Progression Of Atherosclerotic Lesions Research Articles

Ethereal Extract of Pepper: Preventing Atherosclerosis and Left Ventricle Remodeling in LDL Receptor Knockout Mice.

Cardiovascular diseases are the leading cause of mortality and morbidity worldwide. In this study we compared the effects of oral treatment with red pepper ethereal extracts or simvastatin on dyslipidemia, left ventricle remodeling, and atherosclerotic lesions of low-density lipoprotein (LDL) receptor knockout mice (LDLr−/−) fed a hyperlipidic diet. Forty 3-month-old male mice were distributed into four groups: control (C; animals fed a standard diet), HL (ani-mals fed a hyperlipidic diet), and HL+P or HL+S (animals fed a hyperlipidic diet plus red pepper ethereal extracts or simvastatin, respectively). After 60 days, treatment with both red pepper ethereal extracts and simvastatin prevented dyslipidemia, atherosclerotic lesion progression, and left ventricle hypertrophy. Our results suggest a cardioprotective effect of red pepper ethereal extracts in LDLr−/− mice, which is comparable to the well-known effects of simvastatin.

Study of Diagnostic Value of Cyclooxygenase-2 and Matrix Metalloproteinases in Atherosclerosis

Background and Aim: Atherosclerosis is a chronic systematic disease where lesion (plaque) develops results in activation of inflammatory reaction that leads to arterial obstruction. Atherosclerosis is the underlying cause for many cardiovascular diseases (CVD) which were estimated with 42 percent of total death in Saudi Arabia while Coronary artery diseases (CAD) accounted for 35 percent of total chronic diseases death in Saudi Arabia by 2008. Risk factors that attribute in progression of atherosclerotic lesion and subsequent complications are smoking, high Low Density Lipoprotein –Cholesterol (LDL-C), high blood pressure, obesity and alcohol.
 Materials and Methods: This study was carried on 20 healthy individuals as a control group, 15 patients with stable angina, 15 patients with recent myocardial infraction (MI) and 15 patient 24-hours post MI. All subjects were males with age 45±65 years and underwent exclusion/inclusion criteria. COX-2, MMPs levels were quantitatively measured by enzyme-linked immunosorbent assay (ELISA).
 Results: There is insignificant differences in both COX-2 and MMP-2 levels among studied groups (P = 0.450 and 0.246 respectively) .On other hand, MMP-9 demonstrate a significant elevation in its level in studied groups (P = 0.014): its level significantly increase in stable angina (31.474 ± 12.188 ng/ml) compared to both control (9.920 ± 0.075 ng/ml) and Post MI groups (16.012 ± 13.852 ng/ml) (P = 0.001 and 0.004 respectively) and significantly increase in MI group (26.020 ± 14.792 ng/ml) when compared to both control (P = 0.006) and post MI (P = 0.038) groups.
 Conclusion: We can conclude that both COX-2 and MMP-2 cannot be used as markers for diagnosis of stable angina or MI. While MMP-9 as it showed significant elevation in its level in MI and then decrease in post MI, it can be considered as a good marker for confirming the diagnosis of MI and post MI stage.

The Relationship Between Adiponectin Serum Level and Coronary Artery Disease in Type 2 Diabetic Patients

Adiponectin is an adipocytokine that has a higher serum level in healthy people. In type 2 diabetes, insulin resistance, hypertension, MI, and dyslipidemia, the serum level of adiponectin is lower than 4 µg/mL. Adiponectin is proved to have a protective role against atherosclerotic changes where its low serum levels in type 2 diabetes can lead to the progression of atherosclerotic lesions. In this study, we aimed to survey the possible effects of adiponectin in the development of coronary artery disease in type 2 diabetics. Thirty diabetic cases with coronary artery disease, 30 diabetic cases without known coronary artery disease, and a group of 30 healthy volunteers, all of them were between 18-65-year-old, were entered ourstudy. We gathered demographic data by performing a physical examination followed by filling a checklist and a set of laboratory tests. All the groups were sex and age-matched (P=0.284 and P=0.163 respectively). CAD group had the lowest HBA1C (P<0.001). Both LDL and HDL were also lower in the CAD group (P<0.001). Adiponectin was also lower in the CAD group when compared to other groups (P<0.008) or when compared with only normal diabetics (P<0.002). We found a correlation between adiponectin and HDL (r=0.348, P=0.008), suggesting each unit of reduction in serum level of adiponectin could increase the chance of coronary artery disease by 38% in diabetics. In this study, we showed that the lower serum level of adiponectin is correlated with an increased risk of coronary artery disease in type 2 diabetics.

The Role of Matrix Metalloproteinases in the Progression and Vulnerabilization of Coronary Atherosclerotic Plaques

Abstract Extracellular matrix (ECM) plays an important role in the development and progression of atherosclerotic lesions. Changes in the ECM are involved in the pathophysiology of many cardiovascular diseases, including atherosclerosis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases, also known as matrixins, with proteolytic activity in the ECM, being responsible for the process of tissue remodeling in various systemic pathologies, including cardiac and vascular diseases. MMPs play an important role in maintaining normal vascular structure, but also in secondary cardiovascular remodeling, in the formation of atherosclerotic plaques and in their vulnerabilization process. In addition to the assigned effect of MMPs in vulnerable plaques, they have a well-defined role in post-infarction ventricular remodeling and in various types of cardiomyopathies, followed by onset of congestive heart failure, with repeated hospitalizations and death. The aim of this manuscript was to provide a summary on the role of serum matrix metalloproteinases in the process of initiation, progression and complication of atherosclerotic lesions, from a molecular level to clinical applicability and risk prediction in patients with vulnerable coronary plaques.

CC Chemokine Receptor 5 Targeted Nanoparticles Imaging the Progression and Regression of Atherosclerosis Using Positron Emission Tomography/Computed Tomography.

Chemokines and chemokine receptors play an important role in the initiation and progression of atherosclerosis by mediating the trafficking of inflammatory cells. Chemokine receptor 5 (CCR5) has major implications in promoting the development of plaques to advanced stage and related vulnerability. CCR5 antagonist has demonstrated the effective inhibition of atherosclerotic progression in mice, making it a potential biomarker for atherosclerosis management. To accurately determine CCR5 in vivo, we synthesized CCR5 targeted Comb nanoparticles through a modular design and construction strategy with control over the physiochemical properties and functionalization of CCR5 targeting peptide d-Ala-peptide T-amide (DAPTA-Comb). In vivo pharmacokinetic evaluation through 64Cu radiolabeling showed extended blood circulation of 64Cu-DAPTA-Combs conjugated with 10%, 25%, and 40% DAPTA. The different organ distribution profiles of the three nanoparticles demonstrated the effect of DAPTA on not only physicochemical properties but also targeting efficiency. In vivo positron emission tomography/computed tomography (PET/CT) imaging in an apolipoprotein E knockout mouse atherosclerosis model (ApoE-/-) showed that the three 64Cu-DAPTA-Combs could sensitively and specifically detect CCR5 along the progression of atherosclerotic lesions. In an ApoE-encoding adenoviral vector (AAV) induced plaque regression ApoE-/- mouse model, decreased monocyte recruitment, CD68+ macrophages, CCR5 expression, and plaque size were all associated with reduced PET signals, which not only further confirmed the targeting efficiency of 64Cu-DAPTA-Combs but also highlighted the potential of these targeted nanoparticles for atherosclerosis imaging. Moreover, the up-regulation of CCR5 and colocalization with CD68+ macrophages in the necrotic core of ex vivo human plaque specimens warrant further investigation for atherosclerosis prognosis.

Evaluation of Plaque Characteristics and Inflammation Using Magnetic Resonance Imaging.

Atherosclerosis is an inflammatory disease of large and medium-sized arteries, characterized by the growth of atherosclerotic lesions (plaques). These plaques often develop at inner curvatures of arteries, branchpoints, and bifurcations, where the endothelial wall shear stress is low and oscillatory. In conjunction with other processes such as lipid deposition, biomechanical factors lead to local vascular inflammation and plaque growth. There is also evidence that low and oscillatory shear stress contribute to arterial remodeling, entailing a loss in arterial elasticity and, therefore, an increased pulse-wave velocity. Although altered shear stress profiles, elasticity and inflammation are closely intertwined and critical for plaque growth, preclinical and clinical investigations for atherosclerosis mostly focus on the investigation of one of these parameters only due to the experimental limitations. However, cardiovascular magnetic resonance imaging (MRI) has been demonstrated to be a potent tool which can be used to provide insights into a large range of biological parameters in one experimental session. It enables the evaluation of the dynamic process of atherosclerotic lesion formation without the need for harmful radiation. Flow-sensitive MRI provides the assessment of hemodynamic parameters such as wall shear stress and pulse wave velocity which may replace invasive and radiation-based techniques for imaging of the vascular function and the characterization of early plaque development. In combination with inflammation imaging, the analyses and correlations of these parameters could not only significantly advance basic preclinical investigations of atherosclerotic lesion formation and progression, but also the diagnostic clinical evaluation for early identification of high-risk plaques, which are prone to rupture. In this review, we summarize the key applications of magnetic resonance imaging for the evaluation of plaque characteristics through flow sensitive and morphological measurements. The simultaneous measurements of functional and structural parameters will further preclinical research on atherosclerosis and has the potential to fundamentally improve the detection of inflammation and vulnerable plaques in patients.

Multislice computed tomography in the evaluation of coronary atherosclerosis dynamics: data three-year observation in patients with myocardial infarction-segment elevation ST and stenting of coronary arteries

The aim – to use multislice computed tomography (MSCT)-coronary angiography data to determine the presence of atherosclerotic process progression in coronary vessels in the dynamics of the three-year follow-up period in patients after STEMI and coronary artery stenting.Materials and methods. 66 MSCT-coronary angiography studies were performed in 19 men after primary myocardial infarction with ST-segment elevation (STEMI) and coronary artery stenting. All patients were male, ranging in age from 38 to 66 years, with a mean (Me 55.6; (Q1–Q3 (49–64)) years, and 18 of 19 (94.0 %) patients developed Q-MI. 1 patient (6 %) had non-Q-MI. A month after acute MI, patients underwent MSCT of the heart with coronary vascular contrast. Re-examination was performed one, two and three years after the development of STEMI. According to the results of MSCT coronary angiography determined the functional status of stents, as well as the presence or exclusion of signs of restenosis (about 50 % or more) or thrombosis 100 % – occlusion) in the stent coronary artery and in non-infarction-causing arteries. With the progression of atherosclerotic plaque, an increase in atherosclerotic plaque of more than 20 % was taken into account compared to the previous study.Results and discussion. By the end of the first year after MI in 11 of 19 (57.9 %) patients according to MSCT-coronary angiography, no progression of atherosclerotic lesions of the coronary arteries was observed. 1 patient (5.6 %) had stent restenosis, which was confirmed by CAG data. Progression of atherosclerotic lesions was observed in 7 patients (36.8 %), 3 of them (16.6 %) in the stent artery, and in 4 patients in the non-infarction-causing artery. In the second year after myocardial infarction, compared with the annual examination, in 6 of 14 (42.9 %) no progression of atherosclerosis was observed, and in 7 of 14 (50 %) progression of atherosclerotic lesions not in the stent artery, and only in 1 of 14 – progression of atherosclerosis in the stent artery. In the third year after the development of MI, 10 of 14 (71.4 %) had no progression of atherosclerosis, and 4 patients showed progression in both IOA and other arteries.Conclusions. MSCT coronary angiography is an informative method in assessing the functional status of stents and determining the progression of coronary atherosclerosis in the infarct-causing artery and other coronary arteries in patients after MI and coronary artery stenting in the dynamics of three-year follow-up. The lack of progression of atherosclerosis was accompanied by slightly lower levels of low-density lipoprotein cholesterol, compared with patients with progression of atherosclerosis.

Inflammatory Chemokines in Atherosclerosis.

Atherosclerosis is a long-term, chronic inflammatory disease of the vessel wall leading to the formation of occlusive or rupture-prone lesions in large arteries. Complications of atherosclerosis can become severe and lead to cardiovascular diseases (CVD) with lethal consequences. During the last three decades, chemokines and their receptors earned great attention in the research of atherosclerosis as they play a key role in development and progression of atherosclerotic lesions. They orchestrate activation, recruitment, and infiltration of immune cells and subsequent phenotypic changes, e.g., increased uptake of oxidized low-density lipoprotein (oxLDL) by macrophages, promoting the development of foam cells, a key feature developing plaques. In addition, chemokines and their receptors maintain homing of adaptive immune cells but also drive pro-atherosclerotic leukocyte responses. Recently, specific targeting, e.g., by applying cell specific knock out models have shed new light on their functions in chronic vascular inflammation. This article reviews recent findings on the role of immunomodulatory chemokines in the development of atherosclerosis and their potential for targeting.

Description of Visfatin Adipokine and its Roles on Inflammation and Coronary Heart Disease

Coronary heart disease (CHD) is a generic designation for a group of related syndromes resulting from myocardial ischemia – an imbalance between cardiac blood supply (perfusion) and myocardial oxygen demand. Visfatin (VF) is a recently discovered adipokine with different functions, Visfatin is mainly found in visceral adipose tissue and mimics insulin in lowering plasma glucose levels and, Visfatin emerges as a player in the development and progression of atherosclerotic lesions by directly promoting smooth muscle cell proliferation, Aberrant angiogenesis is now considered a feature of the atherogenic process in both coronary and carotid diseases. This adipokine was previously known as a pre-B-cell colony-enhancing factor (PBEF) or Nicotinamide phosphoribosyltransferase (NAmPRTase or Nampt) an enzyme that in humans is encoded by the NAMPT gene and demonstrated to be an intracellular protein with a key enzyme role in nicotinamide adenine dinucleotide (NAD)

MECHANISMS OF ATHEROGENESIS AND ITS INTENSIFICATION IN PATIENTS WITH RHEUMATOID ARTHRITIS

The article describes the role of cholesterol crystals (CS) in the mechanisms of development in the inner lining of arteries of inflammation – granulomatosis, induced by foreign bodies. The smallest CS crystals are found already in early atherosclerotic lesions. They are a factor in the initiation and exacerbation of atherosclerosis (At), cause cell damage and apoptosis. The formation of crystals within the necrotic nuclei of plaques can lead to an increase in their volume and to rupture. It has been shown that damage to the membranes of macrophages phagolysosomes by absorbed CS crystals leads to the inclusion of protein complexes – inflammasomes – in the inflammatory process, which trigger the inflammatory signaling cascade and are responsible for the secretion of pro-inflammatory cytokines. Inflammasomes NLRP3 are necessary for the process of atherogenesis; their activation is a link between the metabolism of cholesterol and inflammation involving macrophages. Unlike At, RA is manifested by autoimmune inflammation and immunocomplex vasculitis. When these diseases are combined, the effects of proinflammatory cytokines add up, an increase in the severity of inflammation, increased tissue damage and progression of atherosclerotic arterial lesions. The accelerated development of At in RA patients is facilitated by a combination of the action of traditional risk factors for atherogenesis and damage to the walls (endothelium) of arteries by immune complexes, complement, neutrophils and lymphocytes with an increase in their permeability to the lipid factor. The deposition of immune complexes in the capillaries of plaques leads to damage to their walls, destabilization of plaques and the development of acute cardiovascular events. The intensification of lipid accumulation and inflammation in the plaques of RA patients is confirmed in the section. Anticytokine drugs, primarily TNF-α and IL-1β antagonists, are pathogenetically substantiated agents for the progression of At in patients with RA. Statins remain a widely used class of drugs. They, in addition to hypolipidemic, immunomodulatory and anti-inflammatory effects, affect the crystallization of cholesterol, dissolve crystals and stabilize plaques.

Скринінг сонних артерій у хворих на цукровий діабет: методологія і клінічна значимість

Цукровий діабет (ЦД) є незалежним фактором ризику розвитку фатальних і нефатальних серцево-судинних захворювань (ССЗ). На сьогодні, за даними Всесвітньої організації охорони здоров’я, у світі на ЦД хворіє близько 422 млн людей, що становить 8,8% усього населення планети. Встановлено, що ССЗ є основною причиною смерті у хворих на ЦД. Також тривожить те, що за ЦД досить часто спостерігається ураження судин. Причиною цьому є патогенетично обгрунтоване швидке прогресування атеросклеротичного ураження судин, яке може безсимптомно прогресувати десятки років до моменту настання несприятливих серцево-судинних подій. Варто враховувати, що на фоні ЦД зміни судинної стінки у вигляді атеросклеротичного ураження мають більш прогресуючий перебіг, ніж у пацієнтів без ЦД. Все це вказує на потребу ранньої діагностики змін судинної стінки у хворих на ЦД. Підтвердженням цьому є результати низки клінічних досліджень, в яких рекомендовано розцінювати ультразвукову діагностику (УЗД) судин, а саме сонних артерій, як скринінговий метод «першої лінії» атеросклеротичного ураження, особливо у хворих на ЦД. Цей метод є не лише неінвазивним, безпечним, безболісним, швидким та не дорогим, але й достовірним. УЗД судин дає можливість на ранніх етапах виявляти початкові і вже наявні атеросклеротичні зміни судинної стінки в безсимптомних хворих, контролювати ефективність лікування та подальше прогресування захворювання. У статті представлено методологію визначення і клінічну значимість ранніх маркерів атеросклерозу — товщина комплексу інтима-медіа та наявність атеросклеротичних бляшок — за допомогою УЗД судин. Використання УЗД сонних артерій, як метода вибору у хворих на ЦД, дозволить своєчасно виявляти ризик розвитку ССЗ та їх ускладнень у пацієнтів на ЦД.

Beneficial Effects of L-carnitine on Cholesterol-Induced Atherosclerosis in Rabbits: An Animal Model Study

Twenty five rabbits were randomized into five groups (n = 5): Normal Control group(NC) were kept on a plain chow diet for 75 days. AT group were kept on a hypercholesterolaemicdiet for 75 days. ATO (atorvastatin) group were fed the same diet and receivedatorvastatin orally (20mg/kg/day) from day 45 for 30 days. L group were fed thesame diet and intraperitoneal L-carnitine (250 mg/kg/day) from day 45 for 30 days (completionof treatment). ATO/L group were fed the same diet and atorvastatin orally(l0 mg/kg/day) and L-carnitine intraperitoneally (125 mg/kg/day) from day 45 for 30 days.Histopathological investigations of aorta and assessment of serum profile were carried out to determine Blood urea nitrogen (BUN), creatinine (Cr), Sodium (Na), potassium (K), Phosphorus (P), triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and Alkaline phosphatase(ALK). The aorta wall of hypercholesterolaemic rabbits showedfoam cells with disrupted endothelial lining and changed muscle fibers. The animals of ATO and ATO/L groups had normal aorta wall. TG significantly increased in hypercholesterolaemic rabbits.L-carnitine treatment significantly reduced TG (P 0.05) except for L group, where BUN level wassignificantly higherthan those in ATO and ATO/L groups (P<0.05). Serum AST, ALT and ALK levels were significantly reduced in L-carnitine treated animals compared to ATO group (P<0.05). L-carnitine prevented progression of atherosclerotic lesions.

Influence of near-wall PIV data on recirculation hemodynamics in a patient-specific moderate stenosis: Experimental-numerical comparison.

Recirculation zones within the blood vessels are known to influence the initiation and progression of atherosclerotic lesions. Quantification of recirculation parameters with accuracy remains subjective due to uncertainties in measurement of velocity and derived wall shear stress (WSS). The primary aim is to determine recirculation height and length from PIV experiments while validating with two different numerical methods: finite-element (FE) and -volume (FV). Secondary aim is to analyze how FE and FV compare within themselves. PIV measurements were performed to obtain velocity profiles at eight cross sections downstream of stenosis at flow rate of 200ml/min. WSS was obtained by linear/quadratic interpolation of experimental velocity measurements close towall. Recirculation length obtained from PIV technique was 1.47cm and was within 2.2% of previously reported in-vitro measurements. Derived recirculation length from PIV agreed within 6.8% and 8.2% of the FE and FV calculations, respectively. For lower shear rate, linear interpolation with five data points results in least error. For higher shear rate either higher order (quadratic) interpolation with five data points or lower order (linear) with lesser (three) data points leads to better results. Accuracy of the recirculation parameters is dependent on number of near wall PIV data points and the type of interpolation algorithm used.

Amorphous silica nanoparticles accelerated atherosclerotic lesion progression in ApoE\u2212/\u2212 mice through endoplasmic reticulum stress-mediated CD36 up-regulation in macrophage

BackgroundThe biosafety concern of silica nanoparticles (SiNPs) is rapidly expanding alongside with its mass production and extensive applications. The cardiovascular effects of SiNPs exposure have been gradually confirmed, however, the interaction between SiNPs exposure and atherosclerosis, and the underlying mechanisms still remain unknown. Thereby, this study aimed to explore the effects of SiNPs on the progression of atherosclerosis, and to investigate related mechanisms.ResultsWe firstly investigated the in vivo effects of SiNPs exposure on atherosclerosis via intratracheal instillation of ApoE−/− mice fed a Western diet. Ultrasound microscopy showed a significant increase of pulse wave velocity (PWV) compared to the control group, and the histopathological investigation reflected a greater plaque burden in the aortic root of SiNPs-exposed ApoE−/− mice. Compared to the control group, the serum levels of total triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were elevated after SiNPs exposure. Moreover, intensified macrophage infiltration and endoplasmic reticulum (ER) stress was occurred in plaques after SiNPs exposure, as evidenced by the upregulated CD68 and CHOP expressions. Further in vitro, SiNPs was confirmed to activate ER stress and induce lipid accumulation in mouse macrophage, RAW264.7. Mechanistic analyses showed that 4-PBA (a classic ER stress inhibitor) pretreatment greatly alleviated SiNPs-induced macrophage lipid accumulation, and reversed the elevated CD36 expression induced by SiNPs.ConclusionsOur results firstly revealed the acceleratory effect of SiNPs on the progression of atherosclerosis in ApoE−/− mice, which was related to lipid accumulation caused by ER stress-mediated upregulation of CD36 expression in macrophage.Graphical abstract

Association between galectin-3 levels and isolated coronary artery ectasia.

Coronary artery ectasia (CAE) is a well-recognised disorder characterised by abnormal dilation of the coronary arteries. Underlying mechanisms associated with abnormal luminal dilation in CAE remain to be elucidated. However, histopathological features resemble those of coronary atherosclerosis. Galectin-3 (Gal-3) is a valuable biomarker for both progression and destabilisation of atherosclerotic lesions. To the best of our knowledge, there is no study in the literature examining serum Gal-3 levels in patients with isolated CAE. In the present study, therefore, we aimed to investigate the possible relationship between serum Gal-3 levels and isolated CAE. Between March 2016 and March 2017 this prospective, case-controlled study included a total of 49 consecutive isolated CAE patients (31 males, 18 females) diagnosed with CAE by coronary angiography at the catheter laboratory of Medeniyet University, Goztepe Training and Research Hospital, and 43 individuals (19 males, 24 females) with normal coronary arteries. Physical examination, medical history, blood biochemistry and transthoracic echocardiography were performed in both groups. Serum concentrations of Gal-3 were measured using blood samples. Median Gal-3 levels were significantly higher in isolated CAE patients than in the controls [23.2 (23.9 ± 7.1) vs 16.8 ng/ml (17.8 ± 7.3); p < 0.001]. According to the Markis classification, the extent of CAE was not correlated with Gal-3 levels (p = 0.41). Multivariate regression analysis revealed that Gal-3 concentration was an independent predictor of isolated CAE. Our study results suggest that Gal-3 serum concentrations significantly increased in patients with isolated CAE, indicating that Gal-3 may be involved in the pathogenesis of isolated CAE.

Selected biomarkers of atherosclerosis - clinical aspects

Atherosclerosis is a inflammatory-immunological-degenerative process. Cardiovascular diseases account for 42% of premature deaths among men and 52% of premature deaths among woman. Identification of classical biomarkers of atherosclerosis, such as LDL, HDL and triglycerides may not be helpful in patients with moderate or unusual cardiovascular risk. Non-classical indicators of atherosclerosis include markers of the inflammatory proces, mar-kers of atherosclerotic plaque injury, acute phase proteins, ischemic markers, markers of tissue necrosis, markers of myocardial dysfunction. The identification of CVD biomarkers enables the classification of patients to appropriate cardiovascular risk groups. Knowledge about the CVD risk group makes it possible to take rapid therapeutic intervention aimed at limiting this risk. Pharmacotherapy for cardiovascular diseases is primarily based on lowering cholesterol’s level in the blood. Additional properties of statins (the most important lipid-lowering drugs) enable their pleiotropic effect by limiting the progression of atherosclerotic lesions by reducing the volume of atherosclerotic plaque. Further research on the pathogenesis of atherosclerosis will allow to learn new risk factors and new biomarkers of this disease.

Subcutaneous administration of casein attenuates atherosclerotic progression in male apoE-/- mice fed with high-fat diet.

The impact of casein on atherosclerotic lesion progression remains controversial. In this study, we tested the effect of casein on atherosclerotic development and its potential mechanisms in male apolipoprotein E knockout (apoE‐/‐) mice fed with high‐fat diet (HFD). Male apoE‐/‐ mice fed with HFD were randomized into HFD group (subcutaneous injection with 0.5 ml of 0.9% sodium chloride daily, n = 6) and HFD + Casein group (subcutaneous injection with 0.5 ml of 10% casein daily, n = 6). Body weight was recorded at baseline and once a week thereafter. After 12 weeks of treatment, plasma lipid and inflammatory markers, and histological characterization of atherosclerotic plaques in the aortic arch and aortic sinus were analyzed. There was no significant difference in weight gain between the two groups after 12 weeks of treatment. Plasma levels of total cholesterol (TC), triglyceride (TG), and low‐density lipoprotein cholesterol (LDL‐C) were significantly lower, while high‐density lipoprotein cholesterol (HDL‐C) level tended to be higher in the HFD + Casein group compared with the HFD group. The positive percentages of atherosclerotic lesions in aortic arch and aortic sinus as well as collagen deposition in aortic sinus plaques were significantly lower in the HFD + Casein group compared with the HFD group. Plasma levels of interleukin (IL)‐1β and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) were also significantly lower in the HFD + Casein group compared with the HFD group. In conclusion, subcutaneous administration of casein attenuates atherosclerotic lesion progression, possibly through decreasing fibrosis and inflammatory responses in male apoE‐/‐ mice fed with HFD.

Sestrin1 inhibits oxidized low-density lipoprotein-induced activation of NLRP3 inflammasome in macrophages in a murine atherosclerosis model.

Macrophages play a crucial role in the progression of atherosclerotic lesions. In the current study, we analyzed the expression and function of sestrin1 (SESN1) in the aorta macrophages in a murine atherosclerosis model. We identified high SESN1 expression in the aorta macrophages in atherosclerotic mice. Using lentivirus-mediated SESN1 overexpression in macrophages, we found that SESN1 inhibited oxidized low-density lipoprotein-induced NLRP3 inflammasome activation in lipopolysaccharide (LPS)-primed macrophages, as evidenced by less ASC-NLRP3 complex formation, lower caspase-1 activation, and lower generation of mature IL-1β. Besides, SESN1 impeded oxidized low-density lipoprotein-induced activation of NK-κB signaling in macrophages. Furthermore, SESN1 suppressed cholesterol crystal-induced NLRP3 inflammasome activation and foam cell formation. Adoptive transfer of SESN1 overexpressing macrophages reduced the expression of pro-inflammatory cytokines in infiltrating macrophages and the whole aorta tissue. Adoptive transfer of SESN1 knockdown macrophages enhanced the expression of pro-inflammatory cytokines in infiltrating macrophages and the whole aorta tissue. Overall, our study sheds light on the significance of SESN1 for macrophage-mediated aorta inflammation.

Macrophage-Enriched lncRNA RAPIA: A Novel Therapeutic Target for Atherosclerosis.

Despite the current antiatherosclerotic and antithrombotic therapies, the incidence of advanced atherosclerosis-associated clinical events remains high. Whether long noncoding RNAs (lncRNAs) affect the progression of atherosclerosis and whether they are potential targets for the treatment of advanced atherosclerosis are poorly understood. Approach and Results: The progression of atherosclerotic lesions was accompanied by dynamic alterations in lncRNA expression, as revealed by RNA sequencing and quantitative polymerase chain reaction. Among the dynamically changing lncRNAs, we identified a novel lncRNA, lncRNA Associated with the Progression and Intervention of Atherosclerosis (RAPIA), that was highly expressed in advanced atherosclerotic lesions and in macrophages. Inhibition of RAPIA in vivo not only repressed the progression of atherosclerosis but also exerted atheroprotective effects similar to those of atorvastatin on advanced atherosclerotic plaques that had already formed. In vitro assays demonstrated that RAPIA promoted proliferation and reduced apoptosis of macrophages. A molecular sponge interaction between RAPIA and microRNA-183-5p was demonstrated by dual-luciferase reporter and RNA immunoprecipitation assays. Rescue assays indicated that RAPIA functioned at least in part by targeting the microRNA-183-5p/ITGB1 (integrin β1) pathway in macrophages. In addition, the transcription factor FoxO1 (forkhead box O1) could bind to the RAPIA promoter region and facilitate the expression of RAPIA. The progression of atherosclerotic lesions was accompanied by dynamic changes in the expression of lncRNAs. Inhibition of the pivotal lncRNA RAPIA may be a novel preventive and therapeutic strategy for advanced atherosclerosis, especially in patients resistant or intolerant to statins.

Low shear stress induces endothelial cell apoptosis and monocyte adhesion by upregulating PECAM‑1 expression.

Low shear stress serves an important role in the initiation and progression of atherosclerotic lesions, with an impact on progression, but its detailed mechanisms are .not yet fully known. The present study aimed to investigate endothelial cell (EC) apoptosis, as well as monocyte adhesion induced by low shear stress and the potential underlying mechanisms. The expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) was demonstrated to be enhanced in human umbilical vascular ECs with a trend that was associated with time when stimulated by low shear stress compared with unstimulated cells. EC apoptosis was increased under low shear stress compared with unstimulated cells, and knockdown of PECAM-1 inhibited this process. Furthermore, downregulation of PECAM-1 reduced monocyte adhesion induced by low shear stress compared with that in the negative control cells. Mechanistically, PECAM-1 small interfering RNA transfection increased Akt and forkhead box O1 phosphorylation under low shear stress conditions compared with that in the negative control cells. Collectively, the findings of the present study revealed that low shear stress induced EC apoptosis and monocyte adhesion by upregulating PECAM-1 expression, which suggested that PECAM-1 may be a potential therapeutic target for atherosclerosis.