Atherosclerotic Plaques In Coronary Arteries Research Articles

AGE-RAGE Stress and Coronary Artery Disease.

Coronary artery atherosclerosis and atherosclerotic plaque rupture cause coronary artery disease (CAD). Advanced glycation end products (AGE) and its cell receptor RAGE, and soluble receptor (sRAGE) and endogenous secretory RAGE (esRAGE) may be involved in the development of atherosclerosis. AGE and its interaction with RAGE are atherogenic, while sRAGE and esRAGE have antiatherogenic effects. AGE-RAGE stress is a ratio of AGE/sRAGE. A high AGE-RAGE stress results in development and progression of CAD and vice-versa. AGE levels in serum and skin, AGE/sRAGE in patients with CAD, and expression of RAGE in animal model of atherosclerosis were higher, while serum levels of esRAGE were lower in patients with CAD compared with controls. Serum levels of sRAGE in CAD patients were contradictory, increased or decreased. This contradictory data may be due to type of patients used, because the sRAGE levels are elevated in diabetics and end-stage renal disease. AGE/sRAGE ratio is elevated in patients with reduced or elevated levels of serum sRAGE. It is to stress that AGE, RAGE, sRAGE, or esRAGE individually cannot serve as universal biomarker. AGE and sRAGE should be measured simultaneously to assess the AGE-RAGE stress. The treatment of CAD should be targeted at reduction in AGE levels, prevention of AGE formation, degradation of AGE in vivo, suppression of RAGE expression, blockade of RAGE, elevation of sRAGE, and use of antioxidants. In conclusion, AGE-RAGE stress would initiate the development and progression of atherosclerosis. Treatment modalities would prevent, regress, and slow the progression of CAD.

Association of Epicardial Fat Volume With the Extent of Coronary Atherosclerosis and Cardiovascular Adverse Events in Asymptomatic Patients With Diabetes.

Epicardial adipose tissue has a paracrine effect, enhancing coronary artery atherosclerotic plaque development. This study evaluated epicardial fat volume (EFV), adipokines, coronary atherosclerosis, and adverse cardiovascular events in a cohort of asymptomatic patients with type 2 diabetes mellitus (T2DM). Epicardial fat volume was calculated using data from computed tomography coronary angiograms. Adipokines and inflammatory cytokines were also assayed and correlated with EFV. Epicardial fat volume was also assessed as a predictor of coronary artery calcium (CAC) score, number of coronary artery plaques, and significant plaque (>50% luminal stenosis). Data from the EFV analysis were available for 221 (85.7%) participants. Median EFV was 97.4 cm3, mean body mass index was 28.1 kg/m2, and mean duration of T2DM was 13 years. Statistically significant, but weak, correlations were observed between several adipokines, inflammatory cytokines, and EFV. Epicardial fat volume was a significant univariate (P = .01), but not multivariate, predictor of the number of coronary plaques, but not of CAC score or significant plaque. After a mean follow-up of 22.8 months, 12 adverse cardiovascular events were reported, exclusively in participants with EFV >97.4 cm3. Epicardial fat volume has limited utility as a marker of coronary artery plaque in patients with T2DM and is weakly correlated with adipokine expression.

Gene polymorphisms of hemostasis indices in men with coronary atherosclerosis

Background and Aims: The study was performed in the framework of the budget theme of the State assignment No. AAAA-A17-117112850280-2, the budget support bio-resource collections under State assignment No. 0324-2017-0048 and with the financial support of RFBR Grant No. 19-015-00055. Goal of research. To study polymorphisms of genes PAI-1, factor II, factor VII in order to find their associations with the presence of unstable atherosclerotic plaques in coronary arteries and with some clotting factors (factor II, factor VII, inhibitor of plasminogen activator-1, PAI-1).

Underperformance of clinical risk scores in identifying imaging-based high cardiovascular risk in psoriasis: results from two observational cohorts.

We aimed to evaluate whether traditional risk scores [short-term, 'psoriasis-modified' (multiplied by 1.5) and lifetime] were able to capture high cardiovascular disease (CVD) risk as defined by the presence of atherosclerotic plaques in coronary, femoral, or carotid arteries in psoriasis. We used two prospectives obseravational cohorts. European cohort: femoral and carotid atherosclerotic plaques were evaluated by ultrasound in 73 psoriasis patients. Lifetime CVD risk (LTCVR) was evaluated with QRISK-LT; short-term CVD risk was evaluated with SCORE and psoriasis-modified SCORE. American cohort: 165 patients underwent coronary computed tomography angiography to assess presence of coronary plaques. LTCVR was evaluated with atherosclerotic cardiovascular disease (ASCVD-LT) lifetime; short-term CVD risk was evaluated with ASCVD and psoriasis-modified ASCVD. European cohort: subclinical atherosclerosis was present in 51% of patients. QRISK-LT identified 64% of patients with atherosclerosis missing a high proportion (35%) with atheroma plaque (P < 0.05). The percentage of patients with atherosclerosis identified by QRISK-LT was significantly higher than those detected by SCORE (0%) and modified SCORE (10%). American cohort: subclinical atherosclerosis was present in 54% of patients. ASCVD-LT captured 54% of patients with coronary plaques missing a high proportion (46%) with coronary plaque (P < 0.05). The percentage of patients with atheroma plaques detected with ASCVD and modified ASCVD were only 20% and 45%, respectively. Application of lifetime, short-term and 'psoriasis-modified' risk scores did not accurately capture psoriasis patients at high CVD risk.

Single-Cell Genomics Reveals a Novel Cell State During Smooth Muscle Cell Phenotypic Switching and Potential Therapeutic Targets for Atherosclerosis in Mouse and Human.

Smooth muscle cells (SMCs) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration, and transdifferentiation into other cell types. Yet how SMCs contribute to the pathophysiology of atherosclerosis remains elusive. To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques. We also performed cell biology experiments on isolated SMC-derived cells, conducted integrative human genomics, and used pharmacological studies targeting SMC-derived cells both in vivo and in vitro. We found that SMCs transitioned to an intermediate cell state during atherosclerosis, which was also found in human atherosclerotic plaques of carotid and coronary arteries. SMC-derived intermediate cells, termed "SEM" cells (stem cell, endothelial cell, monocyte), were multipotent and could differentiate into macrophage-like and fibrochondrocyte-like cells, as well as return toward the SMC phenotype. Retinoic acid (RA) signaling was identified as a regulator of SMC to SEM cell transition, and RA signaling was dysregulated in symptomatic human atherosclerosis. Human genomics revealed enrichment of genome-wide association study signals for coronary artery disease in RA signaling target gene loci and correlation between coronary artery disease risk alleles and repressed expression of these genes. Activation of RA signaling by all-trans RA, an anticancer drug for acute promyelocytic leukemia, blocked SMC transition to SEM cells, reduced atherosclerotic burden, and promoted fibrous cap stability. Integration of cell-specific fate mapping, single-cell genomics, and human genetics adds novel insights into the complexity of SMC biology and reveals regulatory pathways for therapeutic targeting of SMC transitions in atherosclerotic cardiovascular disease.

Insight from imaging on plaque vulnerability: similarities and differences between coronary and carotid arteries-implications for systemic therapies.

Nowadays it is widely accepted that the rupture of the atherosclerotic plaque in coronary and carotid arteries plays a fundamental role in the development of acute myocardial infarctions or cerebrovascular events. In recent years, imaging techniques have explored, with a new level of detail, the atherosclerotic disease generating new evidences that some plaque characteristics are significantly associated to the risk of rupture and subsequent thrombosis or embolization. Moreover, the recent evidence of the anti-atherosclerotic effects determined by lipid-lowering and anti-inflammatory therapies poses a challenge for the choice of therapeutic approaches (best/optimal medical therapy vs. revascularization), maximized by the evidence that coronary and carotid atherosclerosis share common patterns but also differ regarding some important features. In this Review, we discuss the similarities and differences between coronary and carotid artery vulnerable plaque from the imaging point of view and the potential implications for systemic therapies according to the emerging evidence.

ST-Segment Elevation Myocardial Infarction with Normal Coronary Arteries Angiography

: Myocardial infarction (MI) is the most frequent cause of ischemic heart death. MI is generally assumed to be due to arterial thrombosis superimposed on an atherosclerotic plaque in an epicardial coronary artery. Total occlusion of an epicardial coronary artery leads to ST elevation, while non-occlusive lesion leads to ST depression. We hereby have reported a case of ST-segment elevation myocardial infarction with normal coronary arteries angiography. A 35-year-old man presented with typical chest pain, nausea, vomiting and cold sweating. ECG obtained at admission and 30 minutes later revealed sinus tachycardia with ST-segment elevations (&gt; 2 mm) in leads V2-V5. Cardiac biomarkers including creatine phosphokinase (CPK), creatine kinase muscle-brain (CK.MB) and troponin high sensitive were elevated. The standard treatment for MI including pain relief, aspirin, thrombolysis if indicated and beta blockade were begun for the patient. STEMI was confirmed and thus, angiography was performed. Coronary angiography revealed normal coronary arteries without any angiographic evidence of stenosis, coronary artery dissection, embolism, plaque rupture or vasospasm.

A Pathophysiologic Primary Prevention Review of Aspirin Administration to Prevent Cardiovascular Thrombosis

Cardiovascular disease is the leading metabolic cause of mortality in the United States. Among current therapies, low-dose aspirin has been shown to reduce cardiovascular thrombosis. However, aspirin also causes major complications (hemorrhagic stroke and gastrointestinal bleeding). The American Heart Association recommends that aspirin only be prescribed for "high-risk" individuals. No guidelines are available as to the duration of aspirin therapy. A reasonable approach to aspirin administration is to determine the appropriateness of aspirin therapy based on the pathophysiology of coronary artery thrombosis. It suggests that the coronary artery calcium (CAC) score be used as the basis for determining "high risk." This score was shown to accurately predict future cardiovascular events. The greater the CAC score, the greater the extent of coronary artery atherosclerotic plaque and future cardiovascular risk. A CAC score >400 places an individual at very-high 10-year risk for an atherosclerotic event. Since aggressive medical therapy initiates stabilization of unstable atherosclerotic plaques within 1 month and reversal within 2 years, this treatment significantly reduces the risk of the individual for a cardiovascular event. Thus, most individuals aged <75 years with a CAC score of >400 should receive aspirin therapy for a maximum of 2 years. Utilization of a CAC score greatly simplifies the decision of whom to treat with aspirin and for what duration. Importantly, focusing on two factors (hemorrhage and plaque stabilization) is easily understood by both the physician and the patient. CAC = coronary artery calcium; CVD = cardiovascular disease; LDL = low-density lipoprotein; OCT = optical coherence tomography.

Periodontal Inflammation and the Risk of Cardiovascular Disease.

The role of oral bacteremia and periodontal inflammation driving atherosclerosis is still under investigation. This review article highlights the role of periodontal inflammation and oral microorganisms in the development and progression of atherosclerosis and cardiovascular diseases. Association between periodontal and cardiovascular diseases has been well characterized, but causal correlation is yet to be established. For instance, untreated gingivitis can progress to periodontitis. Periodontal disease has been associated with several systemic diseases one of which is atherosclerosis. One possible association that was documented in literature is that poor oral hygiene leads to bacteremia, which in turn can cause bacterial growth over atherosclerotic coronary artery plaques and possibly worsen coronary artery disease. It is crucial that clinicians understand the association between periodontal and cardiovascular disease. A comprehensive treatment for periodontitis and re-establishment of a healthy periodontium can help in reduction of overall inflammation in the body. This may play an important role in prevention of cardiovascular disease, though future research is needed to establish this.

Comparative effectiveness of coronary artery stenosis and atherosclerotic plaque burden assessment for predicting 30-day revascularization and 2-year major adverse cardiac events

To provide comparative prognostic information of coronary atherosclerotic plaque volume and stenosis assessment in patients with suspected coronary artery disease (CAD). We followed 372 patients with suspected or known CAD enrolled in the CORE320 study for 2 years after baseline 320-detector row cardiac CT scanning and invasive quantitative coronary angiography (QCA). CT images were analyzed for coronary calcium scanning (CACS), semi-automatically derived total percent atheroma volume (PAV), segment stenosis score (SSS), in addition to traditional stenosis assessment (≥ 50%) by CT and QCA for (1) 30-day revascularization and (2) major adverse cardiac events (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare accuracy of risk prediction. Sixty percent of patients had obstructive CAD by QCA with 23% undergoing 30-day revascularization and 9% experiencing MACE at 2 years. Most late events (20/32) were revascularization procedures. Prediction of 30-day revascularization was modest (AUC range 0.67-0.78) but improved after excluding patients with known CAD (AUC range 0.73-0.86, p < 0.05 for all). Similarly, prediction of MACE improved after excluding patients with known CAD (AUC range 0.58-0.73 vs. 0.63-0.77). CT metrics of atherosclerosis burden performed overall similarly but stenosis assessment was superior for predicting 30-day revascularization. Angiographic and coronary atherosclerotic plaque metrics perform only modestly well for predicting 30-day revascularization and 2-year MACE in high risk patients but improve after excluding patients with known CAD. Atherosclerotic plaque metrics did not yield incremental value over stenosis assessment for predicting events that predominantly consisted of revascularization procedures. NCT00934037.

Exercise and Coronary Atherosclerosis: Observations, Explanations, Relevance, and Clinical Management.

Physical activity and exercise training are effective strategies for reducing the risk of cardiovascular events, but multiple studies have reported an increased prevalence of coronary atherosclerosis, usually measured as coronary artery calcification, among athletes who are middle-aged and older. Our review of the medical literature demonstrates that the prevalence of coronary artery calcification and atherosclerotic plaques, which are strong predictors for future cardiovascular morbidity and mortality, was higher in athletes compared with controls, and was higher in the most active athletes compared with less active athletes. However, analysis of plaque morphology revealed fewer mixed plaques and more often only calcified plaques among athletes, suggesting a more benign composition of atherosclerotic plaques. This review describes the effects of physical activity and exercise training on coronary atherosclerosis in athletes who are middle-aged and older and aims to contribute to the understanding of the potential adverse effects of the highest doses of exercise training on the coronary arteries. For this purpose, we will review the association between exercise and coronary atherosclerosis measured using computed tomography, discuss the potential underlying mechanisms for exercise-induced coronary atherosclerosis, determine the clinical relevance of coronary atherosclerosis in middle-aged athletes and describe strategies for the clinical management of athletes with coronary atherosclerosis to guide physicians in clinical decision making and treatment of athletes with elevated coronary artery calcification scores.

Quantification of atherosclerotic plaque volume in coronary arteries by computed tomographic angiography in subjects with and without diabetes.

BackgroundDiabetes mellitus (DM) is considered a cardiovascular risk factor. The aim of this study was to analyze the prevalence and volume of coronary artery plaque in patients with diabetes mellitus (DM) vs. those without DM.MethodsThis study recruited consecutive patients who underwent coronary computed tomography (CT) angiography (CCTA) between October 2016 and November 2017. Personal information including conventional cardiovascular risk factors was collected. Plaque phenotypes were automatically calculated for volume of different component. The volume of different plaque was compared between DM patients and those without DM.ResultsAmong 6381 patients, 931 (14.59%) were diagnosed with DM. The prevalence of plaque in DM subjects was higher compared with nondiabetic group significantly (48.34% vs. 33.01%, χ2 = 81.84, P < 0.001). DM was a significant risk factor for the prevalence of plaque in a multivariate model (odds ratio [OR] = 1.465, 95% CI: 1.258–1.706, P < 0.001). The volume of total plaque and any plaque subtypes in the DM subjects was greater than those in nondiabetic patients significantly (P < 0.001).ConclusionThe coronary artery atherosclerotic plaques were significantly higher in diabetic patients than those in non-diabetic patients.

Exploring the effects of free fatty acids in rat serum on the coronary atherosclerotic plaque formation by the CT projection measurement results of compression sensor

In order to investigate the effect of free fatty acids in serum on the formation of atherosclerotic plaque in coronary arteries, firstly, the atherosclerotic coronary artery rat model was constructed to detect the changes of body weight and body temperature in the control group and the experimental group. Then the serum of the rats was extracted to detect the difference of triglyceride, total cholesterol, fasting blood glucose, low density lipoprotein, high density lipoprotein, insulin and free fatty acid. The content differences of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids between the two groups were detected. Then, the difference of contents of serum NO, endothelin – 1 (ET-1), angiotensin II (AngII), ox-low-density lipoprotein (ox-LDL), interleukin-6 (IL-6) and tumor necrosis factor – α (TNF-α) in the rat model after 0 days of feeding and 150 days of feeding was detected by enzyme-linked immunosorbent assay. And the rat coronary artery tissue and myocardial histopathological sections were made for analysis. Finally, based on compression sensor technology, CT imaging results were used to analyze the effects of different fatty acid contents on the carotid intima-media thickness and arterial plaque in rats. The results showed that the weight, body temperature, triglyceride and other indexes in the experimental group were significantly higher than those in the control group at 150d (P < 0.05). The content of NO gene was significantly higher than that of the control group (P < 0.05). There were pathological injury, inflammation of coronary artery and myocardial tissue in the experimental group. The correlation analysis showed that the content of free fatty acids was correlated with carotid intima-media thickness and arterial plaque. Therefore, free fatty acids can be a risk factor for the formation of atherosclerotic plaque in coronary arteries.

Vulnerable atherosclerotic plaques of coronary arteries in patients with stable coronary artery disease: 12-months follow-up

A key objective of modern cardiology is the assessment of acute coronary syndrome (ACS) risk in patients with coronary artery disease (CAD) to develop preventive measures and choose optimal treatment strategies. Detect vulnerable plaques of non-target coronary arteries in patients with stable CAD during routine percutaneous coronary intervention using virtual-histology intravascular ultrasound (VH-IVUS) and view their morphology over time. The prospective observational cohort study included 58 patients with stable CAD. After stenting ofatarget vessel, VH-IVUS was carried out in proximal and middle segments (6-8 cm) of a non-target coronary artery with no significant stenosis according to coronary angiography. Twelve months later, all patients underwent coronary angiography with re-IVUS of previously detected lesions. Death, myocardial infarction, rehospitalization, and unplanned myocardial revascularization due to vulnerable plaques were the endpoints of the study. IVUS with virtual histology revealed 58 lesions of non-target coronary arteries in 56 (96.5 %) patients. Two patients had no lesions in non-target coronary arteries. A large necrotic core with thin cap (thin-cap fibroatheroma) was detected in 12 (20.7 %) plaques, six of which had additional ACS risk criteria (stenosis area &gt;70 % and / or lumen area &lt;4 mm2). Within the 12‑month follow-up period, three patients (one with a vulnerable plaque in IVUS) were hospitalized with a clinical picture of ACS. One cardiac death was registered in a patient with the IVUS vulnerable plaque. 7 of 12 vulnerable plaques stabilized in 12 months. 1) The data presented indicate a high rate (20.7 %) of vulnerable plaques of non-target coronary arteries in patients with stable CAD who underwent stenting; 2) Two (16.6 %) patients with vulnerable plaques reached endpoints (death and rehospitalization) within the 12‑month follow-up period; 3) An analysis ofatherosclerotic plaques in non-target coronary arteries over time showed that vulnerable plaques stabilized and did not cause ACS in more than half of cases (7 of 12); 4) Plaques that were not vulnerable according to IVUS were not likely to destabilize within the 12‑month follow-up period.

Coronary atherosclerosis in middle-aged athletes: Current insights, burning questions, and future perspectives.

Regular exercise training is considered healthy as it reduces the risk of cardiovascular events and mortality. Nevertheless, athletes are not immune to the development of cardiovascular diseases and recent studies reported a higher prevalence of coronary artery calcifications and atherosclerotic plaques in athletes compared to less active controls. These observations have raised many questions among sport scientists, sports cardiologists, amateur athletes, and the general population. For example, Are athletes (not) immune for coronary atherosclerosis? How to assess coronary atherosclerosis in athletes? What about chalk (calcified plaque) and cheese (mixed plaque)? Does exercise intensity play a role? Are there sport‐related differences? Are there sex differences? Can sports medical evaluation detect coronary atherosclerosis? Do athletes get worried? Should athletes get worried? How should athletes with coronary atherosclerosis be managed? The goal of this review is to discuss the latest scientific insights and to answer these important questions. Furthermore, we will explore potential clinical implications and point out directions for further research.

P197 Similarity and difference in in-stent neoatherosclerosis assessment between near-infrared spectroscopy and optical coherence tomography

Abstract Backgrounds Near-infrared spectroscopy (NIRS) has been implicated to assess the composition of the atherosclerotic plaques in native coronary arteries. However, little has been reported about the assessment of neoatherosclerosis within stents by NIRS. Optical coherence tomography (OCT) is one of the current clinical standard modalities to identify neoatherosclerosis. We sought to compare NIRS and OCT assessments in the detection and evaluation of in-stent neoatherosclerosis. Methods We retrospectively analyzed 54 in-stent lesions in 52 patients who underwent both NIRS and OCT examinations before percutaneous coronary intervention (PCI). All stented segment in both PCI target and non-target lesions were investigated. NIRS analysis included lipid core burden index (LCBI)4mm. NIRS-derived lipid-rich plaque (NIRS-lipid) is defined as LCBI4mm more than 400 according to the previous studies. OCT-derived lipid-laden neointima (OCT-lipid) was defined as having a signal-poor region with diffuse border precluding visualization of stent struts of more than 90 degrees and 1mm in longitudinal length. OCT analysis included the presence or absence of lipid-laden neointima, calcification, ruptured plaque, thrombus, heterogeneous neointima and measurement of lipid length and lipid arc. Lipid volume index (LVI) was defined by OCT as the averaged lipid arc multiplied by lipid length. Max LCBI4mm were compared in lesions with co-registered OCT findings and correlations between max LCBI4mm and LVI were determined. Additionally, OCT findings predicting max LCBI4mm more than 400 were determined. Results Max LCBI4mm was 202 (7.5-460). OCT-lipid was observed in 31 (57.4%) lesions. LVI was 1283 (475-4725). Lesions with OCT-lipid has significantly higher LCBI than those without OCT-lipid (343 [106-593] vs 42 [0-260], p = 0.003). On the other hand, max LCBI were not significantly different according to the presence or absence of calcification, ruptured plaque, thrombus and heterogeneous neointima (60 [39-537] vs 227 [6-451], p = 0.913; 441 [43-547] vs 202 [6-435], p = 0.328; 245 [10-548] vs 251 [42-446], p = 0.990; 202 [40-440] vs 235 [3-471], p = 0.970, respectively). Linear regression analysis showed significant correlation between LVI and max LCBI4mm (P &amp;lt; 0.001). Receiver operating characteristic (ROC) analysis showed the best cutoff max LCBI4mm value for predicting OCT-lipid was 148 (Area under the curve [AUC] = 0.735). ROC analysis showed the best cutoff lipid length and maximum lipid arch value for predicting LCBI4mm more than 400 was 1.9 mm and 128 degrees, (AUC = 0.741, 0.732, respectively) respectively. Conclusion There is good agreement between NIRS and OCT for detection of neoatherosclerosis in stented lesions. In the in-stent lesions, the cut-off value of max LCBI for predicting OCT-lipid was smaller than the previously reported value in de novo lesions. Application of different cut-off value may be considered in in-stent lesions.

The Role of Cardiac Ganglia in the Prevention of Coronary Atherosclerosis: An Analytical Examination of Cholesterol-fed Rabbits

Background:The heart is innervated by the autonomic nervous system, which contributes to the control of the heart’s rhythm and coronary circulation. It has been suggested that the cardiac fibers of the vagus nerve play important roles in controlling circulatory functions and in protecting against atherosclerotic pathologies in coronary arteries.Aims:To investigate the presence of atherosclerotic differences in the coronary arteries of cholesterol-fed rabbits by measuring the density of cardiac ganglia neurons.Study Design:Animal experiment.Methods:This study was conducted using 45 male rabbits. Over a period of 16 weeks, they were kept on an atherogenic diet of water ad libitum and high fat (8.6%) containing saturated fatty acids with 205 mg/kg of cholesterol (1%) per day. Then, their hearts were removed and examined by histopathological methods. Atherosclerotic plaques of the main coronary arteries were examined using the Cavalieri method. Atherosclerosis index values (AIVs) were estimated as the wall surface area/plaque surface area, and the results were analyzed with the Kruskal-Wallis and Mann-Whitney U tests.Results:While the average atherosclerosis index value was estimated to be ≤8% in 21 animals, the atherosclerosis index value was 9-20% in animals with minor plaque detection (n=11) and ≥20% in animals with major plaque detection (n=10). Increased atherosclerosis index values were more common in animals with low neuron densities than in animals with high neuron densities (p<0.017).Conclusion:The low neuron density of the cardiac ganglia in cholesterol-fed rabbits is associated with an increased atherosclerotic plaque incidence and volume.

A Proteomic Study of Atherosclerotic Plaques in Men with Coronary Atherosclerosis.

Background: To study the changes in protein composition of atherosclerotic plaques at different stages of their development in coronary atherosclerosis using proteomics. Methods: The object of research consisted of homogenates of atherosclerotic plaques from coronary arteries at different stages of development, obtained from 15 patients. Plaque proteins were separated by two-dimensional electrophoresis. The resultant protein spots were identified by the matrix-assisted laser desorption ionization method with peptide mass mapping. Results: Groups of differentially expressed proteins, in which the amounts of proteins differed more than twofold (p < 0.05), were identified in pools of homogenates of atherosclerotic plaques at three stages of development. The amounts of the following proteins were increased in stable atherosclerotic plaques at the stage of lipidosis and fibrosis: vimentin, tropomyosin β-chain, actin, keratin, tubulin β-chain, microfibril-associated glycoprotein 4, serum amyloid P-component, and annexin 5. In plaques at the stage of fibrosis and calcification, the amounts of mimecan and fibrinogen were increased. In unstable atherosclerotic plaque of the necrotic–dystrophic type, the amounts of human serum albumin, mimecan, fibrinogen, serum amyloid P-component and annexin were increased. Conclusion: This proteomic study identifies the proteins present in atherosclerotic plaques of coronary arteries by comparing their proteomes at three different stages of plaque development during coronary atherosclerosis.

The Blood Biomarkers Associated With Unstable Atherosclerotic Plaques In Patients With Coronary Atherosclerosis

Background and Aims: To determine blood biomarkers associated with unstable atherosclerotic plaques in coronary arteries.

The Human-Specific and Smooth Muscle Cell-Enriched LncRNA SMILR Promotes Proliferation by Regulating Mitotic CENPF mRNA and Drives Cell-Cycle Progression Which Can Be Targeted to Limit Vascular Remodeling.

In response to blood vessel wall injury, aberrant proliferation of vascular smooth muscle cells (SMCs) causes pathological remodeling. However, the controlling mechanisms are not completely understood. We recently showed that the human long noncoding RNA, SMILR, promotes vascular SMCs proliferation by a hitherto unknown mechanism. Here, we assess the therapeutic potential of SMILR inhibition and detail the molecular mechanism of action. We used deep RNA-sequencing of human saphenous vein SMCs stimulated with IL (interleukin)-1α and PDGF (platelet-derived growth factor)-BB with SMILR knockdown (siRNA) or overexpression (lentivirus), to identify SMILR-regulated genes. This revealed a SMILR-dependent network essential for cell cycle progression. In particular, we found using the fluorescent ubiquitination-based cell cycle indicator viral system that SMILR regulates the late mitotic phase of the cell cycle and cytokinesis with SMILR knockdown resulting in ≈10% increase in binucleated cells. SMILR pulldowns further revealed its potential molecular mechanism, which involves an interaction with the mRNA of the late mitotic protein CENPF (centromere protein F) and the regulatory Staufen1 RNA-binding protein. SMILR and this downstream axis were also found to be activated in the human ex vivo vein graft pathological model and in primary human coronary artery SMCs and atherosclerotic plaques obtained at carotid endarterectomy. Finally, to assess the therapeutic potential of SMILR, we used a novel siRNA approach in the ex vivo vein graft model (within the 30 minutes clinical time frame that would occur between harvest and implant) to assess the reduction of proliferation by EdU incorporation. SMILR knockdown led to a marked decrease in proliferation from ≈29% in controls to ≈5% with SMILR depletion. Collectively, we demonstrate that SMILR is a critical mediator of vascular SMC proliferation via direct regulation of mitotic progression. Our data further reveal a potential SMILR-targeting intervention to limit atherogenesis and adverse vascular remodeling.