Atherosclerosis Research Articles

Macrophages Unmasked: Their Pivotal Role in Driving Atherosclerosis in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that significantly increases the risk of cardiovascular diseases, particularly atherosclerosis (AS). Understanding the shared pathogenic mechanisms underlying SLE and AS is crucial for developing effective therapeutic strategies. Macrophages, as pivotal immune cells, play a critical role in the initiation and progression of atherosclerotic plaques within the context of SLE. This review delves into the molecular and cellular mechanisms governing macrophage activation and differentiation in response to SLE-related inflammatory mediators, highlighting their roles in lipid metabolism, plaque stability, and immune regulation. Additionally, we discussed the current treatment modalities for SLE and their impact on macrophage functionality, exploring these effects for atherosclerotic progression. By elucidating the intricate relationship between macrophages, SLE pathophysiology, and AS progression, this review underscores the need for a multidisciplinary approach in managing SLE and its cardiovascular complications, aiming to improve patient survival and quality of life through tailored therapeutic interventions addressing both autoimmune and cardiovascular pathologies.

Transcription Factor Blimp-1: A Central Regulator of Oxidative Stress and Metabolic Reprogramming in Chronic Inflammatory Diseases

B-lymphocyte-induced maturation protein 1 (Blimp-1) is a transcription factor that, among other functions, modulates metabolism and helps to regulate antioxidant pathways, which is important in the context of chronic inflammatory diseases like diabetes, cardiovascular disease, and autoimmune disease. In immune cell function, Blimp-1 has a modulatory role in the orchestration of metabolic reprogramming and as a promoter of anti-inflammatory cytokines, including IL-10, responsible for modulating oxidative stress and immune homeostasis. Moreover, Blimp-1 also modulates key metabolic aspects, such as glycolysis and fatty acid oxidation, which regulate reactive oxygen species levels, as well as tissue protection. This review depicts Blimp-1 as an important regulator of antioxidant defenses and anti-inflammation and suggests that the protein could serve as a therapeutic target in chronic inflammatory and metabolic dysregulation conditions. The modulation of Blimp-1 in diseases such as diabetic coronary heart disease and atherosclerosis could alleviate oxidative stress, augment the protection of tissues, and improve disease outcomes. The therapeutic potential for the development of new treatments for these chronic conditions lies in the synergy between the regulation of Blimp-1 and antioxidant therapies, which are future directions that may be pursued. This review emphasizes Blimp-1’s emerging importance as a novel regulator in the pathogenesis of inflammatory diseases, providing new opportunities for therapeutic intervention.

CircRNAs increase during vascular cell differentiation and are biomarkers for vascular disease.

The role of circular RNAs (circRNAs) and their regulation in health and disease are poorly understood. Here, we systematically investigated the temporally resolved transcriptomic expression of circRNAs during differentiation of human induced pluripotent stem cells (iPSC) into vascular endothelial cells (EC) and smooth muscle cells (SMC) and explored their potential as biomarkers for human vascular disease. Using high-throughput RNA sequencing and a de novo circRNA detection pipeline, we quantified the daily levels of 31,369 circRNAs in a two-week differentiation trajectory from human stem cells to proliferating mesoderm progenitors to quiescent, differentiated EC and SMC. We detected a significant global increase in RNA circularization, with 397 and 214 circRNAs upregulated > 2 fold (adjusted P < 0.05) in mature EC and SMC, compared with undifferentiated progenitor cells. This global increase in circRNAs was associated with upregulation of host genes and their promoters and a parallel downregulation of splicing factors. Underlying this switch, the proliferation-regulating transcription factor MYC decreased as vascular cells matured, and inhibition of MYC led to downregulation of splicing factors such as SRSF1 and SRSF2 and changes in vascular circRNA levels. Examining the identified circRNAs in arterial tissue samples and in peripheral blood mononuclear cells (PBMC) from patients, we found that circRNA levels decreased in atherosclerotic disease, in contrast to their increase during iPSC maturation into EC and SMC. Using machine learning, we determined that a set of circRNAs derived from COL4A1, COL4A2, HSPG2, and YPEL2 discriminated atherosclerotic from healthy tissue with an AUC of 0.79. CircRNAs from HSPG2 and YPEL2 in blood PBMC samples detected atherosclerosis with an AUC of 0.73. Time-resolved transcriptional profiling of linear and circular RNA species revealed that circRNAs provide granular molecular information for disease profiling. The identified circRNAs may serve as blood biomarkers for atherosclerotic vascular disease.

Is Insulin Resistance an Independent Predictor of Atherosclerosis?

Background: Insulin resistance (IR) is a condition that precedes the onset of type 2 diabetes mellitus (T2DM), which is regarded as an established risk factor for atherosclerosis (AS). Considering that the same metabolic changes as those caused by IR are evidenced to promote the development of AS, we investigated whether IR estimated by the homeostasis model assessment of IR (HOMA-IR) could predict the occurrence of preclinical AS. Methods: The study participants were divided into two groups based on the presence of IR diagnosed during the baseline hospitalization and defined as a HOMA-IR value equal to or higher than 2.5. After a follow-up period of at least four years, a total of 79 (n = 79) were prospectively assessed in terms of the presence of preclinical AS, determined by either an abnormally low ankle–brachial index (ABI) (ABI &lt; 0.9) or an increased carotid intima media thickness (CIMT) (CIMT &gt; 1 mm). Results: Using the multivariate logistic regression analysis, it was demonstrated that the HOMA-IR was associated with an abnormally low ABI (odds ratio: 1.609, 95% confidence interval (CI): [1.041–2.487], p = 0.032). The Cox regression model revealed that the HOMA-IR was a predictor of both an abnormal ABI (hazard ratio: 1.435, CI: [1.076–1.913], p = 0.014) and increased CIMT (hazard ratio: 1.419, CI: [1.033–1.948], p = 0.031), independently of age, sex, dyslipidemia, smoking, triglycerides (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL), and total cholesterol levels. Conclusions: IR, as estimated by the HOMA-IR, may be considered as a predictor of preclinical AS, independently of cardiovascular risk factors.

Deficiency of Calpain-1 attenuates atherosclerotic plaque and calcification and improves vasomotor dysfunction in Apolipoprotein E knockout mice through inhibiting inflammation.

Atherosclerosis (AS) and atherosclerotic calcification (AC) are closely related to the cardiovascular diseases, largely due to its induction of vasomotor dysfunction. We previously reported that Calpain-1 inhibitor attenuated AS and AC. The present study was designed to investigate the effects and potential mechanisms of Calpain-1 knockout (Calpain-1 KO) in Apolipoprotein E KO (ApoE KO) mice on AS, AC, aortic vasomotor function as well as the liver dysfunction. We hybridized ApoE KO mice with Calpain-1 KO mice to obtain ApoE/Calpain-1 double KO (A×C DKO) mice. The formation of AS and AC was evaluated and liver function was determined. Aortic vasomotor function was assessed. Contents of TNF-α, IL-6, IL-18, IL-1β and NO and the activity of AST, ALT, ALP and eNOS in serum were quantified. The mRNA expression of CD68, SR-A, CD36, PPAR-γ, LXR-α, ABCA1, BMP-2, OPN, ALP and Runx2 in aorta and/or liver were measured. The results showed that in comparison to C57 mice, ApoE KO mice demonstrated the significant increases in the areas of AS and AC, the increases in the mRNA expression of CD68 in the aorta, the increases in the AST, ALT and ALP activity in serum. ApoE KO mice also showed the dysfunction of the aortic contraction induced by phenylephrine and of the relaxation induced by acetylcholine. However, compared with ApoE KO mice, A×C DKO mice exhibited the significant attenuation of AS and AC and the downregulation of mRNA expression of CD68 in aorta. A×C DKO mice revealed the reduction of AST, ALT and ALP activity in serum, the improvements in aortic contraction and relaxation as well as the increases in eNOS activity and NO content in serum. A×C DKO mice also showed the decreases in the contents of TNF-α, IL-6, IL-18 and IL-1β in serum. The mRNA expression of CD68 in aorta, SR-A and CD36 in both aorta and liver of A×C DKO mice was downregulated, while that of PPAR-γ, LXR-α, and ABCA1 was upregulated in comparison of ApoE KO mice. In addition, the mRNA expression of BMP-2, OPN, ALP and Runx2 in aorta of A×C DKO mice was downregulated in comparison of ApoE KO mice. The results suggested that deficiency of Calpain-1 attenuated the formation of AS and AC and improved vasomotor and liver dysfunction in ApoE KO mice through anti-inflammation, and modulation of the mRNA expression of genes related to AS and AC.

NCOA4 linked to endothelial cell ferritinophagy and ferroptosis:a key regulator aggravate aortic endothelial inflammation and atherosclerosis.

Atherosclerosis (AS) is associated with a high incidence of cardiovascular events, yet the mechanisms underlying this association remain unclear. Our previous study found that Atherosclerotic endothelial injury is closely associated with ferroptosis in ApoE-/- mice. Ferroptosis is a novel mode of cell death induced by decreased antioxidant capacity of the organism and accumulation of reactive oxygen species. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is an important regulator of sudden ferroptosis in cells. However, the role of NCOA4 in AS and the exact mechanism by which it regulates the ferritinophagy response remain unclear. Herein, we report that NCOA4 expression is elevated in ApoE-/- mice and endothelial cells and is significantly correlated with AS. NCOA4 expression promoted ferroptosis, and was positively correlated with ferritinophagy response. Mechanistically, our findings indicate that LOX-1 is a key upstream target that influences the function of NCOA4. The specific pathway is related to the activation of cGAS-STING signaling to upregulate NCOA4 expression. Moreover, our findings demonstrate the "Gualou-Xiebai" herb pair can regulate LOX-1 to inhibit ferroptosis. Collectively, our results provide evidence of a connection between NCOA4-mediated promotion of AS and suggest that targeting upstream molecules regulating NCOA4 could be a potential therapy for AS.

Low shear stress induces vascular endothelial cells apoptosis via miR-330 /SOD2 /HSP70 signaling pathway.

Atherosclerosis (AS) is a chronic disease initiated by vascular endothelial dysfunction, with low shear stress (SS) being a critical inducing factor in this dysfunction. Apoptosis, a form of programmed cell death, is closely associated with AS progression. However, the impact of low SS on endothelial apoptosis and its specific molecular mechanisms remains unclear. Our study revealed that low SS induces apoptosis in endothelial cells and contributes to endothelial dysfunction. Under low SS conditions, miR-330 expression was markedly upregulated, which subsequently targeted and inhibited SOD2 expression, leading to ROS accumulation and oxidative stress. Overexpression of SOD2 under low SS conditions markedly elevated HSP70 expression, contributing to endothelial homeostasis. However, when HSP70 expression was inhibited in the context of SOD2 overexpression, there was a significant increase in pro-apoptotic proteins (BAX and cleaved-caspase-3) and total apoptosis rate, along with a significant reduction in endothelial function markers such as nitric oxide and endothelial nitric oxide synthase. Notably, our experiments indicated no direct interaction between SOD2 and HSP70. Furthermore, inhibiting ROS production significantly raised HSP70 expression, suggesting that SOD2 regulates HSP70 in an indirect process involving ROS. In summary, our findings elucidate that low SS induces endothelial apoptosis and dysfunction through the miR-330/SOD2/HSP70 signaling pathway, providing valuable insights into AS intervention and prevention.

Lipidomics-based investigation of its impact on the pathogenesis of coronary atherosclerosis: a Mendelian randomization study

BackgroundConsiderable attention has been devoted to investigating the association between lipid metabolites and cardiovascular diseases, particularly coronary atherosclerosis.MethodsA two-sample MR framework was used to investigate the relationship between lipid metabolites and the risk of coronary atherosclerosis. Two GWAS datasets were examined to take intersections of SNPs from 51,589 cases and 343,079 controls, and 14,334 cases and 346,860 controls to determine genetic susceptibility to coronary atherosclerosis. Random-effects inverse variance weighted (IVW) MR analyses were performed by a series of sensitivity assessments to measure the robustness of our findings and to detect any violations of MR assumptions.ResultsThrough IVW, MR-Egger and weighted median regression methods, we inferred that these six lipid metabolites: cholesterol levels, sterol ester (27:1/18:2) levels, triacylglycerol (52:4) levels, triacylglycerol (52:5) levels, diacylglycerol (18:1_18.2) levels, triacylglycerol (53:4), could directly impact the development of atherosclerosis.ConclusionIn conclusion, our study comprehensively illustrates a causal relationship between lipid metabolites and the risk of coronary atherosclerosis. Furthermore, cholesterol levels, sterol ester (27:1/18:2) levels, triacylglycerol (52:4) levels, triacylglycerol (52:5) levels, diacylglycerol (18:1_18.2) levels, and triacylglycerol (53:4) levels are positively correlated with the risk of coronary atherosclerosis. These six lipid metabolites have the potential as new predictors of the risk of atherosclerosis, providing new insights into the treatment and prevention of cardiovascular diseases.

Regulated cell death in acute myocardial infarction: Molecular mechanisms and therapeutic implications.

Acute myocardial infarction (AMI), primarily caused by coronary atherosclerosis, initiates a series of events that culminate in the obstruction of coronary arteries, resulting in severe myocardial ischemia and hypoxia. The subsequent myocardial ischemia/reperfusion (I/R) injury further aggravates cardiac damage, leading to a decline in heart function and the risk of life-threatening complications. The complex interplay of multiple regulated cell death (RCD) pathways plays a pivotal role in the pathogenesis of AMI. Each RCD pathway is orchestrated by a symphony of molecular regulatory mechanisms, highlighting the dynamic changes and critical roles of key effector molecules. Strategic disruption or inhibition of these molecular targets offers a tantalizing prospect for mitigating or even averting the onset of RCD, thereby limiting the extensive loss of cardiomyocytes and the progression of detrimental myocardial fibrosis. This review systematically summarizes the mechanisms underlying various forms of RCD, provides an in-depth exploration of the pathogenesis of AMI through the lens of RCD, and highlights a range of promising therapeutic targets that hold the potential to revolutionize the management of AMI.

ANMCO/GISE/SICOA Consensus document: Role of coronary computed tomography angiography in chronic coronary syndromes

Chronic coronary syndromes (CCS) are the most common clinical manifestation of coronary atherosclerosis. Coronary computed tomography angiography (CCTA) is a recent innovation in non-invasive cardiac imaging. It is the only anatomical imaging method that allows direct visualization of the coronary lumen, vessel walls, and atherosclerotic plaques, offering high sensitivity and a strong negative predictive value. CCTA is particularly useful in identifying or ruling out coronary atherosclerosis in the context of CCS and serves as an excellent filter for invasive coronary angiography. Compared to other non-invasive functional imaging tests (stress echocardiography, single photon emission computed tomography, magnetic resonance imaging, positron emission tomography), CCTA provides detailed characterization of both obstructive and non-obstructive plaques, enabling accurate risk stratification and guiding therapy. Recent advances in computed tomography technology and imaging techniques further extend the use of CCTA beyond plaque and stenosis evaluation, offering also functional lesion information. This consensus document aims to detail the technical aspects of CCTA and illustrate its role in optimizing CCS diagnostic and therapeutic management, enhancing precision medicine and personalized patient care.

Coronary artery calcifications are not associated with epicardial adipose tissue volume and attenuation on computed tomography in 1,945 individuals with various degrees of glucose disorders.

The quantification of coronary artery calcifications (CAC) is a mainstay in radiological assessment of coronary atherosclerosis and cardiovascular risk, but reflect advanced, possibly late-stage changes in the arteries. Increased volume and changes in attenuation of the epicardial adipose tissue (EAT) on computed tomography (CT) have been linked to adverse cardiovascular events, and these changes in the EAT might reflect earlier stages of the processes leading to clinically manifest atherosclerosis. The relationship between EAT and CAC is subject to a knowledge gap, especially in individuals with no previously known coronary artery disease. Fully automated EAT analysis with an artificial intelligence-based model was performed in a population sample enriched for pre-diabetics, comprising a total of 1,945 individuals aged 50-64years, where non-contrast CT images, anthropometric and laboratory data was available on established cardiovascular risk factors. Uni- and multivariable linear regression, gradient-boosting and correlation analyses were performed to determine the explanatory value of EAT volume and attenuation data with regards to CAC data. Neither EAT volume nor EAT attenuation was associated with the presence or severity of CAC, when adjusting for established cardiovascular risk factors, and had only weak explanatory value in gradient-boosting and correlation analyses. Age was the strongest predictor of CAC in both sexes. No independent association was found between CAC and total EAT volume or attenuation. Importantly, these findings do not rule out early stage or local effects on coronary atherosclerosis from the EAT immediately surrounding the coronary arteries.

Flow Mediated Dilation and Its Correlation with Coronary and Systemic Atherosclerosis in Patients Scheduled for Surgical Myocardial Revascularization

Flow Mediated Dilation and Its Correlation with Coronary and Systemic Atherosclerosis in Patients Scheduled for Surgical Myocardial Revascularization

Abstract TMP98: Low-dose Rivaroxaban plus Antiplatelet Treatment in Patients With Symptomatic Intracranial Atherosclerotic Stenosis：A Prospective Observational Study

Background: The secondary prevention of symptomatic intracranial atherosclerotic stenosis (sICAS) remains a significant challenge. In the recent COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial, the combination of low-dose rivaroxaban with antiplatelet therapy demonstrated better efficacy in preventing vascular events in patients with coronary atherosclerosis compared to antiplatelet therapy alone. This study aimed to evaluate the efficiency of dual pathway inhibition on recurrent stroke and vascular events in patients with sICAS. Methods: Patients with sICAS admitted within 7 days of symptom onset were identified from the hospital-based database from January 2019 to June 2023. We compared the clinical outcomes of low-dose rivaroxaban combined with antiplatelet therapy (Rivaroxaban 2.5mg bid plus asprin or clopidogrel) and antiplatelet therapy alone (dual antiplatelet therapy or antiplatelet monotherapy) among patients with sICAS. The primary outcome was a composite of all-cause death, ischemic stroke or transient ischemic attack, and acute coronary syndrome within one year post-stroke. Propensity score matching was performed in a 1:3 ratio for the two groups of patients to mitigate confounders, adjusted hazard ratios (HR) were estimated using multivariate Cox regression model. The win-ratio method was employed to assess the composite outcome. Results: Among 1,308 patients, 123 (9.4%) were prescribed rivaroxaban and antiplatelet therapy. In the matched population, the primary endpoint event rate in this group was lower (11/123 [8.9%] vs. 63/369 [17.1%], P=0.029). Multivariate Cox regression analysis revealed a significant benefit from low-dose rivaroxaban (adjusted HR=0.459, 95% CI: 0.234-0.897, P=0.023). In addition, coronary heart disease (adjusted HR=1.674, 95% CI: 1.013-2.766, P=0.044) was identified as a risk factor associated with composite outcome during the 1-year follow-up. In the analysis of the hierarchical composite end point, the results for the primary end point favored rivaroxaban plus antiplatelet therapy (win ratio=1.948, 95% CI: 1.134-3.346, P=0.016). Conclusions: Low-dose rivaroxaban combined with antiplatelet therapy was superior to antiplatelet therapy alone for the prevention of all-cause death, recurrent stroke and acute coronary syndrome among patients with sICAS. These findings are preliminary and warrant further investigation through randomized controlled trials.

Prediction of obstructive coronary artery disease using coronary calcification and epicardial adipose tissue assessments from CT calcium scoring scans.

Low-cost/no-cost non-contrast CT calcium scoring (CTCS) exams can provide direct evidence of coronary atherosclerosis. In this study, using features from CTCS images, we developed a novel machine learning model to predict obstructive coronary artery disease (CAD), as defined by the coronary artery disease-reporting and data system (CAD-RADS). This study analyzed 1324 patients from the SCOT-HEART trial who underwent both CTCS and CT angiography. Obstructive CAD was defined as CAD-RADS 4A-5, while CAD-RADS 0-3 were considered non-obstructive CAD. We analyzed clinical, Agatston-score-derived, and epicardial fat-omics features to predict obstructive CAD. The most predictive features were selected using elastic net logistic regression and used to train a CatBoost model. Model performance was evaluated using 1000 repeated five-fold cross-validation and survival analyses to predict major adverse cardiovascular event (MACE) and revascularization. Generalizability was assessed using an external validation set of 2316 patients for survival predictions. Among the 1324 patients, obstructive CAD was identified in 334 patients (25.2​%). Elastic net regression identified the top 14 features (5 clinical, 2 Agatston-score-derived, and 7 fat-omics). The proposed method achieved excellent performance for classifying obstructive CAD, with an AUC of 90.1​±​0.9​% and sensitivity/specificity/accuracy of 83.5​±​5.5​%/93.7​±​1.9​%/82.4​±​2.0​%. The inclusion of Agatston-score-derived and fat-omics features significantly improved classification performance. Survival analyses showed that both actual and predicted obstructive CAD significantly differentiated patients who experienced MACE and revascularization. We developed a novel machine learning model to predict obstructive CAD from non-contrast CTCS scans. Our findings highlight the potential clinical benefits of CTCS imaging in identifying patients likely to benefit from advanced imaging.

Prognostic study of intracranial branch atheromatous disease in the blood-supplying areas of the lenticulostriate and paramedian pontine arteries.

Branch atheromatous disease (BAD) is prone to early neurological deterioration (END), leading to a poor prognosis. The most common arteries causing END are the lenticulostriate arteries (LSA) and the paramedian pontine arteries (PPA). To gain insight into the characteristics of symptomatic plaques and their association with poor prognosis in patients with BAD, we conducted a prospective study using high-resolution magnetic resonance imaging (HRMRI). A total of 75 patients with BAD in the vascular range of LSA or PPA were recruited for this study. The vascular and plaque features of the carrier middle cerebral artery (MCA) and basilar artery (BA) were evaluated through the application of HRMRI, and the local cerebral blood flow (CBF) of the lesion was assessed through pseudo-continuous arterial spin-labeling (pCASL), and the number and location of cerebral microbleeds (CMBs) were documented by susceptibility-weighted imaging (SWI). Univariable and multivariable logistic regression analyses were performed to analyze the factors that affected the prognosis. A poor prognosis was observed in 24 patients (32%) with BAD. A total of 28 patients (37%) developed END. Multifactorial analysis showed statistically significant differences in the dorsal plaque of BA (OR: 19.15, 95% CI 1.72-385.37, p=0.028), male (OR: 26.22, 95% CI 3.18-406.31, p=0.007), and NIHSS at 7 days of onset (OR: 2.24, 95% CI 1.4-4.45, p=0.004). In patients with BAD in LSA and PPA areas, the dorsal plaque of BA, male, and NIHSS at 7 days of onset were independent risk factors for poor prognosis.

Causal effects of circulating immune cells on coronary atherosclerosis: Evidence from Mendelian randomization.

The role of circulating immune cells in coronary atherosclerosis remains unclear. This study aimed to assess the causal effects of various immune cells on coronary atherosclerosis using Mendelian randomization (MR). Circulating immune cell datasets were obtained from genome-wide association studies, and coronary atherosclerosis datasets were obtained from FinnGen. Single-nucleotide polymorphisms satisfying the assumptions of association, independence, and exclusivity were screened in the datasets and analyzed using MR, with inverse-variance weighted as the main method. Horizontal pleiotropy, heterogeneity, and sensitivity analyses were performed using the MR-Egger, Cochran Q, and leave-one-out analyses, respectively. The MR analysis showed that effector memory double negative (DN) (cluster of differentiation [CD]4-CD8-) %DN (odds ratio [OR]: 1.042, 95% confidence interval [CI]: 1.008-1.077, P = .014), CD4 on CD39+ CD4+ (OR: 1.027, 95% CI: 1.001-1.054, P = .040), C-X3-C motif chemokine receptor 1 on CD14+ CD16- monocytes (OR: 1.035, 95% CI: 1.010-1.060, P = .006), C-C chemokine receptor 7 on naive CD4+ (OR: 1.035, 95% CI: 1.006-1.076, P = .023), and immunoglobulin D- CD38- %lymphocytes (OR: 1.098, 95% CI: 1.016-1.187, P = .019) were associated with an increased genetic susceptibility to coronary atherosclerosis, with no horizontal pleiotropy (P ≥ .05). Cochran Q showed no heterogeneity (P ≥ .05), and the sensitivity analysis indicated that the results were robust. The MR analysis revealed various markers and immune cell subsets, including effector memory DN (CD4-CD8-) %DN, CD4 on CD39+ CD4+, C-X3-C motif chemokine receptor on CD14+ CD16- monocytes, C-C chemokine receptor 7 on naive CD4+, and IgD- CD38- %lymphocytes, associated with increased genetic susceptibility to coronary atherosclerosis. This provides a genetic explanation for the role of specific immune cells in inducing and exacerbating coronary artery disease and offers new ideas for the exploration of immune markers and immune-targeted drugs.

Effects of LncRNA MYOSLID and MiR-29c-3p on the Proliferation and Migration of Angiotensin II-induced Vascular Smooth Muscle Cells

Atherosclerosis (ATH) represents a major cause of cardiovascular disease. Long noncoding RNA (LncRNA) myocardin-induced smooth muscle lncRNA, inducer of differentiation (MYOSLID) and microRNA (miR) -29c-3p show substantial roles in ATH. We investigated their regulatory mechanisms on vascular smooth muscle cell (VSMC) proliferation and migration.Angiotensin (Ang) II-induced VSMCs were used for in vitro research. The MYOSLID and miR-29c-3p expression patterns in VSMCs were assessed by reverse transcription-quantitative polymerase chain reaction. MYOSLID was overexpressed, or miR-29c-3p was silenced in VSMCs by cell transfection, followed by proliferation, migration, and apoptosis evaluation. The colocalization of MYOSLID and miR-29c-3p was observed by RNA in situ hybridization. The targeted binding relationship of miR-29c-3p and MYOSLID was verified by dual-luciferase and RNA immunoprecipitation assays. Joint experiments were performed with the overexpressed MYOSLID and miR-29c-3p via cotransfection. An ATH mouse model was established and injected with LV-MYOSLID, with the aortic root atherosclerotic lesion observed by HE staining and the α-SMA expression determined by immunohistochemistry.The MYOSLID expression was decreased, while the miR-29c-3p expression was increased in the Ang II-induced VSMCs, along with the promoted VSMC proliferation, apoptosis, and migration. Meanwhile, the MYOSLID overexpression or miR-29c-3p silencing repressed the Ang II-induced VSMC behaviors. The miR-29c-3p mimics reduced the luciferase activity of the MYOSLID 3'UTR-WT-transfected cells, but had no obvious influence on the MYOSLID 3'UTR-MUT-transfected cells. Overexpressed miR-29c-3p partially nullified the highly expressed MYOSLID-repressed Ang II-induced VSMC apoptosis, proliferation, and migration. The MYOSLID overexpression repressed the miR-29c-3p expression and reduced the atherosclerotic lesion area and the number of α-SMA-positive VSMCs in ATH mice.The MYOSLID overexpression restrained the Ang II-induced VSMC proliferation, migration, and apoptosis by repressing the miR-29c-3p expression, thus retarding the atherosclerotic plaque formation.

Noncardiac chest computerized tomography scan as a predictor for plaque presence in coronary artery.

Coronary artery calcium, a marker of coronary atherosclerosis, is often identified on noncoronary chest computed tomography (CT). We wanted to evaluate the correlation between the presence of coronary plaques in coronary artery catheterization and coronary calcifications as shown in noncardiac chest CT. A retrospective case-control study consisting of cases (N = 63) and controls (N = 29), aged 18-70 years old, residing in northern Israel and treated in the Intensive Cardiac Care Unit of Ziv Medical Center, between January 2020 and November 2022. All participants underwent coronary catheterization and noncoronary CT scans in the 5 years before the catheterization procedure. Data were taken from the participants' electronic files while considering the potential of cardiovascular risk factors. The 92 participants had a mean age of 60.1 ± 10.3 years old. Multivariate logistic regression adjusted to age, sex, and hyperlipidemia showed that calcified coronary artery as shown on a previous noncardiac CT scan was positively and significantly associated with increasing risk of coronary plaque as presented in coronary catheterization: odds ratio = 5.93 (95% confidence interval: 1.85-19.07, P < 0.01) and was also associated with male sex who were more likely to have plaque on coronary catheterization than females: odds ratio = 3.77 (95% confidence interval: 1.29-11.32, P < 0.05). Coronary calcifications on a previous noncoronary CT scan and sex are positively and significantly associated with coronary plaque risk as present in coronary catheterization. Coronary evaluation on CT scans is important for early detection of coronary disease. Early treatment can avoid coronary disease complications and increase patient survival.

Causal relationship between mental disorders and abdominal aortic aneurysm: Insights from the genetic perspective.

This study aims to investigate the genetic link between mental disorders-depression, schizophrenia (SCZ), and bipolar disorder (BIP)-and abdominal aortic aneurysm (AAA). We first examined the genetic associations between AAA and mental disorders by analyzing global and local genetic correlations as well as shared genomic loci. Global genetic correlation was assessed using linkage disequilibrium score regression (LDSC) and the GeNetic cOVariance Analyzer (GNOVA), while local genetic correlation was analyzed using the SUPERGNOVA approach. To identify shared genetic variants, the pleiotropy-informed conditional and conjunctional false discovery rate (pleioFDR) method was applied. Subsequently, the univariate Mendelian Randomization (UMR) was employed to evaluate the causal relationship, complemented by multivariate MR (MVMR) to account for potential confounding biases. Additionally, mediation analysis was performed to determine whether known risk factors mediate the identified causal relationships. Global correlations showed positive links between depression, SCZ, and AAA, but not BIP. Local analyses identified specific genomic regions of correlation. We found 26, 141, and 10 shared loci for AAA with depression, SCZ, and BIP, respectively. UMR indicated significant associations between genetically predicted depression (OR 1.270; 95 % CI 1.071-1.504; p = 0.006) and SCZ (OR 1.047; 95 % CI 1.010-1.084; p = 0.011) with AAA, but not BIP. These results were confirmed by MVMR analyses. Mediation analyses showed that smoking, hypertension, hyperlipidemia, and coronary atherosclerosis mediated the impact of depression on AAA while smoking mediated SCZ's impact. This study provides evidence that genetically predicted depression and SCZ are linked to an increased risk of AAA, mediated by traditional AAA risk factors.

PH-sensitive nano-drug delivery systems dual-target endothelial cells and macrophages for enhanced treatment of atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory disease characterized by vascular endothelial dysfunction. In the early stage of the disease, endothelial cell injury induces the infiltration of inflammatory macrophages, which secrete large amounts of inflammatory factors, further aggravating endothelial cell dysfunction and exacerbating the disease. Therefore, it is promising for co-targeting endothelial cells and macrophages further regulating the inflammatory microenvironment and endothelial cell function for effective treatment. The current nano-drug delivery system (NDDS) for AS treatment is mainly focused on anti-inflammatory therapy, while ignoring the potential value of suppressing inflammation and simultaneously improving vascular endothelial function. In this study, a pH-responsive dual-targeted NDDS based on plaque microenvironment, BC@CS/cRGD NPs, was prepared by combining baicalin (BC) with chondroitin sulfate (CS) through amidation reaction, and further modified with a targeting group cRGD peptide. In vitro release experiments illustrated a faster release of the nanoparticle at pH 5.0 than at pH 7.4. Meanwhile, in vitro cellular experiments demonstrated its ability to target activated endothelial cells and macrophages. In a mouse model of AS, BC@CS/cRGD NPs accumulated at plaque sites and effectively attenuated the plaque progression. In conclusion, this pH-sensitive BC@CS/cRGD NPs offered a very potential strategy for modulating endothelial dysfunction and inflammatory microenvironment for the treatment of AS.