Process Of Atherosclerosis Research Articles

Correlation of Hba1c, Triglyceride, HDL with the Degree of Stenosis in Coronary Heart Patients with Type 2 Diabetes Mellitus

Background: Coronary Heart Disease (CHD) is a disease caused by the narrowing of the coronary artery wall as a result of the atherosclerosis process. Atherosclerosis plays an important role from the beginning of plaque formation until plaque rupture which causes blood clots. Diabetes mellitus and dyslipidemia are one of the major risk factors for CHD. In patients with type 2 Diabetes Mellitus, there was an altered lipid profile which led to endothelial damage that caused the formation of atherosclerosis. HDL cholesterol labeled as good cholesterol was decreased due to uncontrolled LDL cholesterol labeled as bad cholesterol. LDL cholesterol synthesis process was disrupted then causing plaque formation in the arteries which causes CHD. Aim: The aim of this study was to analysis correlation between HbA1c levels, triglyceride levels, HDL levels and the degree of stenosis in coronary heart disease sufferers with type 2 diabetes mellitus. Method: This study was an observational cross-sectional analytical study with total of 51 patients with CHD who underwent cardiac catheterization at Telogorejo Hospital. Semarang. The correlation test in this study using the Spearman test with p 0.05 is considered significant. Results: Results of this study show that there is no significant correlation between HbA1C levels and triglyceride levels (p= 0.793), and Hba1C with the degree of stenosis was (p= 0.685) but, there was significant correlation between HDL cholesterol level with the degree of stenosis (p=0.015). Conclusion: It was concluded that there was no significant correlation between the correlation of HbA1c levels and triglyceride levels with the degree of stenosis and there was a moderately negative significant correlation between HDL levels and the degree of stenosis.

A multi-target and responsive nanoplatform (MM/ZnS/ATV) combining H2S and atorvastatin for enhanced atherosclerosis therapy

Atherosclerosis, a chronic inflammatory disease characterized by the formation of atherosclerotic plaques in the arterial walls. The pathological process of atherosclerosis mainly contains lipid metabolism disorder, endothelial dysfunction, and progressive inflammation. Given the complexity of pathological process, treatments based on a single target might have very limited therapeutic efficacy. Thus, developing a nanoplatform to obtain an enhanced multi-target therapy is promising. Hydrogen sulfide (H2S) has various functions including anti-inflammation, anti-oxidation and endothelial protection. In this study, a responsive multi-target nanoplatform (MM/ZnS/ATV) combining the functions of H2S and atorvastatin was developed. The acidic microenvironment of the plaque can accelerate ZnS hydrolysis to trigger H2S and atorvastatin release. The responsive H2S release from ZnS can overcome the shortcomings of rapid H2S release from H2S donors in vivo. Furthermore, the ZnS hydrolysis-mediated H+ consumption in the microenvironment can reduce acidity to some extent. Results showed macrophage membranes (MM) coating reduced the phagocytosis of nanoparticles and increased the bioavailability. In vitro studies demonstrated that H2S release from MM/ZnS/ATV inhibited ROS-induced endothelial cell apoptosis and repaired the damaged endothelium. Moreover, atorvastatin released from MM/ZnS/ATV regulated lipid metabolism and reduced the blood lipid content. Both in vitro and in vivo studies confirmed MM/ZnS/ATV exhibited excellent therapeutic efficacy. Specifically, in vivo results showed that H2S combined with atorvastatin effectively reduced inflammatory infiltration, and promoted plaque regression and stabilization. Our study provides a promising strategy for atherosclerosis therapy.

Familial hypercholesterolemia care by Dutch pediatricians—mind the gaps

PurposeFamilial hypercholesterolemia (FH) leads to elevated low-density lipoprotein cholesterol levels, which increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). Since the first functional and morphologic changes of the arterial wall occur in childhood, treatment should start early in childhood to mitigate the elevated risk of ASCVD. Pediatricians play an important role in the detection and care of children with FH. In this study, we aim to explore potential gaps in FH care amongst Dutch pediatricians, in order to enhance their knowledge and awareness of detecting and treating children with FH.MethodsAn anonymous online survey, deployed using Google Forms, including 26 closed and semi-closed questions on FH care in children was distributed by the Dutch Association of Pediatrics via a newsletter to which the majority of the practicing Dutch pediatricians subscribe. In addition, we requested that the pediatric departments of all Dutch hospitals in the Netherlands distribute this survey personally among their employed pediatricians. Respondents were instructed to answer the questions without any help or use of online resources.ResultsBetween September 1st, 2023 and November 1st, 2023, 158 (an estimated 11% response rate) Dutch pediatricians completed the survey. They reported a median (IQR) of 15.0 (6.0–22.0) years of experience as a pediatrician, and 34 (21.5%) were working in academic hospitals. The majority (76.6%) of pediatricians correctly identified a typical FH lipid profile but 68 (43.0%) underestimated the true prevalence of FH (1:300). Underestimation and unawareness of the increased risk of FH patients for ASCVD were reported by 37.3% and 25.9% of pediatricians, respectively. Although 70.9% of the pediatricians correctly defined FH, only 67 (42.4%) selected statins and ezetimibe to treat severe hypercholesterolemia.Conclusions:The results of this study suggest significant gaps in knowledge and awareness of FH in children among Dutch pediatricians. FH care in children needs improvement through educational and training initiatives to mitigate the life-long risk of ASCVD from early life.What is Known:• Familial hypercholesterolemia (FH) leads to elevated LDL-cholesterol levels, which increases the risk of premature atherosclerotic cardiovascular disease (ASCVD).• The process of atherosclerosis starts in childhood• Pediatricians play an important role in the detection and treatment of children with FH.What is New:• Our results highlight significant gaps in care for children with FH amongst pediatricians and this may lead to suboptimal detection and treatment.• FH care in children needs improvement by educational initiatives to ultimately prevent ASCVD in adulthood.

Unraveling the mechanism of malancao in treating ulcerative colitis: A multi-omics approach

BACKGROUND Malancao (MLC) is a traditional Chinese medicine with a long history of utilization in treating ulcerative colitis (UC). Nevertheless, the precise molecular mechanisms underlying its efficacy remain elusive. This study leveraged ultra-high-performance liquid chromatography coupled with exactive mass spectrometry (UHPLC-QE-MS), network pharmacology, molecular docking (MD), and gene microarray analysis to discern the bioactive constituents and the potential mechanism of action of MLC in UC management. AIM To determine the ingredients related to MLC for treatment of UC using multiple databases to obtain potential targets for fishing. METHODS This research employs UHPLC-QE-MS for the identification of bioactive compounds present in MLC plant samples. Furthermore, the study integrates the identified MLC compound-related targets with publicly available databases to elucidate common drug disease targets. Additionally, the R programming language is utilized to predict the central targets and molecular pathways that MLC may impact in the treatment of UC. Finally, MD are conducted using AutoDock Vina software to assess the affinity of bioactive components to the main targets and confirm their therapeutic potential. RESULTS Firstly, through a comprehensive analysis of UHPLC-QE-MS data and public database resources, we identified 146 drug-disease cross targets related to 11 bioactive components. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted that common disease drug targets are primarily involved in oxidative stress management, lipid metabolism, atherosclerosis, and other processes. They also affect AGE-RAGE and apoptosis signaling pathways. Secondly, by analyzing the differences in diseases, we identified key research targets. These core targets are related to 11 active substances, including active ingredients such as quercetin and luteolin. Finally, MD analysis revealed the stability of compound-protein binding, particularly between JUN-Luteolin, JUN-Quercetin, HSP90AA1-Wogonin, and HSP90AA1-Rhein. Therefore, this suggests that MLC may help alleviate intestinal inflammation in UC, restore abnormal lipid accumulation, and regulate the expression levels of core proteins in the intestine. CONCLUSION The utilization of MLC has demonstrated notable therapeutic efficacy in the management of UC by means of the compound target interaction pathway. The amalgamation of botanical resources, metabolomics, natural products, MD, and gene chip technology presents a propitious methodology for investigating therapeutic targets of herbal medicines and discerning novel bioactive constituents.

Abdominal aortic calcification among gastroenterological and transplant surgery.

This review discusses the increasing global trend towards an aging population, which has resulted in a growing number of surgeries being performed on elderly patients, particularly those living with cancer. The focus was on the implications of abdominal aortic calcification (AAC), an indicator of systemic atherosclerosis, in these patients. This comprehensive review provided evidence detailing the complex processes of atherosclerosis and vascular calcification and various approaches to assess this condition. The prevalence of AAC is related to multiple factors, including cardiovascular disease, inflammation, frailty in various types of gastroenterological surgery. Additionally, notable links were found between AAC, postoperative complications, and patient survival following gastroenterological surgery. This study highlights how AAC could negatively impact the health status of elderly patients and undermine treatment efficacy, stressing the need for more research in this domain to improve patient outcomes.

Arterial structure and function in children with inflammatory bowel disease.

People with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease, including in younger adulthood. This may arise in part from chronic, systemic low-grade inflammation. The process of atherosclerosis may begin in childhood. We sought to determine whether pediatric IBD is associated with adverse changes in arterial structure and function as a marker of early increased cardiovascular risk. We performed a case-control study comparing children with IBD for a median disease duration of 2.49 (interquartile range 1.23, 4.38) years with healthy children. In a single visit, we collected baseline clinical and anthropometric data, and measured blood pressure, pulse wave velocity, carotid artery distensibility, and aortic and carotid intima-media thickness. High-sensitivity C-reactive protein and fasting lipids were measured. We enrolled 81 children with IBD (40 with Crohn's disease, 40 with ulcerative colitis, and 1 with unspecified IBD) and 82 control participants. After adjusting for age, sex, body mass index z-score, blood pressure, and low-density lipoprotein cholesterol, there was no difference in measures of arterial structure and function in children with IBD compared with controls, nor between those with Crohn's disease or ulcerative colitis. We did not show any differences in arterial structure and function in children with a history of IBD for less than 5 years compared with healthy controls. IBD diagnosed in childhood may provide a window of opportunity to actively reduce standard cardiovascular risk factors and improve future cardiovascular outcomes.

Enhancing Cardiovascular Disease Detection through Deep Multimodal Fusion: Integrating Radiology and Electrocardiogram via Convolutional Neural Network

Cardiovascular Diseases (CVDs), also known as heart diseases are related to a process of atherosclerosis, which is when a plaque builds up in the arteries and blocks blood flow. CVDs are an ever-increasing health risk for the general population, and according to the American Heart Association, the number of deaths related to CVDs has surpassed the previous 910,000 all-time record from 2003. To solve this problem, numerous novel approaches have been presented for a solution to decrease such anomalies with traditional methods utilizing computed tomography scans (CT scans) to calculate coronary artery calcium. However, countless problems arise from using CT scans as CT scans are not accessible to the general public, and early diagnosis is especially difficult. So, this research paper aims to explore the potential of AI-driven biomarkers in enhancing the efficiency of CVD diagnosis. Moreover, this study presents a novel approach that uses artificial intelligence to enhance the accuracy of CVD diagnosis. Specifically, this paper suggests an innovative methodology that utilizes the classification of x-ray images that is additionally supplemented by classifying electrocardiograms. These techniques allow for analysis of multi-modal data sources allowing latent information on CVDs to be extracted. Throughout the experiments, the proposed method has proven that it is superior compared to other state-of-the-art methods, as it has achieved an accuracy of 90.49%.

Melatonin suppresses atherosclerosis by ferroptosis inhibition via activating NRF2 pathway.

Melatonin (MLT), a conserved small indole compound, exhibits anti-inflammatory and antioxidant properties, contributing to its cardioprotective effects. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with atherosclerosis disease risk, and is known as an atherosclerosis risk biomarker. This study aimed to investigate the impact of MLT on Lp-PLA2 expression in the atherosclerotic process and explore the underlying mechanisms involved. Invivo, ApoE-/- mice were fed a high-fat diet, with or without MLT administration, after which the plaque area and collagen content were assessed. Macrophages were pretreated with MLT combined with ox-LDL, and the levels of ferroptosis-related proteins, NRF2 activation, mitochondrial function, and oxidative stress were measured. MLT administration significantly attenuated atherosclerotic plaque progression, as evidenced by decreased plaque area and increased collagen. Compared with those in the high-fat diet (HD) group, the levels of glutathione peroxidase 4 (GPX4) and SLC7A11 (xCT, a cystine/glutamate transporter) in atherosclerotic root macrophages were significantly increased in the MLT group. Invitro, MLT activated the nuclear factor-E2-related Factor 2 (NRF2)/SLC7A11/GPX4 signaling pathway, enhancing antioxidant capacity while reducing lipid peroxidation and suppressing Lp-PLA2 expression in macrophages. Moreover, MLT reversed ox-LDL-induced ferroptosis, through the use of ferrostatin-1 (a ferroptosis inhibitor) and/or erastin (a ferroptosis activator). Furthermore, the protective effects of MLT on Lp-PLA2 expression, antioxidant capacity, lipid peroxidation, and ferroptosis were decreased in ML385 (a specific NRF2 inhibitor)-treated macrophages and in AAV-sh-NRF2 treated ApoE-/- mice. MLT suppresses Lp-PLA2 expression and atherosclerosis processes by inhibiting macrophage ferroptosis and partially activating the NRF2 pathway.

Radiation-induced Renal Artery Stenosis

We present a case of a 33 year old male presenting with uncontrolled hypertension, requiring four drugs and renal dysfunction. Investigations revealed calcific atherosclerosis of abdominal aorta and bilateral renal artery stenosis. He had received radiotherapy for abdominal Non-Hodgkin’s lymphoma 14 years ago. Transluminal angioplasty was done on the right side resulting in improved renal function and normalization of blood pressure. Radiotherapy for intra-abdominal malignancy induces atherosclerosis process in arteries within field of irradiation and they manifest after many years of the initial insult.

Broader Perspective on Atherosclerosis-Selected Risk Factors, Biomarkers, and Therapeutic Approach.

Atherosclerotic cardiovascular disease (ASCVD) stands as the leading cause of mortality worldwide. At its core lies a progressive process of atherosclerosis, influenced by multiple factors. Among them, lifestyle-related factors are highlighted, with inadequate diet being one of the foremost, alongside factors such as cigarette smoking, low physical activity, and sleep deprivation. Another substantial group of risk factors comprises comorbidities. Amongst others, conditions such as hypertension, diabetes mellitus (DM), chronic kidney disease (CKD), or familial hypercholesterolemia (FH) are included here. Extremely significant in the context of halting progression is counteracting the mentioned risk factors, including through treatment of the underlying disease. What is more, in recent years, there has been increasing attention paid to perceiving atherosclerosis as an inflammation-related disease. Consequently, efforts are directed towards exploring new anti-inflammatory medications to limit ASCVD progression. Simultaneously, research is underway to identify biomarkers capable of providing insights into the ongoing process of atherosclerotic plaque formation. The aim of this study is to provide a broader perspective on ASCVD, particularly focusing on its characteristics, traditional and novel treatment methods, and biomarkers that can facilitate its early detection.

Exploring Atherosclerosis, Oxidized LDL, Insulin, and Tailored Diet Strategies in Cardiac Patient Assessment

Background Plaque development in vessels which supply blood to heart muscles is caused by atherosclerosis, a slow but progressive process that leads to coronary artery disease (CAD). Arteries become gradually blocked by oxidized fatty acids, with excess fat intake or abnormalities in fat metabolism causing body changes. These changes may lead to an increase in LDL cholesterol, triglycerides, as well as a reduction in HDL cholesterol. The oxidation of excess low density protein (LDL) is a complex process involving many factors, with insulin and obesity playing a significant role and associated with many metabolic syndromes. The current study aims to determine the concentration of oxidized LDL in patients who suffer with cardio vascular diseases (CVDs) and to understand the correlation between oxidation and insulin resistance in cardiac forbearing. Method The method used was to collect data from 30 patients admitted in the cardiology ward. For this purpose, an assessment proforma was built, which included anthropometric measurements, physical activity level, dietary history, and blood tests for lab findings such as lipid profiles. Results The key findings determined that the anomalous function of AKT protein, which is present in pancreatic β cells, as well as disruption in PKC pathway cause phosphorylation in alpha and beta cells of pancreas, which causes diabetes and leads to heart attack. Conclusion The aberrant changes in sugar test and lipid profile including Hb1Ac (9%), fasting blood glucose (250mg/dl), total cholesterol (342mg/dl), LDL (less than 250mg/dl), HDL (49 F mg/dl), and total triglycerides (215mg/dl) causes serious discomfort for patients.

Abstract 1026: Apolipoprotein A1 On High-density Lipoprotein Interferes With Low-density Lipoprotein Binding To Proteoglycans

Background: The entrapment of apolipoprotein (APO) B-100 containing low density lipoproteins (LDL) by proteoglycans (PGs) in the extracellular matrix (ECM) of the arterial intima is a key initial step in the development of atherosclerotic vascular lesions. High density lipoproteins (HDL) can interfere with this process, but the underlying mechanism is not fully understood and is thought to be due to APOE. The aim of this study was to utilize our recently developed quantitative assay that measures the binding of LDL to PGs in the ECM and to investigate how HDL and other apolipoproteins may influence this process. Methods: An in-cell ELISA was used to measure the binding of LDL to PGs in the ECM synthesized by mouse vascular smooth muscle cells. Fast Protein Liquid Chromatography, immunoprecipitation, and immunoblotting analysis were performed to identify how HDL interacts with LDL to prevent binding to ECM-PGs. Results: LDL binding to PGs was inhibited by HDL and APOA1 in a dose dependent manner. Competition experiments showed that HDL does not compete directly with LDL for ECM-PG binding. Instead, our data revealed an association between LDL with APOA1 that diminishes LDL ability to bind ECM-PGs. Conclusion: HDL inhibits LDL binding to ECM-PG through an interaction with its main apolipoprotein, APOA1 that is different from APOE. Further investigation is warranted to understand the role of this interaction in the atherosclerosis process.

Computational simulation of the effects of blood flow velocity on atherosclerosis progression in a human carotid artery

Background Atherosclerosis is a build-up of low-density lipoproteins (LDL) in the channels of blood vessels. This occludes the vessels and, occurring in the carotid arteries, portends conditions that favour stroke. This work is an attempt to mathematically represent the physiological process of atherosclerosis caused by plaques on the walls of the human arteries. Aim Provide insight into the effect of blood flow velocity on wall shear stress and its implications on atherosclerosis progression in a human carotid artery via computational simulation. Methods The effect of blood velocity on plaque growth and progression is simulated using COMSOL multi-physics. The human carotid was modeled in 2-D with Stokes law for model flow. The simulation began with a plaque-free vessel with velocities of 30 m/s – 125 m/s. Results Results showed that the rate of plaque initiation dropped as the blood velocity increased from 30 m/s to 125 m/s; higher inlet velocities gave lower plaque growth; the highest degree of 30% stenosis was recorded at a blood velocity of 30 m/s. Plaque height significantly affects the Plaque wall Stress, PWS, and its distribution around the plaque and arterial wall; higher plaque heights experience higher velocity distribution around the plaque, causing a higher force associated with blood flow around the plaque, resulting in higher compression stress. More compressional stresses are localized around the root, which would encourage growth as well as possible rupture at higher velocities. These ruptured plaques potentially narrow or block the arteries and prevent blood flow. This is atherosclerosis and can lead to a heart attack. Conclusion Results from this study can find significant use in the understanding, management, and treatment of atherosclerosis since the regulation of blood velocity and pressure plays a major role in the progress of atherosclerosis in the carotid artery which raises the risk of stroke.

Transcriptomic analysis reveals the critical role of chemokine signaling in the anti-atherosclerosis effect of Xuefu Zhuyu decoction

Ethnopharmacological relevanceThe process of atherosclerosis (AS) is complicated. Transcriptomics technology can assist in discovering the underlying mechanisms and exploring the key targets of Traditional Chinese Medicine (TCM) against atherosclerosis. AimThis study aimed to investigate targets and signaling pathways significantly related to AS and the potential intervention targets of Xuefu Zhuyu decoction by transcriptomics. Materials and methodsAS models were established by subjecting ApoE-/-mice to an 8-week high-fat diet. Structural changes and plaque formation in the aortic root were observed using hematoxylin-eosin staining (HE staining), while Oil Red O staining was employed to visualize lipid deposition within the aortic root plaque. Movat staining and immunohistochemical staining were conducted to examine the components present in the aortic root plaque. Macrophage content within the plaque was observed through immunofluorescence. Additionally, mRNA sequencing was performed on aortic tissues to identify differentially expressed genes. Enrichment analysis was performed using GO and KEGG analysis. Visualization of the protein-protein interaction (PPI) network was achieved using Cytoscape 3.7.1 and STRING. Western blotting (WB) was employed to assess the protein expression of major differentially expressed genes in the aortic tissue. The drug freeze-dried powder of Xuefu Zhuyu decoction was prepared and the RAW264.7 cells were induced by lipopolysaccharide (LPS) to build an in vitro model. Real-time quantitative PCR was employed to measure the mRNA expression of major differential genes. ResultsAfter ApoE-/- mice were fed with an 8-week high-fat diet, observable changes included the thinning of the aortic root wall, the accumulation of foam cells within the plaque, and the formation of cholesterol crystals in the model group. Treatment with Xuefu Zhuyu (XFZY) decoction for 12 weeks significantly reduced the lipid deposition and the number of macrophages (P < 0.05) and significantly increased the collagen content within the plaque (P < 0.01). Enrichment analysis revealed a high enrichment of the Cytokine-cytokine receptor interaction pathway and Chemokine signaling pathway. Noteworthy genes involved in this response included Ccl12, Ccl22, Cx3cr1, Ccr7, Ccr2, Tnfrsf25, and Gdf5. Xuefu Zhuyu decoction significantly downregulated the expression of CX3CL1 and CX3CR1 (P < 0.05) and upregulated the expression of GDF5 (P < 0.01). Compared with control group, in cell models, the mRNA expressions of Ccl12, Ccl22, and Ccr2 were significantly upregulated (P < 0.05 or P < 0.01). Xuefu Zhuyu decoction significantly downregulated the expression of Ccl12, Ccl22, Cx3cr1, Ccr7 and Ccr2 (P < 0.05 or P < 0.01). ConclusionXuefu Zhuyu decoction demonstrates effective regulation of plaque components, retarding plaque progression and preserving plaque stability by modulating lipid metabolism and inflammatory responses. Subsequent transcriptome analysis identified the Cytokine-cytokine receptor interaction and Chemokine signaling pathway as potential key pathways for the therapeutic effects of Xuefu Zhuyu decoction. This insight not only provides crucial avenues for further exploration into the mechanisms underlying Xuefu Zhuyu decoction but also offers valuable perspectives and hypotheses for enhancing disease prevention and treatment strategies.

Actinidia arguta Extract Containing Myo-Inositol Suppresses TNF-α-Induced VCAM-1 Expression and Monocyte Adhesion to Endothelial Cells via Inhibition of the PTEN/Akt/GSK-3β and NF-κB Signaling Pathways.

The primary inflammatory process in atherosclerosis, a major contributor to cardiovascular disease, begins with monocyte adhering to vascular endothelial cells. Actinidia arguta (kiwiberry) is an edible fruit that contains various bioactive components. While A. arguta extract (AAE) has been recognized for its anti-inflammatory characteristics, its specific inhibitory effect on early atherogenic events has not been clarified. We used tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs) for an in vitro model. AAE effectively hindered the attachment of THP-1 monocytes and reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs. Transcriptome analysis revealed that AAE treatment upregulated phosphatase and tensin homolog (PTEN), subsequently inhibiting phosphorylation of AKT and glycogen synthase kinase 3β (GSK3β) in HUVECs. AAE further hindered phosphorylation of AKT downstream of the nuclear factor kappa B (NF-κB) signaling pathway, leading to suppression of target gene expression. Oral administration of AAE suppressed TNF-α-stimulated VCAM-1 expression, monocyte-derived macrophage infiltration, and proinflammatory cytokine expression in C57BL/6 mouse aortas. Myo-inositol, identified as the major compound in AAE, played a key role in suppressing THP-1 monocyte adhesion in HUVECs. These findings suggest that AAE could serve as a nutraceutical for preventing atherosclerosis by inhibiting its initial pathogenesis.

Incidence and Outcomes of Posterior Circulation Involvement in Moyamoya Disease.

Moyamoya disease (MMD) is a progressive, occlusive disease of the internal carotid arteries and their proximal branches, with the subsequent development of an abnormal vascular network that is rupture-prone. Steno-occlusive changes in the posterior cerebral arteries (PCAs) may contribute to worsened outcomes in patients with MMD; however, there is little information on the incidence and natural history of posterior circulation MMD (PCMMD). We describe clinical PCMMD characteristics in a large cohort of patients with MMD. We retrospectively reviewed patients with MMD treated between 1991 and 2019 at a large academic medical center. Demographics, perioperative outcomes, and radiological phenotypes were recorded for 770 patients. PCA disease was graded as either 0 (no disease), 1 (mild), 2 (moderate), or 3 (severe or occluded) based on cerebral angiography. Patients with angiographically confirmed MMD diagnosis with at least 6 months follow-up and completion of revascularization surgery were included; patients with intracranial atherosclerosis, intracranial dissection, vasculitis, and undefined inflammatory processes were excluded. The presence of stenosis/occlusion was graded radiographically to assess for disease progression and the prevalence of risk factors related to reduced progression-free survival. In all, 686 patients met the inclusion criteria, with PCA disease identified in 282 (41.1%) patients. Of those 282 patients with PCMMD, disease severity ranged from 99 (35.1%) with mild, 72 (25.5%) with moderate, and 111 (39.4%) with severe. The total number of postoperative complications was significantly associated with PCMMD severity (P=0.0067). Additionally, PCMMD severity correlated with worse postoperative modified Rankin Scale scores (P<0.0001). At a mean follow-up of 6.0±3.9 (range, 0.1-25.0) years, a total of 60 (12.6%) patients showed new/worsening PCMMD. The overall postoperative, progression-free survival in patients with PCMMD was 95.4% at 1 year, 82.4% at 3 years, 68.8% at 5 years, and 28.3% at 10 years, with prognostic factors for progression including preoperative PCMMD status, history of tobacco use, and hypertension (P<0.0001, P<0.001, and P<0.0001, respectively). PCA disease involvement in MMD is associated with higher rates of ischemic perioperative complications and worsened functional outcomes, likely due to reduced collateral flow. Ten-year progression of PCA disease is highly likely and should be monitored throughout follow-up; future studies will assess the impact of PCA disease progression on long-term outcomes.

Atherosclerosis and Vine

In light of today's scientific knowledge about the causes and process of atherosclerosis, how to explain and interpret the fact, seemingly very illogical, that the French do not have a high mortality from coronary diseases caused by atherosclerosis, despite the high fat content of everyday nutrition? Such epidemiological ilogenicity, called the French Paradox, has been attributed to daily, moderate consumption of red wines, which proved correct [2]. It has been proven that the beneficial effects of red wine in the process of preventing atherosclerosis can be attributed to the effects of the polyphenols present, likewise, these effects do not only apply to red wine, but also to other drinks, alcoholic and non-alcoholic, containing polyphenols [3]. Studies conducted on beer consumption have produced similar results. [18] It should be noted that the effect of alcohol is described by the J curve, suggesting that moderate alcohol consumption reduces the risk of atherosclerosis, unlike abstinence and excessive alcohol lovers, where this risk is noticeably higher. This effect of red wine is attributed, among other agents, to a significantly increased concentration of high density lipoprotein (HDL) [4]. The paper discusses the effect of HDL particles on nascent chylomicrons in the lymphoma system, which, by entering the circulatory system, affects possible association with atherosclerosis. After such knowledge of the effects of red wine (polyphenols) on the organism, can it be considered that non-consumption of the same and other polyphenols-containing drinks is a certain risk factor? ( In vino veritas).

EFFECTS OF GARCINIA MANGOSTANA LINN PERICARP EXTRACT AND PHYSICAL EXERCISE ON ATHEROEMBOLIC HISTOPATHOLOGIC FEATURES KIDNEY IN WISTAR RATS WITH METABOLIC SYNDROME

Background: Renal atheroembolism is an under-recognized cause of renal failure . Atheroembolism is caused by cholesterol crystals from ulcerated atherosclerotic plaques and is influenced by inflammation and endothelial dysfunction. The formation of complicated atherosclerotic lesions is a prerequisite for the development of cholesterol crystal emboli. Non-pharmacological therapeutic management (such as diet and physical exercise) is an important factor in preventing and reducing the risk of atherogenesis. Garcinia Mangostana Linn pericarp can inhibit the process of atherosclerosis through the reduction of free radicals and improvement of endothelial function Objective: To investigate the effect of Garcinia Mangostana Linn Pericarp administration along with Physical Exercise on the histopathologic features of renal atheroembolism in Wistar rats with metabolic syndrome. Methods: This study is a true experimental study with research subjects in the form of male Rattus norvegicus Wistar rats which were randomly divided into 3 groups. K (not given therapy), P1 (garcinia pericarp extract 800 mg / kg / day with physical exercise), and P2 (nanoemulsion 50 mg / kg / time of administration with physical exercise). Results: In the group treated with garcinia pericarp extract 800 mg/kg bw/day with physical exercise and the group with nanoemulsion 50 mg/kg bw/day with physical exercise, there were no fatty streaks, inflammation, and impaired myocyte coherence. There was 0-5% fibrous connective tissue, one layer of foam cell layer and myocyte-lipid, no cholesterol crystal embolism was found. Conclusion: The administration of Garcinia Mangostana Linn pericarp extract and/or nanoemulsion with physical exercise can have an effect on the histopathological picture of the kidneys of Wistar rats with metabolic syndrome. There was no difference in effect between the two treatments. However, it could not be compared with the group that was not given any treatment because it had died completely before the end of the study period.

PCSK9 plasma concentration is associated with epicardial adipose tissue volume and metabolic control in patients with type 1 diabetes

Patients with type 1 diabetes (T1D) have a greater risk of cardiovascular disease. Proconvertase subtilisin-kexin 9 (PCSK9) is involved in the atherosclerosis process. This study aimed to determine the relationship between PCSK9 levels and epicardial adipose tissue (EAT) volume and cardiometabolic variables in patients with T1D. This was an observational cross-sectional study including 73 patients with T1D. Clinical, biochemical and imaging data were collected. We divided the patients into two groups according to their glycemic control and the EAT index (iEAT) percentile. We performed a correlation analysis between the collected variables and PCSK9 levels; subsequently, we performed a multiple regression analysis with the significant parameters. The mean age was 47.6 ± 8.5 years, 58.9% were men, and the BMI was 26.9 ± 4.6 kg/m2. A total of 31.5%, 49.3% and 34.2% of patients had hypertension, dyslipidemia and smoking habit, respectively. The PCSK9 concentration was 0.37 ± 0.12 mg/L, which was greater in patients with worse glycemic control (HbA1c > 7.5%), dyslipidemia and high EAT volume (iEAT > 75th percentile). The PCSK9 concentration was positively correlated with age (r = 0.259; p = 0.027), HbA1c (r = 0.300; p = 0.011), insulin dose (r = 0.275; p = 0.020), VLDL-C level (r = 0.331; p = 0.004), TG level (r = 0.328; p = 0.005), and iEAT (r = 0.438; p < 0.001). Multiple regression analysis revealed that 25% of the PCSK9 variability was explained by iEAT and HbA1c (p < 0.05). The PCSK9 concentration is associated with metabolic syndrome parameters, poor glycemic control and increased EAT volume in patients with T1D.

CircTLK1: A novel regulator involved in VSMC phenotypic switching and the developmental process of atherosclerosis.

Phenotypic switching of vascular smooth muscle cells (VSMCs) is essential for atherosclerosis development. Circular RNA (circRNA) is a specific non-coding RNA that is produced as a closed-loop structure in mammals, and its specific expression pattern is closely related to its cell type and tissue. To clarify the roles of circTLK1 in VSMC phenotypic switching, we performed qRT-PCR, immunoblotting, and immunostaining. qRT-PCR revealed that circTLK1 was upregulated in both mouse models of atherosclerosis invivo and PDGF (platelet-derived growth factor)-BB-induced VSMCs invitro. Furthermore, the overexpression of circTLK1 promoted PDGF-BB-induced VSMC phenotypic switching. Conversely, experiments performed invivo demonstrate that the knockdown of SMC-specific circTLK1 led to a reduction in the development of atherosclerosis. The relationship between circTLK1 and miR-513a-3p and Krüppel-like factor 4 (KLF4) was detected by RNA immunoprecipitation (RIP), luciferase reporter assay, RNA pull-down, and RNA fluorescence insitu hybridization (RNA FISH). Mechanistically, circTLK1 acted as a sponge for miR-513a-3p, leading to the upregulation of KLF4, a key transcription factor for phenotypic switching. Targeting the circTLK1/miR-513a-3p/KLF4 axis may provide a potential therapeutic strategy for atherosclerosis.