Progression Of Atherosclerotic Disease Research Articles

An integrated e-health support of shared decision making and self-management (POWER2DM) for patients with diabetes mellitus and their healthcare professionals

Background and Aims : Diabetes mellitus accelerates the development and progression of atherosclerotic disease, especially when glucose levels are not well regulated. Several e-health systems aim to support patients in diabetes self-management (DSM), but lack to acknowledge its complexity. We developed and field-tested an e-health system integrating medical, psychological, and behavioral aspects and connected wearables to support patients and healthcare professionals in DSM (POWER2DM).

U-Shaped Relationship of Non-HDL Cholesterol With All-Cause and Cardiovascular Mortality in Men Without Statin Therapy.

BackgroundNon-HDL-C is well established causal risk factor for the progression of atherosclerotic cardiovascular disease. However, there remains a controversial pattern of how non-HDL-C relates to all-cause and cardiovascular mortality, and the concentration of non-HDL-C where the risk of mortality is lowest is not defined.MethodsA population-based cohort study using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Male participants without statin therapy were divided into the six groups according to non-HDL-C levels (<100, 100–129, 130–159, 160–189, 190–219, ≥220 mg/dl). Multivariable Cox proportional hazards models were conducted with a hazard ratio (HR) and corresponding 95% confidence interval (CI). To further explore the relationship between non-HDL-C and mortality, Kaplan–Meier survival curves, restricted cubic spline curves, and subgroup analysis were performed.ResultsAmong 12,574 individuals (average age 44.29 ± 16.37 years), 1,174(9.34%) deaths during a median follow-up 98.38 months. Both low and high non-HDL-C levels were significantly associated with increased risk of all-cause and cardiovascular mortality, indicating a U-shaped association. Threshold values were detected at 144 mg/dl for all-cause mortality and 142 mg/dl for cardiovascular mortality. Below the threshold, per 30 mg/dl increase in non-HDL-C reduced a 28 and 40% increased risk of all-cause (p < 0.0001) and cardiovascular mortality (p = 0.0037), respectively. Inversely, above the threshold, per 30 mg/dl increase in non-HDL-C accelerated risk of both all-cause mortality (HR 1.11, 95% CI 1.03–1.20, p = 0.0057) and cardiovascular mortality (HR 1.30, 95% CI 1.09–1.54, p = 0.0028).ConclusionsNon-HDL-C was U-shaped related to all-cause and cardiovascular mortality among men without statin therapy.

Altered Peroxisome Proliferator-Activated Receptor Alpha Signaling in Variably Diseased Peripheral Arterial Segments.

ObjectivePeripheral atherosclerosis that accumulates in the extracranial carotid and lower extremity arteries can lead to significant morbidity and mortality. However, atherosclerotic disease progression is often not homogenous and is accelerated by diabetes. We previously observed increased phospholipid content in minimally (Min)-diseased arterial segments compared to maximally (Max)-diseased segments. Since Peroxisome Proliferator-Activated Receptor alpha (PPARα) is a key regulator of lipid metabolism, we hypothesized that it may have differential expression and signaling in Min vs. Max-diseased peripheral arterial segments.MethodsEighteen patients who underwent carotid endarterectomy (CEA), and 34 patients who underwent major lower extremity amputation were prospectively enrolled into a vascular tissue biobank. Min and Max-diseased segments were obtained in real-time from CEA plaque and amputated lower extremity arterial segments. mRNA and protein were isolated from specimens and the relative expression of ppara, and its downstream genes Acyl-CoA Oxidase 1 (acox1) and Carnitine Palmitoyltransferase 1A (cpt1a) were also evaluated. We evaluated gene expression and protein content relative to atherosclerotic disease severity and clinical diabetes status. Gene expression was also evaluated relative to Hemoglobin A1c and serum lipid profiles.ResultsIn CEA segments of patients with diabetes, we observed significantly higher ppara and acox1 gene expression (p < 0.01 and p < 0.001 respectively), and higher PPARα protein content (p < 0.05). Hemoglobin A1c significantly correlated with expression of ppara (R2 = 0.66, p < 0.001), acox1 (R2 = 0.31, p < 0.05), and cpt1a (R2 = 0.4, p < 0.05). There was no significant difference in gene expression between Min vs. Max-diseased CEA plaque segments. Conversely, in lower extremity arterial segments of patients with diabetes, we observed significantly lower ppara, acox1, and cpt1a expression (p < 0.05, p < 0.001, and p < 0.0001 respectively). Interestingly, CPT1A content was lower in arterial segments of patients with diabetes (p < 0.05). Hemoglobin A1c and HDL-cholesterol had negative correlations with ppara (R2 = 0.44, p < 0.05; R2 = 0.42, p < 0.05; respectively).ConclusionThis study demonstrates the significant differential expression of ppara and its immediate downstream genes in human carotid and lower extremity arteries relative to disease severity and diabetes. These findings highlight that mechanisms that influence atheroprogression in the carotid and lower extremities peripheral arteries are not homogenous and can be impacted by patient diabetes status and serum cholesterol profiles. Further elucidating these differential molecular mechanisms can help improve targeted therapy of atherosclerosis in different peripheral arterial beds.

Impact of a comprehensive cardiac rehabilitation programme versus coronary revascularization in patients with stable angina pectoris: protocol for the PRO-FIT randomised controlled trial

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): ZonMW: The Netherlands Organisation for Health Research and Development Background Stable angina pectoris (SAP) is a highly common condition. Despite optimal medical treatment (OMT) patients often remain symptomatic and at high risk for cardiovascular morbidity and mortality. In daily practice the standard treatment consists of OMT usually followed by an invasive strategy, consisting of coronary angiography and subsequent coronary revascularization. However, recent studies showed that these costly and invasive procedures do not result in superior effects on re-events and prognosis as compared to drug therapy alone in patients with SAP. On the other hand, the effect of lifestyle-related interventions on vascular function and the progression of atherosclerotic coronary artery disease is well-known. Yet, contemporary RCTs comparing lifestyle interventions with coronary revascularization in patients with SAP are lacking. Purpose To compare the impact of a 12-month cardiac rehabilitation (CR) programme versus a routinely applied invasive approach (including coronary angiography and subsequent coronary revascularization) on anginal complaints and cost-effectiveness in SAP patients. We hypothesize that CR is at least equally effective as an invasive approach. Methods 216 SAP patients with residual anginal complaints under OMT will be randomized to usual care or a 12-month CR intervention aiming at angina relief and sustainable behavioural change for long-lasting improvement in cardiovascular health. The CR programme consists of multiple lifestyle interventions including an exercise programme, a dietary intervention and a psychoeducation module with a stepped decline in guidance by health care professionals. Patients in the CR group will receive access to an online platform, a chatbot and a smartwatch enabling patients and professionals to monitor the progress and adherence to lifestyle advices. During the first 3 months patients will receive face to face guidance, the next 3 months will consist of telerehabilitation using the smartwatch with weekly video consulting and the last 6 months will be focussed on relapse prevention and guidance on demand. The primary outcome will be the quantity of anginal complaints (evaluated by the Seattle Angina Questionnaire-7) following the 12-month intervention. Secondary outcomes include cost-effectiveness, the ischemic threshold during exercise, cardiovascular events, exercise capacity, quality of life and psychosocial wellbeing. Future implications This will be the first study evaluating a comprehensive disease-specific multimodal lifestyle intervention as a primary treatment for patients with SAP. If proven successful this study will have a great impact on the daily care of these patients as coronary revascularizations can partly be replaced by a less invasive, less costly and better sustainable treatment.

Baseline carotid intima-media complex echogenicity associates with the 3-year progression of intima-media thickness

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Region Vasterbotten Central ALF and the Swedish Research Council Background Echogenicity of the intima-media (IM) complex and progression of carotid intima media thickness (cIMT) have both separately been demonstrated to predict cardiovascular disease (CVD). However, it is unknown if the IM echogenicity reflects arterial wall remodelling associated with increased progression of cIMT. Purpose The aim of this study was to evaluate if the baseline echogenicity of the IM-complex measured by ultrasound is associated with cIMT progression over a 3-year follow-up period. Methods Ultrasound images from baseline and 3-year follow-up performed for the randomised controlled trial ‘Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention’ (VIPVIZA) were included in this study (n: 3154). Participants were 40, 50 or 60 years old at baseline and had at minimum one traditional risk factor for CVD to be included in the VIPVIZA study. Measurements of mean cIMT were made at baseline and in the 3-year follow-up in the distal 1 cm of the common carotid artery at standardised angles bilaterally. Echogenicity of the IM-complex was determined by greyscale median (IM-GSM), automatically calculated from the B-mode ultrasound images. Associations between IM-GSM at baseline and the 3-year progression of cIMT were investigated using linear regression models, and stratified by sex, age and VIPVIZA study group (intervention versus control). In addition, adjusted analysis for traditional risk factors was also performed. All analysis was carried out on left and right sides separately. Results The unadjusted analysis showed associations between baseline IM-GSM with the 3-year progression of cIMT (p&amp;lt;0.001 for both left and right sides, Figure 1). The association between IM-GSM and cIMT was statistically significant bilaterally in both male and female participants and on comparison of VIPVIZA study subgroups. When stratifying by age group, the association between baseline IM-GSM and cIMT progression was present among 40 (p&amp;lt;0.001) and 60 year olds (p&amp;lt;0.001), but not among 50 years old (p=0.906) in the left side. In the right CCA the association was significant among 40 years old (p=0.047), but not for 50 and 60 years (p=0.106 and 0.067, respectively). Adjustments for traditional risk factors did not alter the estimated relationship between baseline IM-GSM and 3-year cIMT progression. Conclusion Baseline ultrasound echogenicity of the IM-complex is associated with the 3-year progression of cIMT among a middle-aged population with subclinical atherosclerosis. Echogenicity of the IM-complex may serve to identify arterial wall remodelling reflecting progressive atherosclerotic disease and could be a valuable tool in future CVD prevention.

Through the layers: how macrophages drive atherosclerosis across the vessel wall.

Cardiovascular disease (CVD) accounts for almost half of all deaths related to non-communicable disease worldwide, making it the single largest global cause of mortality. Although the risk factors for coronary artery disease — the most common cause of CVD — are well known and include hypertension, high cholesterol, age, and genetics, CVDs are now recognized as chronic inflammatory conditions. Arterial blockages, known as atherosclerosis, develop due to excess cholesterol accumulating within the arterial wall, creating a perpetually inflammatory state. The normally quiescent intimal layer of the vessel wall becomes laden with inflammatory cells, which alters the surrounding endothelial, smooth muscle, and extracellular matrix components to propagate disease. Macrophages, which can be either tissue resident or monocyte derived, are a key player in atherosclerotic disease progression and regression, and the understanding of their functions and origins continues to evolve with the use of deep phenotyping methodologies. This Review outlines how macrophages interact with each layer of the developing atherosclerotic plaque and discusses new concepts that are challenging our previous views on how macrophages function and our evolving understanding of the contribution of macrophages to disease.

Abstract 245: Antibody Responses To ApoA-I Rely On An Interplay Between B And T Cells

Apolipoprotein A-I (ApoA-I), the major protein of high-density lipoprotein (HDL), has been investigated as the target and regulatory element of immune responses in both patients and mice susceptible to atherosclerosis. Previous work by our lab has focused on investigating the immune responses to ApoA-I in wild-type mice as a strategy to understand their role in models of atherosclerosis and other inflammatory conditions. We hypothesize that peripheral immunologic tolerance is responsible for regulating the dynamic immune response to ApoA-I. To examine this, we first evaluated antibody profiles to ApoA-I in both wild-type C57BL/6 and LDL receptor knockout mice and found that anti-ApoA-I antibodies naturally develop to the protein. To determine whether this response was T cell dependent or independent, we examined whether nu/nu mice on a BALB/c background, and the parent strain, displayed the phenotype. These studies showed that both nu/nu, or wild type BALB/c mice fail to mount antibody responses to ApoA-I suggesting a regulatory mechanism might be responsible for suppressing this antibody response. Ex vivo stimulation of immune cells with ApoA-I provide evidence of both B cell and T cell activation, suggesting that peripheral tolerance mechanisms may be responsible for regulating the humoral and cellular immune response to ApoA-I. These findings agree with previous studies where ApoA-I has been shown to regulate T cell activity in the context of atherosclerosis by inducing the development of regulatory T cells, which assist in suppressing the development of plaque formation; as well as studies showing a higher propensity toward Treg development in BALB/c mice. Ongoing experiments, which more clearly characterize the role of B cells and T cells in response to ApoA-I, will be presented with the goal of clarifying the immune mechanisms responsible for anti-ApoA-I autoimmunity. These data will help guide continued understanding of the role of immune responses to ApoA-I in atherosclerotic disease progression.

Abstract 542: Race, Sex, And Age Differences In Peripheral Arterial Disease-related Mortality In The United States, 2000 To 2019

Introduction: Peripheral arterial disease (PAD) is a progressive atherosclerotic disease associated with significant morbidity and mortality in the US, however, data regarding mortality trends is limited. This study uses national death certificate data to characterize contemporary trends in PAD-related mortality in the US. Methods: The Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) was queried for data regarding PAD-related deaths from 2000 to 2019 in the overall sample and from different demographics (age, sex, race). Crude and age-adjusted mortality rates (AAMR) per 100,000 people were calculated. Associated average percentage changes (APC) were computed using Joinpoint trend analysis software. Results: Between 2000 and 2019, a total of 1,959,050 PAD-related deaths occurred in the study population. Overall, AAMR decreased from 2000 to 2016, but remained relatively the same between 2016 to 2019. Men, Non-Hispanic (NH) Black or African American, NH American Indian or Alaska Native, and NH Asian or Pacific Islander showed a decline in AAMR. Women, NH White, Hispanic or Latino, ages 55 to 69 years, and 70 to 84 years showed initial declines, with no change in recent years. Ages 40 to 54 only had a change in crude mortality between 2002 and 2010. Overall, men, NH Black or African American individuals, and people aged 85+ were associated with the highest AAMRs of their respective subgroups throughout the study period. Notably, there was an increase in crude mortality rate amongst individuals 25-39 years of age from 2009 to 2019. Conclusion: PAD-related mortality in the US decreased from 2000 to 2016 but has stabilized in recent years. Despite improvement, disparities amongst sex, race, and age remain. Figure 1. PAD-related mortality rates by 1.A. sex 1.B. race 1.C. ages 25-54 and 1.D. ages 55-85+ in the United States, 2000 to 2019. *Indicates that APC is significantly different from zero at α=0.05.

New Treatment Targets and Innovative Lipid-Lowering Therapies in Very-High-Risk Patients with Cardiovascular Disease.

The effective and fast reduction of circulating low-density lipoprotein cholesterol (LDL-C) is a cornerstone for secondary prevention of atherosclerotic disease progression. Despite the substantial lipid-lowering effects of the established treatment option with statins and ezetimibe, a significant proportion of very-high-risk patients with cardiovascular disease do not reach the recommended treatment goal of <55 mg/dL (<1.4 mmol/L). Novel lipid-lowering agents, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies alirocumab and evolocumab, the small interfering ribonucleotide acid (si-RNA) inclisiran, as well as the recently approved bempedoic acid, now complete the current arsenal of LDL-C lowering agents. These innovative therapies have demonstrated promising results in clinical studies. Besides a strong reduction of LDL-C by use of highly effective agents, there is still discussion as to whether a very rapid achievement of the treatment goal should be a new strategic approach in lipid-lowering therapy. In this review, we summarize evidence for the lipid-modifying properties of these novel agents and their safety profiles, and discuss their potential pleiotropic effects beyond LDL-C reduction (if any) as well as their effects on clinical endpoints as cardiovascular mortality. In addition to a treatment strategy of “the lower, the better”, we also discuss the concept of “the earlier, the better”, which may also add to the early clinical benefit of large LDL-C reduction after an acute ischemic event.

Major adverse limb events in patients with femoro-popliteal and below-the-knee peripheral arterial disease treated with either sirolimus-coated balloon or standard uncoated balloon angioplasty: a structured protocol summary of the \u201cSirPAD\u201d randomized controlled trial

BackgroundPeripheral arterial disease is a progressive atherosclerotic disease with symptoms ranging from an intermittent claudication to acute critical limb ischemia and amputations. Drug-coated balloons and stents were developed to prevent neo-intimal proliferation and restenosis after percutaneous transluminal angioplasty. Randomized controlled trials showed that drug-coated, notably paclitaxel-coated, devices reduce restenosis, late lumen loss, and the need for target lesion re-vascularization compared with uncoated ones. However, the size of these trials was too small to prove superiority for “hard” clinical outcomes. Moreover, available studies were characterized by too restrictive eligibility criteria. Finally, it remains unclear whether paclitaxel-coated balloons may impair long-term survival. Alternative drug-coated balloons, the so-called limus-based analogs, have been approved for clinical use in patients with peripheral arterial disease. By encapsulating sirolimus in phospholipid drug nanocarriers, they optimize adhesion properties of sirolimus and provide better bioavailability.MethodsIn this investigator-initiated all-comer open-label phase III randomized controlled trial, we will evaluate whether sirolimus-coated balloon angioplasty is non-inferior and eventually superior, according to a predefined hierarchical analysis, to uncoated balloon angioplasty in adults with infra-inguinal peripheral arterial disease requiring endovascular angioplasty. Key exclusion criteria are pregnancy or breastfeeding, known intolerance or allergy to sirolimus, and participation in a clinical trial during the previous 3 months. The primary efficacy outcome is the composite of two clinically relevant non-subjective “hard” outcomes: unplanned major amputation of the target limb and endovascular or surgical target lesion re-vascularization for critical limb ischemia occurring within 1 year of randomization. The primary safety outcome includes death from all causes.DiscussionBy focusing on clinically relevant outcomes, this study will provide useful information on the efficacy and safety of sirolimus-coated balloon catheters for infra-inguinal peripheral arterial disease in a representative (“all-comer”) population of unselected patients. As regulatory agencies had raised safety concerns in patients exposed to paclitaxel-coated devices (versus uncoated ones), collect mortality data up to 5 years after randomization will be collected.Trial registrationClinicalTrials.govNCT04238546

Pressure and stiffness sensing together regulate vascular smooth muscle cell phenotype switching.

Vascular smooth muscle cells (VSMCs) play a central role in the progression of atherosclerosis, where they switch from a contractile to a synthetic phenotype. Because of their role as risk factors for atherosclerosis, we sought here to systematically study the impact of matrix stiffness and (hemodynamic) pressure on VSMCs. Thereby, we find that pressure and stiffness individually affect the VSMC phenotype. However, only the combination of hypertensive pressure and matrix compliance, and as such mechanical stimuli that are prevalent during atherosclerosis, leads to a full phenotypic switch including the formation of matrix-degrading podosomes. We further analyze the molecular mechanism in stiffness and pressure sensing and identify a regulation through different but overlapping pathways culminating in the regulation of the actin cytoskeleton through cofilin. Together, our data show how different pathological mechanical signals combined but through distinct pathways accelerate a phenotypic switch that will ultimately contribute to atherosclerotic disease progression.

Lipid-lowering for the prevention of cardiovascular disease in the new era: A practical approach to combination therapy: Lipid-lowering and combination therapy

Low density lipoprotein-cholesterol (LDL-C) is the main etiologic factor for the development and progression of atherosclerotic cardiovascular disease (ASCVD) and LDL-C reduction is a central tenet of ASCVD treatment and prevention. Moreover, ASCVD risk reduction is proportional to the magnitude of LDL-C lowering. Recent European guidelines have recommended a goal of &lt;55 mg/dL (&lt;1.4 mmol/L) for patients at very-high cardiovascular risk, while the U.S. guideline considers an LDL-C ≥70 mg/dL (≤1.8 mmol/L) as a threshold to intensify therapy with the addition of a non-statin therapy to statins. To reach these lower LDL-C goals of &lt;55 mg/dL or &lt;70 mg/dL, combination therapy is necessary in the majority of these patients. Drug combinations, and in particular single-pill combinations, may substantially increase adherence to therapy. Adherence is essential for achieving a clinical benefit and, as many patients discontinue medications, the long-term adherence to lipid-lowering therapy represents a major issue in ASCVD prevention. Secondary prevention or high-risk primary prevention patients, such as those with familial hypercholesterolemia in whom maximally-tolerated statin doses alone would not be anticipated to sufficiently lower LDL-C, would benefit from combination therapy. In current clinical practice, statins with ezetimibe, statins plus PCSK9 inhibitors (with or without ezetimibe), and, most recently statins or ezetimibe with bempedoic acid are the most commonly used combination therapies for LDL-C-lowering. This review outlines the importance of using combination therapy for the achievement of LDL-C treatment

Targeting Cell-Specific Molecular Mechanisms of Innate Immunity in Atherosclerosis.

Mechanisms of innate immunity contribute to inflammation, one of the major underlying causes of atherogenesis and progression of atherosclerotic vessel disease. How immune cells exactly contribute to atherosclerosis and interact with molecules of cholesterol homeostasis is still a matter of intense research. Recent evidence has proposed a potential role of previously underappreciated cell types in this chronic disease including platelets and dendritic cells (DCs). The pathophysiology of atherosclerosis is studied in models with dysfunctional lipid homeostasis and several druggable molecular targets are derived from these models. Specific therapeutic approaches focussing on these immune mechanisms, however, have not been successfully introduced into everyday clinical practice, yet. This review highlights molecular insights into immune processes related to atherosclerosis and potential future translational approaches targeting these molecular mechanisms.

Role of C - Reactive Protein as an Inflammatory Marker in Patients with Coronary Artery Disease: A Case – Control Study in Erbil- Kurdistan Region of Iraq

Background and aim: Inflammation has been long regarded as a key contributor to atherosclerosis. Recent decades have provided extensive and mounting evidence concerning the pivotal interplay between inflammation and CAD, reinforcing the concept of inflammation not only as a risk marker but also as a risk factor for the development and progression of atherosclerotic disease. Methods: This was a case control study that has been enrolled among 404 patients, divided into two different groups (case-CAD patients and control group-Patients with Normal Coronary Angiography) that presented to Catheterization unit of Surgical Specialty Hospital- Cardiac Center/ Erbil City-Iraq from 1 Sept 2021 to 1 Jan 2022. Results: A total of 404 patients of case and control group was included from both genders, the mean age was 55.9 ±10.6, ranging from 30 to 77 years of age, based on their coronary angiographic profile 57.4% of them were Coronary Artery Disease cases and 42.6% were controls. (58.4%) of the study population were males and (41.6%) were females. The mean of CRP level amongst cases were higher (6.2 ± 10) than the controls (3.5 ± 4.7), and this was significant with a P = 0.022. In our study we found that Highly Sensitive-CRP was high amongst Case Group (Patients with CAD) by 70% while comparing to only 30% of Control group who had High CRP levels. And this was statistically significant with a P value of 0.003. Conclusion: The level of CRP was higher among patients with Coronary Artery Disease, than those with Normal Coronary Angiography. The level was higher among.

LINC00460 Stimulates the Proliferation of Vascular Endothelial Cells by Downregulating miRNA-24-3p.

Objective To clarify the effect of LINC00460 on mediating the proliferative ability of vascular endothelial cells (ECs) by targeting microRNA-24-3p (miRNA-24-3p), thus influencing the progression of atherosclerotic diseases. Methods Relative levels of LINC00460 and miRNA-24-3p in ECs induced with different doses of ox-LDL (oxidized low density lipoprotein) for different time points were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Influences of LINC00460 and miRNA-24-3p on the viability of ECs were assessed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assay. Through dual-luciferase reporter gene assay, the binding between LINC00460 and miRNA-24-3p was evaluated. At last, rescue experiments were performed to identify the function of the LINC00460/miRNA-24-3p axis in regulating the proliferative ability of ECs. Results LINC00460 was upregulated after ox-LDL treatment in a dose- and time-dependent manner. Viability of ECs gradually increased with the prolongation of ox-LDL treatment and the treatment of increased dose. The overexpression of LINC00460 enhanced the viability and EdU-positive rate in ECs treated with ox-LDL. miRNA-24-3p was the direct target of LINC00460, which was negatively regulated by LINC00460. miRNA-24-3p was downregulated with the prolongation of ox-LDL treatment. The overexpression of miRNA-24-3p could reverse the effect of LINC00460 on regulating the proliferative ability of ECs. Conclusions LINC00460 regulates the proliferative ability of ECs and thus the occurrence and development of coronary atherosclerotic diseases by targeting miRNA-24-3p.

False Utopia of One Unifying Description of the Vulnerable Atherosclerotic Plaque: A Call for Recalibration That Appreciates the Diversity of Mechanisms Leading to Atherosclerotic Disease.

Atherosclerosis is a complex disease characterized by the formation of arterial plaques with a broad diversity of morphological phenotypic presentations. Researchers often apply one description of the vulnerable plaque as a gold standard in preclinical and clinical research that could be applied as a surrogate measure of a successful therapeutic intervention, despite the variability in lesion characteristics that may underly a thrombotic occlusion. The complex mechanistic interplay underlying progression of atherosclerotic disease is a consequence of the broad range of determinants such as sex, risk factors, hemodynamics, medications, and the genetic landscape. Currently, we are facing an overwhelming amount of data based on genetic, transcriptomic, proteomic, and metabolomic studies that all point to heterogeneous molecular profiles of atherosclerotic lesions that lead to a myocardial infarction or stroke. The observed molecular diversity implies that one unifying model cannot fully recapitulate the natural history of atherosclerosis. Despite emerging data obtained from -omics studies, a description of a natural history of atherosclerotic disease in which cell-specific expression of proteins or genes are included is still lacking. This also applies to the insights provided by genome-wide association studies. This review will critically discuss the dogma that the progression of atherosclerotic disease can be captured in one unifying natural history model of atherosclerosis.

Cathepsin S are involved in human carotid atherosclerotic disease progression, mainly by mediating phagosomes: bioinformatics and in vivo and vitro experiments.

BackgroundAtherosclerosis emerges as a result of multiple dynamic cell processes including endothelial damage, inflammatory and immune cell infiltration, foam cell formation, plaque rupture, and thrombosis. Animal experiments have indicated that cathepsins (CTSs) mediate the antigen transmission and inflammatory response involved in the atherosclerosis process, but the specific signal pathways and target cells of the CTSs involved in atherosclerosis are unknown.MethodsWe used the GEO query package to download the dataset GSE28829 from the Gene Expression Omnibus (GEO) and filtered the data to check the standardization of the samples through the box chart. We then used the ‘limma’ package to analyze between-group differences and selected the corresponding differentially expressed genes of CTSs from the protein-protein interaction (PPI) network constructed with the STRING database, and then visualized the CTS-target genes. The best matching pathway and target cells were verified by a male mouse ligation experiment, single-sample GSEA (ssGSEA) analysis, and vitro experiment.ResultsThere were 275 differentially expressed genes (DEGs) selected from the GSE28829 dataset, and the DEGs were identified mainly in the PPI network; 58 core genes (APOE, CD74, CP, AIF1, etc.) target three selected CTS family members (CTSS, CTSB, and CTSC). After the enriched analysis, 15 CTS-target genes were markedly enriched in the phagosome signaling pathway. The mouse experiment results revealed that the percentages and numbers of monocytes and neutrophils and the number of CD68+ cells in CTSS deficiency (CatS−/−) group were lower than those in the wildtype (CatS+/+) group. CTSS mediating phagosome via macrophage were further verified by ssGSEA analysis and vitro experiment.ConclusionsCTSS are the main target molecules in the CTS family that are involved in atherosclerosis. The molecule participate in the progression of atherosclerosis by mediating the phagosome via macrophage.

Arterial stiffness in rheumatoid arthritis: Current knowledge and future perspectivess

Rheumatoid arthritis (RA) is characterized by the excess cardiovascular risk that remains essentially unaltered despite current medical advances. The introduction of reliable markers towards early identification and subsequently effective management of high-risk patients with RA are urgently needed. Arterial stiffness represents an early indicator of cardiovascular morbidity and mortality and has emerged as a surrogate marker of cardiovascular disease. From a pathophysiological perspective, it is significantly accelerated by the accumulation of cardiovascular risk factors and is considered an intermediate process towards the development and progression of atherosclerotic cardiovascular disease. The aim of this review is to critically upraise current knowledge on arterial stiffness in patients with RA. Although not all studies concur, increased Pulse Wave Velocity (PWV) has been repeatedly reported in patients with RA. However, results need to be interpreted with caution as most studies enrolled patients with multiple cardiovascular risk factors and/or established cardiovascular disease, or with uncontrolled RA with high levels of systemic inflammation. Whether and to which extent increased arterial stiffness among patients with RA is associated with the disease per se, or rather represents the composite effect of hypertension and other classical cardiovascular risk factors, warrants further investigation. The impact of antirheumatic drugs on arterial stiffness is also discussed. Considering the well-established predictive value of increased PWV both in the general population and patients at high cardiovascular risk, future studies need to focus on the clinical utility of this surrogate risk marker specifically in patients with RA.

Error Propagation in the Simulation of Atherosclerotic Plaque Growth and the Prediction of Atherosclerotic Disease Progression.

Assessments of coronary artery disease can be achieved using non-invasive computed tomography coronary angiography (CTCA). CTCA can be further used for the 3D reconstruction of the coronary arteries and the development of computational models. However, image acquisition and arterial reconstruction introduce an error which can be propagated, affecting the computational results and the accuracy of diagnostic and prognostic models. In this work, we investigate the effect of an imaging error, propagated to a diagnostic index calculated using computational modelling of blood flow and then to prognostic models based on plaque growth modelling or binary logistic predictive modelling. The analysis was performed utilizing data from 20 patients collected at two time points with interscan period of six years. The collected data includes clinical and risk factors, biological and biohumoral data, and CTCA imaging. The results demonstrated that the error propagated and may have significantly affected some of the final outcomes. The calculated propagated error seemed to be minor for shear stress, but was major for some variables of the plaque growth model. In parallel, in the current analysis SmartFFR was not considerably affected, with the limitation of only one case located into the gray zone.

Ultrasound deep learning for monitoring of flow–vessel dynamics in murine carotid artery

Several arterial diseases are closely related with mechanical properties of the blood vessel and interactions of flow–vessel dynamics such as mean flow velocity, wall shear stress (WSS) and vascular strain. However, there is an opportunity to improve the measurement accuracy of vascular properties and hemodynamics by adopting deep learning-based ultrasound imaging for flow–vessel dynamics (DL-UFV). In this study, the DL-UFV is proposed by devising an integrated neural network for super-resolved localization and vessel wall segmentation, and it is also combined with tissue motion estimation and flow measurement techniques such as speckle image velocimetry and speckle tracking velocimetry for measuring velocity field information of blood flow. Performance of the DL-UFV is verified by comparing with other conventional techniques in tissue-mimicking phantoms. After the performance verification, in vivo feasibility is demonstrated in the murine carotid artery with different pathologies: aging and diabetes mellitus (DM). The mutual comparison of flow–vessel dynamics and histological analyses shows correlations between the immunoreactive region and abnormal flow–vessel dynamics interactions. The DL-UFV improves biases in measurements of velocity, WSS, and strain with up to 4.6-fold, 15.1-fold, and 22.2-fold in the tissue-mimicking phantom, respectively. Mean flow velocities and WSS values of the DM group decrease by 30% and 20% of those of the control group, respectively. Mean flow velocities and WSS values of the aging group (34.11 cm/s and 13.17 dyne/cm2) are slightly smaller than those of the control group (36.22 cm/s and 14.25 dyne/cm2). However, the strain values of the aging and DM groups are much smaller than those of the control group (p < 0.05). This study shows that the DL-UFV performs better than the conventional ultrasound-based flow and strain measurement techniques for measuring vascular stiffness and complicated flow–vessel dynamics. Furthermore, the DL-UFV demonstrates its excellent performance in the analysis of the hemodynamic and hemorheological effects of DM and aging on the flow and vascular characteristics. This work provides useful hemodynamic information, including mean flow velocity, WSS and strain with high-resolution for diagnosing the pathogenesis of arterial diseases. This information can be used for monitoring progression and regression of atherosclerotic diseases in clinical practice.