endarterectomy.

Atherosclerotic plaques are sites of chronic inflammation with diverse cell contents and complex immune signaling. Plaque progression and destabilization are driven by the infiltration of immune cells and the cytokines that mediate their interactions. Here, we attempted to compare the systemic cytokine profiles in the blood plasma of patients with atherosclerosis and the local cytokine production, using ex vivo plaque explants from the same patients. The developed method of 41-plex xMAP data normalization allowed us to differentiate twenty-two cytokines produced by the plaque that were not readily detectable in free circulation and six cytokines elevated in blood plasma that may have other sources than atherosclerotic plaque. To verify the xMAP data on the putative atherogenesis-driving chemokines MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β (CCL4), RANTES (CCL5), and fractalkine (CX3CL1), qPCR was performed. The MIP1A (CCL3), MIP1B (CCL4), FKN (CX3CL1), and MCP1 (CCL2) genes were expressed at high levels in the plaques, whereas RANTES (CCL5) was almost absent. The expression patterns of the chemokines were restricted to the plaque cell types: the MCP1 (CCL2) gene was predominantly expressed in endothelial cells and monocytes/macrophages, MIP1A (CCL3) in monocytes/macrophages, and MIP1B (CCL4) in monocytes/macrophages and T cells. RANTES (CCL5) was restricted to T cells, while FKN (CX3CL1) was not differentially expressed. Taken together, our data indicate a plaque-specific cytokine production profile that may be a useful tool in atherosclerosis studies.

The value of Lp(a) and TG/HDLC in peripheral blood to assess the stability of carotid plaque in patients with ischemic stroke.

The objective of this study was to investigate the relationship between lipoprotein (a) (Lp(a)), triglyceride/high-density lipoprotein cholesterol (TG/HDL-C), and the stability of carotid atherosclerotic plaque in patients with acute ischemic stroke. A total of 142 patients with acute ischemic stroke were selected and divided into group A (59 cases of stable plaque formation) and group B (83 cases of unstable plaque formation) according to the characteristics of carotid artery plaque formation detected by carotid color Doppler ultrasound. The serum Lp(a), lipid metabolism indexes, peripheral blood routine indexes, and related serum inflammatory factors indexes were compared between the two groups. Receiver operating characteristic curve and multivariate logistic regression model were used to analyze the relationship between each index and the formation of carotid unstable plaque. There were no significant differences in serum total cholesterol (TC), HDL-C, and low-density lipoprotein cholesterol (LDL-C) between groups A and B (p > .05). The values of Lp(a), TG, and TG/HDL-C in group B were higher than those in group A, and the differences were statistically significant (p < .05). There were no significant differences in serum TC, HDL-C, and LDL-C between groups A and B (p > .05). The values of Lp(a), TG, and TG/HDL-C in group B were higher than those in group A, and the differences were statistically significant (p < .05). The values of HBA1C, Lp-PLA2, CRP, CysC, Hcy, TNF-α, neutrophils, and NLR in group B were higher than those in group A, and the differences were statistically significant (p < .05). There was no significant difference in FPG, systolic blood pressure, diastolic blood pressure, Hb, white blood cells, platelets, and lymphocytes between groups A and B (p > .05). The results of logistic regression model showed that the increase of Lp(a), TG/HDL-C, HBA1C, Lp-PLA2, CRP, CysC, Hcy, and NLR could increase the risk of carotid artery unstable plaque in patients with ischemic stroke (p < .05). Lp(a) and TG/HDL-C have certain value in evaluating the stability of carotid atherosclerotic plaque in patients with acute ischemic stroke, and the increased levels of LP (a) and TG/HDL-C will significantly increase the risk of carotid unstable plaque in patients.

Detection of monosodium urate depositions and atherosclerotic plaques in the cardiovascular system by dual-energy computed tomography

AimThe study aimed to explore the relationship between urate deposition and surrounding atherosclerotic plaques, and to confirm the contribution of urate deposition to the development of coronary atherosclerosis. Methods and resultsThe present study employed Dual-energy CT (DECT) material separation technology through calcium score scan to access the presence of MSU crystal deposition in coronary atherosclerotic plaques in patients with clinically suspected coronary heart diseases undergoing DECT. DECT showed that among 872 patients, 441 had plaques in coronary arteries; the incidence of plaque was 50.6 %. The patients were divided in the atherosclerotic plaque vs. non-plaque groups. There were significant differences in age, sex, blood pressure, blood glucose, serum creatinine, and history of gout and hyperuricemia between the plaque and non-plaque groups (all P < 0.05). Among the patients with coronary plaques, there were 348 patients (78.9 %) with simple atherosclerotic plaque (AP), 8 (1.8 %) with simple urate depositions (UD), and 85 (19.3 %) with urate depositions and atherosclerotic plaques (UDAP). The multivariable analysis showed that urate deposition was independently associated with plaques after adjustment for age, sex, blood pressure, blood glucose, serum creatinine, history of gout, and history of hyperuricemia (OR = 13.69, 95%CI: 7.53–22.95, P = 0.035). UPAP patients had significantly higher coronary calcium scores than AP patients [210.1 (625.2) AU vs 58.2 (182.5) AU, P < 0.001] Urate deposition (16.7 mm3) positively correlated with plaque calcification (73.8 mm³) in UPAP patients (r = 0.325, P < 0.001). ConclusionPatients with gout or a history of hyperuricemia were more likely to exhibit UDAP. Urate deposition was independently associated with plaques.

Metagenomic Analysis of Bacterial Microflora in Dental and Atherosclerotic Plaques of Patients With Internal Carotid Artery Stenosis.

Internal carotid artery stenosis is primarily attributed to atherosclerosis in the carotid artery bifurcation. Previous studies have detected oral bacteria in atherosclerotic lesions, suggesting an association between oral bacteria and atherosclerosis. In this study, we compared the bacterial flora of the atherosclerotic plaque in the carotid artery and dental plaque of patients with internal carotid artery stenosis using 16S ribosomal RNA (16S rRNA) metagenomic sequencing. Fifty-four patients who underwent internal carotid endarterectomy for internal carotid artery stenosis at the Showa University Hospital between April 2016 and February 2018 were included. Polymerase chain reaction targeting the 16S rRNA gene detected bacterial DNA in the carotid plaques of 11 cases, of which only 5 could be further analyzed. Thereafter, DNA extracted from the carotid and oral plaques of these 5 cases were analyzed using metagenomic sequencing targeting 16S rRNA. In addition, their general condition and oral conditions were evaluated. The patients were classified into symptomatic and asymptomatic groups based on the presence or absence of symptoms of transient ischemic attack, and their bacterial flora was evaluated. The results demonstrated that the microflora of carotid plaques (n = 5) contained bacterial species from 55 families and 78 genera. In addition, 86.5% of the bacteria detected in the carotid plaques were also detected in oral plaques. Cariogenic and periodontopathic bacteria accounted for 27.7% and 4.7% of the bacteria in the carotid plaques, respectively. These results suggest that oral bacteria are directly or indirectly involved in the pathogenesis of atherosclerosis. More extensive studies of oral commensal bacteria detected in extra-oral lesions are warranted to comprehensively investigate the role of oral bacteria in the pathogenesis of systemic diseases.

Microflora of atherosclerotic plaques and blood of patients with atherosclerosis

Background. Over the past decades, the role of the microbial factor in the development of atherosclerosis has been discussed. To date, data on the composition of the microflora of atherosclerotic plaques have been accumulated, but in these studies the blood microflora in atherosclerosis was not studied.&#x0D; Aim. To determine the contamination frequency of biopsy samples of atherosclerotic plaques and peripheral blood with cultured microorganisms in patients with atherosclerosis of the brachiocephalic arteries.&#x0D; Material and methods. A cross-sectional study in 35 patients with atherosclerosis of the carotid arteries; the average age of the patients was 58.2±8.3 years, was performed. Blood and atherosclerotic plaque samples from 23 men (mean age 58.6±10.3 years) and 12 women (mean age 57.3±14.3 years) were examined. Anaerobic flasks for blood cultivation were incubated at 35 °C for up to 6 months, from which they were regularly inoculated onto solid nutrient media to obtain culture growth. Cultures of tissues of atherosclerotic plaques of the carotid arteries in test tubes with thioglycollate medium were thermostated until visible growth of the culture was obtained; observation was carried out for up to 2 months. Identification of crops was carried out using commercial kits. For statistical analysis of the results obtained, the equality of the average values in two samples was checked using the Student’s statistical reliability test. Correlation analysis of the tightness of the connection was carried out using the Spearman rank correlation method.&#x0D; Results. The frequency of detection of microorganisms in samples of atherosclerotic plaques was 48.6% (17/35), including Cutibacterium acnes — in 31.4% (11/35), the genus Staphylococcus — in 22.9% (8/35), associations of these microorganisms — in 5.7% (2/35) of samples. C. acnes was cultured in the blood of 11.4% (4/35) of patients. In 5.7% (2/35) of patients, cultures of C. acnes bacteria were isolated from both atherosclerotic plaque biopsies and blood. Bacterial cultures exhibited slow growth on nutrient media. Correlation analysis of the closeness of the connection according to the Chaddock scale demonstrated the presence of a high and very high closeness of connection between the amount of high-density lipoproteins and the daily growth of C. acnes in atherosclerotic plaques (p=0.812) and blood (rxy=–0.969), the content of leukocytes showed a very high closeness of connection with days of growth of C. acnes in the blood (rxy=–0.957); Student's t-test revealed a statistically significant relationship with the fact of detection of C. acnes cultures in atherosclerotic plaques (p=0.013).&#x0D; Conclusion. Bacterial cultures isolated from blood samples and atherosclerotic plaques of patients with atherosclerosis had slow growth on nutrient media, and the period of their growth or the fact of detection correlated with the number of leukocytes and the level of high-density lipoproteins in the blood of patients.

Qualitative and quantitative ultrasound parameters of carotid atherosclerotic plaques in patients with moderate cardiovascular risk according to the SCORE scale: 7-year prospective follow-up study

Aim. To assess asymptomatic carotid atherosclerosis in patients with moderate cardiovascular risk over a 7-year prospective follow-up using non-invasive ultrasound markers.Material and methods. Eighty patients (47 men and 33 women) aged 53,1±5,9 years with moderate Systematic Coronary Risk Evaluation (SCORE) level, low-density lipoprotein cholesterol (LDL-C) of 2,7-4,8 mmol/l and asymptomatic hemodynamically insignificant (stenosis &lt;50%) carotid atherosclerosis (CA). Patients underwent CA ultrasound (PHILIPS IU22) at baseline and after 7 years. Plaque number, maximum plaque height, total plaque height, total CA stenosis, visual plaque morphology, gray-scale median (GSM), and intima- media thickness of the right and left common CAs were assessed. All patients were prescribed atorvastatin therapy at a dose of 10-40 mg until a target LDL-С level &lt;2,6 mmol/l was achieved.Results. During the follow-up period, a significant increase was noted in the number of plaques, the maximum and total plaque height, total CA stenosis, and intima- media thickness of the right and left common CAs. An increase in GSM was detected in 79% of plaques on statin therapy. Plaque echoicity increased by 4,90 [0,51; 17,41] (p &lt;0,001) or 7,2% [0,7%; 29%] (p&lt;0,001) over seven years. Regression analysis adjusted for sex and age showed the dependence of GSM changes (ΔGSM) on changes in the LDL-C level (ΔLDL-C) (p=0,049). With a decrease in LDL-C by 1 mmol/l, an increase in average GSM was noted by 5,9 (0,03-11,78). The maximum plaque height increased significantly after 7-year follow-up from 1,80 [1,50; 2,20] to 2,00 [1,63; 2,68] mm (p=0,044). In patients who reached a LDL-C level of 1,8 mmol/l, the maximum plaque height decreased more than in patients who did not reach this level (-0,07 [-0,45; 0,14] mm and 0,20 [-0,05; 0,40] mm, respectively (p=0,028)). Regression analysis adjusted for sex and age did not reveal a relationship between the change of maximum plaque height with ΔLDL-C and Δhigh-density lipoprotein cholesterol, but with LDL-C level after 7 years.Conclusion. Statin therapy in patients with CA stenosis &lt;50% stabilizes the plaques due to echogenicity increase. LDL-C &lt;1,8 mmol/l can lead to a decrease in maximum plaque height.

Adipokine-Cytokine Profile in Patients with Unstable Atherosclerotic Plaques and Abdominal Obesity.

The study included 145 men aged 38-79 with atherosclerosis of the coronary arteries (CA) and stable angina pectoris II-III FC who were hospitalized for coronary bypass surgery (2011-2022). The final analysis included 116 patients. Notably, 70 men had stable plaques in the CA (of which 44.3% had AO), and 46 men had unstable plaques in the CA (of which 43.5% had AO). Adipocytokine levels were determined using multiplex analysis (Human Metabolic Hormone V3 panel). In the subgroup of patients with unstable plaques, patients with AO had a GLP-1 level that was 1.5 times higher and a lipocalin-2 level that was 2.1 times lower, respectively. GLP-1 is direct, and lipocalin-2 is inversely associated with AO in patients with unstable plaques. Among patients with AO, the level of lipocalin-2 in patients with unstable plaques was 2.2 times lower than in patients with stable plaques in the CA. The level of lipocalin-2 was inversely associated with the presence of unstable atherosclerotic plaques in the CA. GLP-1 is directly associated with AO in patients with unstable atherosclerotic plaques. Lipocalin-2 is inversely associated with unstable atherosclerotic plaques in patients with AO.

Abstract 338: Novel Role Of Endothelial Cd47 In The Regulation Of Pathogenesis Of Atherosclerosis

Background: The anti-phagocytic molecule CD47 is upregulated in atherosclerotic plaques of patients with cerebrovascular disease. However, the role of endothelial cell-specific CD47 in the pathogenesis of atherosclerosis has not yet been defined. Kojima et.al . described atheroprotective effect of anti-CD47 antibody by enhancing efferocytosis in atherosclerosis. In this study, we determined whether endothelialCD47 regulates efferocytosis in atherosclerosis. Methods: Susceptibility to atherosclerosis was evaluated in cross sections of the aortic sinus in atherosclerotic mice. Using single-cell RNA sequencing and efferocytosis assays, we investigated the role of CD47 in regulating efferocytosis in atherosclerotic mouse model. Results: Endothelial cell-specific deletion of CD47 led to significant plaque reduction in aortic sinus of athero-CD47iECKO mice. Cluster analysis and gene expression profiles of 20,000 aortic endothelial cells from atherosclerotic mice identified 10 major cell types: endothelial cells, VSMCs, fibroblasts, B cells, T cells, macrophage, erythrocytes, oligodendrocytes cells, Schwann cells, and pericytes. In athero-CD47iECKO group, subpopulation of endothelial cells as well as fibroblasts, T-cells, B-cells, macrophages, erythrocytes, oligodendrocytes, and pericytes were increased, while vascular smooth muscle cell numbers decreased. Using efferocytosis assay on isolated primary endothelial cells from control and CD47iECKO mice, we observed CD47 deletion induced engulfment of apoptotic Jurkat cells, which had been exposed to NF-κB inhibitor, BAY11-7082 to stimulate apoptotic attributes. Quantitative PCR analyses showed that CD47 deletion increases the expression of efferocytosis receptor FasL, CX3CL1, Gpr132, MerTK, Scarb1, Sirpa, TSP1, and HMGB1. Conclusion: Our study indicates that genetic deletion of CD47 in endothelial cells attenuates atheroma progression by enhancing efferocytosis. This study also reveals phenotypic heterogenicity of endothelial cells at the single-cell level during atherogenesis and provides deeper understanding of endothelial cell biology in atherosclerosis that may facilitate the development of novel therapeutic interventions for cardiovascular disease.

Characteristics of coronary artery ectasia and accompanying plaques: an optical coherence tomography study

Coronary artery ectasia (CAE) in adults is often caused by atherosclerotic plaques. CAE can affect atherosclerotic plaques through hemodynamic changes. However, no study has evaluated the characteristics of CAE with atherosclerotic plaques. Therefore, we aimed to disclose the characteristics of atherosclerotic plaques in patients with CAE using optical coherence tomography (OCT). We evaluated patients with CAE, confirmed by coronary angiography, who underwent pre-intervention OCT between April 2015 and April 2021. Each millimeter of the OCT images was analyzed to assess the characteristics of CAEs, plaque phenotypes, and plaque vulnerability. A total of 286 patients (344 coronary vessels) met our criteria, 82.87% of whom were men. Right coronary artery lesions were the most common, comprising 44.48% (n = 153) of the total. We found 329 CAE vessels with plaques, accounting for 95.64% of the coronary vessels. After grouping CAEs and plaques by their relative positions, we found that the length of plaques within CAE lesions was longer than that of plaques in other sites (P < 0.001). Plaques within CAE lesions had greater maximum lipid angles and lipid indexes (P = 0.007, P = 0.004, respectively) than those on other sites. This study revealed the most common vascular and morphological characteristics of CAE. While the accompanying plaques were not affected by the location or morphology of the CAE vessels, they were affected by their position relative to the CAE lesion.

Quantitative evaluation for intravascular structures of vertebral artery dissection with a novel zoomed high-resolution black-blood MR imaging.

Although non-stroke vertebral artery dissection (VAD) is diagnosed using MRI, detecting the subtle intravascular structure remains challenging. This study aimed to evaluate the validity of quantitative intravascular scanning based on novel zoomed high-resolution black blood (Z-HB) MRI for distinguishing VAD from other vessel pathologies. Twenty-one patients with non-stroke VAD and 18 with symptomatic atherosclerotic plaques in their vertebral artery underwent Z-HB MRI and subsequent profile curve processing. Axial Z-HB imaging was obtained from dissected and normal segments in patients with VAD and atherosclerotic plaque in patients with ischemia. We investigated the qualitative categorization of the scanning patterns of the intravascular signals. We also evaluated the quantitative ability of each profile curve to discriminate multiple vessel pathologies by analyzing the receiver operating characteristics curves. Profile curve processing of 140 Z-HB images categorized the intravascular signal patterns into luminal, asymmetrical, and omega types. The asymmetrical type included both dissecting and atherosclerotic vessels, and the omega type included dissecting and normal vessels. In the asymmetrical type, quantitative evaluation successfully distinguished intramural hematomas of VAD from atherosclerotic plaque with an area under the curve of 0.80. The intimal flap of the VAD was distinguished from the blood flow artifact of the normal vessel with an area under the curve of 0.93 in the omega type. A combination of novel Z-HB MRI and profile curve processing provided an ultra-high-resolution analysis of the intravascular structure of non-stroke VAD and successfully distinguished VAD from normal vessels or atherosclerotic plaques.

Abstract 13609: Heterogeneous Populations of Cytotoxic CD4 T Cells Are Expanded in Atherosclerotic Plaques of Patients With Type 2 Diabetes

Introduction: Atherosclerotic cardiovascular disease (ACVD) is the main cause of morbidity and mortality in patients with type 2 diabetes (T2D). ACVD is more severe and diffuse in T2D than in subjects with no diabetes (ND). Moreover, cholesterol reduction in T2D leads to less plaques resolution. While the role of macrophages in T2D plaque pathology has been investigated, no studies have systematically investigated the heterogeneity of CD4 T cells in human plaques. Hypothesis: Plaques of patients with T2D have a greater CD4 T cell heterogeneity and pathogenic phenotypes compared with plaques of ND subjects. Methods: To identify the specific T cell alterations in plaques we analyzed scRNA sequencing data of &gt;80,000 plaque immune cells from 22 patients undergoing carotid endarterectomy with or without T2D (54.5% T2D). Results: Unbiased clustering of CD45+ cells identified a total of 24 immune cell clusters, including CD4 T cells that presented similar cell frequencies between T2D (~11%) and ND patients (~10%). CD4 T cells comprise 7 clusters: naïve, proliferating, central memory (CM), effector memory (EM), T regulatory (Tregs), cytotoxic (CTL), and gamma delta (γδ) T cells. CD4 CTLs expressed GZMB, GNLY, PRF1 , and could be divided into TRAC +EM (cluster 9) and CTLγδ T cells expressing both TRDC and TRGC2 (cluster 5). CTLγδ T cells were significantly expanded in T2D plaques (p=0.032), and expressed high levels of GZMA and transcription factors involved in T cell differentiation such as RUNX and TBX21 . These CTLγδ T cells are enriched with sets of genes involved in T-cell activation, numerous pathways of apoptosis, cytotoxicity, chemotaxis and cytokine signaling (i.e. IL1, IL2, IL9 ). Conclusions: Our data show that plaques from patients with T2D are highly enriched in unique CTL/γδ T cells and suggest that their cytotoxic potential may contribute to the increased cardiovascular risk of subjects with T2D.

Morphological features of structural rearrangement of atherosclerotic plaque in patients with occlusive-stenotic diseases of the main arteries

Annotation. According to the set goal of the work, we analyzed the results of morphological studies of atherosclerotic plaque in patients with occlusive-stenotic diseases of the arteries of the lower extremities as a consequence of obliterating atherosclerosis. The material of the study was fragments of the arteries of 12 patients affected by atherosclerotic plaque, taken during open surgical interventions on different arterial segments, and in 8 cases, autopsy material of atherosclerotic plaques of the femoral and tibial arteries was selected. The histological research method is applied. It is established that atherosclerotic plaque in the process of its development goes through a number of stages from lipid spot to atheromatosis, calcification and fibrosis with the development of complications such as ulceration, hemorrhage, thrombosis. In addition, the severity of atherosclerotic plaque leads to vascular stenosis and significant local or systemic hemodynamic changes, and thus determines the indications for a particular type of surgery for occlusive-stenotic diseases of the main arteries.

Association between circulating asprosin levels and carotid atherosclerotic plaque in patients with type 2 diabetes

BackgroundCarotid plaque is one of the typical manifestations and precursors of diabetic cardiovascular complications. As a new adipokine, asprosin participates in the development of diabetes and cardiovascular diseases, and is considered to be closely related to insulin resistance and glucolipid metabolism. This study aimed to analyze the relationship between serum asprosin level and carotid plaque in patients with type 2 diabetes mellitus (T2DM). MethodsA total of 180 patients with T2DM were selected. The basic parameters and biochemical indexes of the subjects were measured, and the serum asprosin concentration of the subjects was detected by ELISA. The carotid plaque was evaluated by color Doppler ultrasound. ResultsThe level of serum asprosin in the T2DM with carotid plaque group was significantly higher than that in T2DM without carotid plaque group [2.53(1.73–3.21) vs 1.72(1.23–2.34) ng/mL, P < 0.05]. The incidence of carotid plaque in the low, middle and high quartiles was 31.7 %, 48.3 % and 70 % respectively. Correlation analysis showed that serum asprosin was positively correlated with BMI, WHR, SBP, DBP, FIns, LDL-C, HOMA-IR, and HOMA-β (P < 0.05). Linear regression analysis showed that WHR, DBP, FIns, and LDL-C were independent influencing factors of asprosin. Logistic regression analysis showed that serum asprosin was still significantly correlated with carotid plaque in T2DM patients after adjusting for multiple confounding factors. The area under receiver-operating curve (ROC) of asprosin predicting carotid plaque was 0.701 (0.625–0.777) in T2DM. ConclusionThe level of serum asprosin in T2DM patients with carotid plaques is significantly higher, suggesting that asprosin may play a role in the occurrence and development of carotid plaques in T2DM. Detection of this index can provide new clinical evidence for the prevention and treatment of diabetic cardiovascular disease.

Protein carbamylation associates with collagen in atherosclerotic plaque and impacts macrophage functions

Background and Aims : Carbamylation is a post-translational protein modification increased in CKD patients as well as in late-stage atherosclerotic plaques in patients without CKD. Carbamylation was shown to cause pro-atherogenic alteration in plasma proteins and was significantly associated with increased mortality in CKD patients. However, the exact mechanisms and role of protein carbamylation in atherogenesis are not known.

TCF7 is highly expressed in immune cells on the atherosclerotic plaques, and regulating inflammatory signaling via NFκB/AKT/STAT1 signaling.

Atherosclerosis, which is the fundamental basis for cardiovascular diseases in the global world, is driven by multiple roles of the immune system in the circulation and vascular plaque. Recent studies demonstrated that T-cell infiltrates into aorta plaque and plays an important role in recruiting macrophages to the vascular wall. Here, using single-cell sequencing, we found T cells in patients’ plaques and differentially expressed genes (DEGs) of T cells in atherosclerosis mice. T cells and macrophages were continuously activated in atherosclerotic plaque in patients. Besides, other immune cells also take part in atherogenesis, such as natural killer (NK) cells, granulocytes. Interferon (IFN)/NFκB signaling, the AKT signaling pathway was highly activated in mouse (in vivo) and cell line (in vitro). TCF7 and XCL1 were regulated by AKT and NFκB, respectively through protein–protein network analysis. Therefore, we attempt to clarify and discover potential genes and new mechanisms associated with atherosclerosis for drug development.

Signature transcriptome analysis of stage specific atherosclerotic plaques of patients

BackgroundInflammation plays an important role in all the stages of atherosclerotic plaque development. The current study aimed at assessing the altered expression of genes functioning in inflammation within the early stage (ES) and advanced stage (AS) atherosclerotic plaques obtained from patients undergoing coronary artery bypass grafting (CABG) surgery and identifying biomarker panel/s that may detect the status of plaque stages using peripheral blood samples.MethodsA section of ES and AS plaques and normal left internal mammary arteries (LIMA) were obtained from 8 patients undergoing the CABG surgery. Total RNA isolated was analyzed for mRNA and miRNA expression profile by Affymetrix arrays. A significant number of mRNAs was found to be differentially expressed in ES and AS plaque tissues relative to LIMA. The pathway analysis of differentially expressed mRNAs in the two plaque stages was also performed using DAVID Bioinformatics Database.ResultsThe mRNAs were found to be involved in critical inflammatory processes such as the toll-like receptor signaling pathway and cytokine-cytokine receptor interaction. Few miRNAs targeting these mRNAs were also altered in the two plaque conditions. QRT-PCR results showed a similar expression pattern of a few of the mRNAs and miRNAs in peripheral blood of the same patients relative to healthy controls.ConclusionChanges in mRNA and miRNA expression associated with various inflammatory processes occur in different atherosclerotic stage plaques as well as peripheral blood. Detection of such variations in patients’ blood can be used as a possible prognostic tool to detect and/or predict the risk and stage of atherosclerosis.

Serum Lipocalin-2 Levels Are Increased and Independently Associated With Early-Stage Renal Damage and Carotid Atherosclerotic Plaque in Patients With T2DM.

ObjectivesDiabetic nephropathy (DN), one of the major complications of diabetes mellitus, is the major cause of end-stage renal failure that finally increases the risk of cardiovascular disease and mortality. The aim of this study is to explore the relationship between serum lipocalin-2 (LCN-2) levels and DN and carotid atherosclerotic plaque (CAP) in patients with type 2 diabetes mellitus (T2DM).MethodsWe have performed a prospective study of 749 T2DM patients with or without DN. Blood samples were collected and used to test serum LCN-2 levels, renal function, as well as biochemical parameters. CAP in these subjects was determined by ultrasonography.ResultsIn these 749 subjects with T2DM, an increased morbidity of CAP was observed in T2DM patients with DN as compared with those without this complication (P < 0.05). Interestingly, serum LCN-2 levels were significantly increased in T2DM patients with DN or CAP compared with T2DM alone [97.71 (71.49-130.13) vs. 77.29 (58.83-115.05) ng/ml, P < 0.001]. In addition, serum LCN-2 levels in T2DM patients with DN and CAP were significantly higher than that of T2DM patients with DN or CAP [131.37 (101.43-182.04) vs. 97.71(71.49-130.13) ng/ml, P < 0.001]. Furthermore, serum LCN-2 levels were positively correlated with hemoglobin A1c, systolic blood pressure, hypertension, CAP, and DN, as well as renal function factors including uric acid, creatinine, the estimated glomerular filtration rate, and urinary albumin-to-creatinine ratio, respectively (P < 0.05), but negatively correlated with HDL-c (P < 0.05). The multinomial logistic regression analysis showed that serum LCN-2 was independently associated with DN and CAP in patients with T2DM after the adjustment for risk factors (P < 0.001).ConclusionsEarly-stage renal damage is a risk factor associated with the incidence of CAP in patients with T2DM. Serum LCN-2 is significantly increased and associated with early-stage renal damage and the incidence of CAP in patients with T2DM.

Cardiovascular events and atherosclerosis in patients with type 2 diabetes and impaired glucose tolerance: What are the medical treatments to prevent cardiovascular events in such patients?

Type 2 diabetes mellitus and impaired glucose tolerance (IGT) significantly induce advanced coronary artery disease and systemic atherosclerosis. Thus, type 2 diabetes mellitus and IGT are traditional risk factors of cardiovascular disease. In contrast, acute coronary syndrome is frequently caused by the rupture of coronary atherosclerotic plaques, which reduces patients’ quality of life and might result in death. To date, many trials have sought to identify ways to determine the coronary plaque volume and its vulnerability, and many studies have shown that some specific antihyperglycemic agents might prevent coronary or carotid plaque progression, decrease plaque volume, induce plaque stability, and improve clinical outcomes in patients with type 2 diabetes mellitus and IGT. This article reviews the following: (i) the association between coronary or carotid plaques and abnormal glucose tolerance, including type 2 diabetes mellitus; and (ii) the effects of oral antihyperglycemic drugs to improve clinical outcomes and stabilize atherosclerotic plaques in patients with type 2 diabetes mellitus and IGT.