Severity Of Atherosclerotic Lesions Research Articles

Nanobodies as Diagnostic and Therapeutic Tools for Cardiovascular Diseases (CVDs).

The aim of this review is to summarize some of the most recent work in the field of cardiovascular disease (CVD) diagnosis and therapy, focusing mainly on the role of nanobodies in the development of non-invasive imaging methods, diagnostic devices, and advanced biotechnological therapy tools. In the context of the increased number of people suffering from CVDs due to a variety of factors such as sedentariness, poor nutrition, stress, and smoking, there is an urgent need for new and improved diagnostic and therapeutic methods. Nanobodies can be easily produced in prokaryotes, lower eukaryotes, and plant and mammalian cells, and offer great advantages. In the diagnosis domain, they are mainly used as labeled probes that bind to certain surface receptors or other target molecules and give important information on the severity and extent of atherosclerotic lesions, using imaging methods such as contrast-enhanced ultrasound molecular imaging (CEUMI), positron emission tomography (PET), single-photon emission computed tomography coupled with computed tomography (SPECT/CT), and PET/CT. As therapy tools, nanobodies have been used either for transporting drug-loaded vesicles to specific targets or as inhibitors for certain enzymes and receptors, demonstrated to be involved in various CVDs.

Advancing age increases the size and severity of spontaneous atheromas in mouse models of atherosclerosis

Using multiple mouse models, we explored the impact of aging on the size and severity of atherosclerotic lesions. In young, middle-aged and old apolipoprotein E knockout mice (ApoE−/−) fed an atherogenic diet (AD) for 3–8 weeks, plaque/atheroma formation in the descending aorta and aortic root, and atheroma development in the carotid in response to partial carotid ligation (PCL) were assessed. Total and LDL cholesterol, and triglycerides were higher in old compared to both other age groups, regardless of AD duration. Aortic plaque burden increased with AD duration in all ages. The size and plaque morphology grade of aortic root atheromas was higher with age; however, there was no effect of age on the size or severity of carotid atheromas after PCL. We additionally induced hyperlipidemia in young and old C57BL/6 mice by adeno-associated virus mediated upregulation of LDL receptor regulator, Pcsk9, and 5 weeks of AD. Despite lower cholesterol in old compared to young Pcsk9 mice, there was a greater size and severity of aortic root atheromas in old mice. However, like the ApoE−/− mice, there was no effect of age on size or severity of PCL-induced carotid artery atheromas in Pcsk9 mice. Together, these results suggest that aging increases the size and severity of spontaneous aortic atheromas.

Combined glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonism attenuates atherosclerosis severity in APOE*3-Leiden.CETP mice

Background and aimsCombined agonism of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP1R) is superior to single GLP1R agonism in terms of glycemic control and lowering body weight in individuals with obesity and with or without type 2 diabetes mellitus. As both GIPR and GLP1R signaling have also been implicated in improving inflammatory responses and lipid handling, two crucial players in atherosclerosis development, here we aimed to investigate the effects of combined GIPR/GLP1R agonism in APOE*3-Leiden.CETP mice, a well-established mouse model for human-like lipoprotein metabolism and atherosclerosis development. MethodsFemale APOE*3-Leiden.CETP mice were fed a Western-type diet (containing 16% fat and 0.15% cholesterol) to induce dyslipidemia, and received subcutaneous injections with either vehicle, a GIPR agonist (GIPFA-085), a GLP1R agonist (GLP-140) or both agonists. In the aortic root area, atherosclerosis development was assessed. ResultsCombined GIPR/GLP1R agonism attenuated the development of severe atherosclerotic lesions, while single treatments only showed non-significant improvements. Mechanistically, combined GIPR/GLP1R agonism decreased markers of systemic low-grade inflammation. In addition, combined GIPR/GLP1R agonism markedly lowered plasma triglyceride (TG) levels as explained by reduced hepatic very-low-density lipoprotein (VLDL)-TG production as well as increased TG-derived fatty acid uptake by brown and white adipose tissue which was coupled to enhanced hepatic uptake of core VLDL remnants. ConclusionsCombined GIPR/GLP1R agonism attenuates atherosclerosis severity by diminishing inflammation and increasing VLDL turnover. We anticipate that combined GIPR/GLP1R agonism is a promising strategy to lower cardiometabolic risk in humans.

Determining disease response patterns in patients with coronary heart disease

Background. Attitude towards one's own illness significantly affects the course of the disease, the effectiveness of treatment and the possibility of rehabilitation. The formation of certain types of response to the disease determines adherence to treatment.
 Aim. To study the types of attitude to the disease in patients with coronary heart disease, depending on the severity of coronary atherosclerosis and the planned treatment tactics.
 Material and methods. To study the type of patient's response to the disease, a personal questionnaire of the Bekhterev Institute was used. The study included 240 patients with coronary heart disease (150 men and 90 women): the first group 26 people without coronary artery disease; the second group 41 people who were subject to conservative treatment, with hemodynamically unexpressed atherosclerosis of the coronary arteries; the third group 84 patients with severe atherosclerotic lesions of the coronary arteries, who were candidates for surgical revascularization methods; the fourth group 38 people hospitalized for coronary artery stenting; the fifth group 51 people hospitalized for coronary artery bypass grafting. The sixth group was represented by healthy volunteers (40 people). To assess the statistical significance of the differences between the two groups in terms of any parameters with the non-normal distribution of features the MannWhitney test was used. To assess the relationship between two features, the Spearman rank correlation coefficient with an assessment of its significance was used. Differences were considered significant at p 0.05.
 Results. Patients with ischemic heart disease chose statements characteristic of ergopathic and harmonious (p 0.05) types of attitude to the illness. In 56% (p 0.05) of the representatives of the control group, the anosognosic type prevailed. A higher frequency of the euphoric type of attitude towards the disease was found in patients of the second group in comparison with the third one (p=0.009). The fifth group was dominated by sensitive (42.5%) and paranoid (32.5%) types of response; less common were anxious (27.5%) and neurasthenic (30%) ones. A direct correlation was demonstrated between the age of patients and the detectability of hypochondriacal (p=0.027, r=0.15), apathetic (p=0.005, r=0.2) and paranoid (p=0.011, r=0.17) types of attitude towards illness.
 Conclusion. Patients with coronary heart disease have predominantly ergopathic and harmonious types of response, which determine whether they have a sober assessment of their state of health, as well as the significance of work activity for the individual.

Successful laparoscopic cholecystectomy for gallbladder hemorrhage from a Dieulafoy lesion in a patient on hemodialysis: a case report

BackgroundPatients on long-term dialysis are prone to hemorrhagic complications, particularly uremic bleeding, but gallbladder hemorrhage is rare, even in patients on dialysis. There have been occasional reports of a Dieulafoy lesion being a cause of gastrointestinal hemorrhage, but its occurrence within the gallbladder is quite rare. This report describes a case of gallbladder hemorrhage from a Dieulafoy lesion in a patient on hemodialysis that was diagnosed early and successfully treated by laparoscopic cholecystectomy.Case presentationThe patient was a 68-year-old woman on long-term hemodialysis with end-stage renal failure who presented with epigastralgia and back pain. There was no history of trauma or oral administration of antiplatelet or anticoagulant agents. There were no signs of an inflammatory reaction or hyperbilirubinemia. Contrast-enhanced computed tomography revealed a slightly hyperdense area in the distended gallbladder and extravasation within the gallbladder lumen but no gallstones. A severe atherosclerotic lesion was also found. She was diagnosed to have gallbladder hemorrhage and emergency laparoscopic cholecystectomy was performed. Although the postoperative course was complicated by drug fever, she was discharged on postoperative day 10 in a satisfactory condition. Histology revealed hemorrhagic ulceration with an exposed blood vessel accompanied by abnormal arteries in the submucosa. Arteriosclerosis with eccentric intimal hyperplasia in a small-sized artery was also seen. The diagnosis was gallbladder hemorrhage from a Dieulafoy lesion.ConclusionsA Dieulafoy lesion should be kept in mind as a cause of gallbladder hemorrhage in a patient with severe arteriosclerosis and a bleeding diathesis, particularly if on dialysis, and treated as early as possible.

Neutrophil-lymphocyte ratio in patients with coronary heart disease

Introduction. Despite significant advances in the diagnosis and treatment of patients with cardiovascular pathology, it is diseases associated with atherosclerosis that are still the main cause of mortality and disability. Atherosclerosis is based on local inflammation of the vascular wall and disruption of the lipid profile. Neutrophillymphocyte ratio is an indicator that can serve as a new diagnostic criterion of atherosclerotic changes. Materials and methods. The study enrolled 240 patients with coronary heart disease (150 men and 90 women). The subjects gave voluntary informed consent to participate in the study. All patients with CHD underwent coronary angiography, echocardiography and general blood analysis. Statistical processing of the results was performed using "Microsoft Office Excel" for Windows and "Statistica 10.0" software. Mann-Whitney test was used to assess the statistical significance of differences between the two groups for any parameters in the distribution of features other than normal. The Spearman rank correlation coefficient and its significance were used to assess the relationship between the two traits. Results. An increase in NLS values with progression of atherosclerotic coronary lesion severity was found; an inverse correlation between NLS value and LV ejection fraction (EF) was detected. Discussion. Our results, demonstrating an increase in this index with increasing severity of atherosclerotic lesions of the coronary arteries, are consistent with the literature data. Conclusion. Taking into account the fundamental role of inflammation in atherogenesis, as well as the difficulties of routine determination of expensive markers in everyday practice, the inclusion of an uncomplicated and economically affordable index of LVEF to assess the severity of coronary atherosclerosis and stratify the risk of adverse outcomes in patients with CHD is of undoubted scientific and practical interest and dictates the need for further study of its use in various patient cohorts.

Correlation of Epicardial Fat Thickness with Angiographic Severity and LDL Cholesterol Level in CAD

Background: Epicardial fat is independently related to coronary artery disease (CAD). Clinical imaging research has established a robust direct correlation between epicardial fat and abdominal visceral adiposity. This study aimed to assess the association of epicardial fat thickness (EFT) with CAD in patients. Objective: To find the association between EFT, Low-density lipoprotein (LDL) cholesterol levels, and angiographic severity by SYNTAX score. Methods: This prospective observational study involved 321 patients with suspected CAD patients undergoing catheter coronary angiography. Epicardial fat thickness was measured by means of transthoracic echocardiography within 90 days after coronary angiography. The severity of coronary atherosclerotic lesions become evaluated from at least 3 projections in all of the sufferers. The angiographic characteristics of the coronary atherosclerotic lesion have been defined using the SYNTAX score. Results: 321 patients took part in this study; the sex distribution has 259 male subjects (80.7%) and 62 female subjects (19.3%). LDL cholesterol levels <100 mg/dl are present in 75.1% (241 subjects) of the study population. The categories and variables were analyzed, and they show a significant correlation between epicardial fat thickness and SYNTAX score with a p-value of <0.0001. A significant correlation has been observed between LDL cholesterol levels and the angiographic severity of CAD by the SYNTAX score. Conclusion: This study suggests that there is a significant correlation between LDL cholesterol levels, EFT and angiographic severity, and complexity of the coronary lesions by the SYNTAX score. Keywords: Body Fat; Coronary Artery Disease; Epicardial Fat Thickness; CAD

Role of Translationally Controlled Tumor Protein (TCTP) in the Development of Hypertension and Related Diseases in Mouse Models.

Translationally controlled tumor protein (TCTP) is a multifunctional protein that plays a wide variety of physiological and pathological roles, including as a cytoplasmic repressor of Na,K-ATPase, an enzyme pivotal in maintaining Na+ and K+ ion gradients across the plasma membrane, by binding to and inhibiting Na,K-ATPase. Studies with transgenic mice overexpressing TCTP (TCTP-TG) revealed the pathophysiological significance of TCTP in the development of systemic arterial hypertension. Overexpression of TCTP and inhibition of Na,K-ATPase result in the elevation of cytoplasmic Ca2+ levels, which increases the vascular contractility in the mice, leading to hypertension. Furthermore, studies using an animal model constructed by multiple mating of TCTP-TG with apolipoprotein E knockout mice (ApoE KO) indicated that TCTP-induced hypertension facilitates the severity of atherosclerotic lesions in vivo. This review attempts to discuss the mechanisms underlying TCTP-induced hypertension and related diseases gleaned from studies using genetically altered animal models and the potential of TCTP as a target in the therapy of hypertension-related pathological conditions.

Dog models of human atherosclerotic cardiovascular diseases.

Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Eighty-five percent of CVD-associated deaths are due to heart attacks and stroke. Atherosclerosis leads to heart attack and stroke through a slow progression of lesion formation and luminal narrowing of arteries. Dogs are similar to humans in terms of their cardiovascular physiology, size, and anatomy. Dog models have been developed to recapitulate the complex phenotype of human patients and understand the underlying mechanism of CVD. Different methods, including high-fat, high-cholesterol diet and genetic modification, have been used to generate dog models of human CVD. Remarkably, the location and severity of atherosclerotic lesions in the coronary arteries and branches of the carotid arteries of dog models closely resemble those of human CVD patients. Overt clinical manifestations such as stroke caused by plaque rupture and thrombosis were observed in dog models. Thus, dog models can help define the pathophysiological mechanisms of atherosclerosis and develop potential strategy for preventing and treating CVD. In this review, we summarize the progress in generating and characterizing canine models to investigate CVD and discuss the advantages and limitations of canine CVD models.

Therapeutic Intervention with Anti-Complement Component 5 Antibody Does Not Reduce NASH but Does Attenuate Atherosclerosis and MIF Concentrations in Ldlr-/-.Leiden Mice.

Background: Chronic inflammation is an important driver in the progression of non-alcoholic steatohepatitis (NASH) and atherosclerosis. The complement system, one of the first lines of defense in innate immunity, has been implicated in both diseases. However, the potential therapeutic value of complement inhibition in the ongoing disease remains unclear. Methods: After 20 weeks of high-fat diet (HFD) feeding, obese Ldlr-/-.Leiden mice were treated twice a week with an established anti-C5 antibody (BB5.1) or vehicle control. A separate group of mice was kept on a chow diet as a healthy reference. After 12 weeks of treatment, NASH was analyzed histopathologically, and genome-wide hepatic gene expression was analyzed by next-generation sequencing and pathway analysis. Atherosclerotic lesion area and severity were quantified histopathologically in the aortic roots. Results: Anti-C5 treatment considerably reduced complement system activity in plasma and MAC deposition in the liver but did not affect NASH. Anti-C5 did, however, reduce the development of atherosclerosis, limiting the total lesion size and severity independently of an effect on plasma cholesterol but with reductions in oxidized LDL (oxLDL) and macrophage migration inhibitory factor (MIF). Conclusion: We show, for the first time, that treatment with an anti-C5 antibody in advanced stages of NASH is not sufficient to reduce the disease, while therapeutic intervention against established atherosclerosis is beneficial to limit further progression.

Endothelial NCK2 promotes atherosclerosis progression in male but not female Nck1-null atheroprone mice

A better understanding of endothelial dysfunction holds promise for more effective interventions for atherosclerosis prevention and treatment. Endothelial signaling by the non-catalytic region of the tyrosine kinase (NCK) family of adaptors, consisting of NCK1 and NCK2, has been implicated in cardiovascular development and postnatal angiogenesis but its role in vascular disease remains incompletely understood. Here, we report stage- and sex-dependent effects of endothelial NCK2 signaling on arterial wall inflammation and atherosclerosis development. Male and female Nck1-null atheroprone mice enabling inducible, endothelial-specific Nck2 inactivation were fed a high fat diet (HFD) for 8 or 16 weeks to model atherosclerosis initiation and progression, respectively. Analysis of aorta preparations en face during disease progression, but not initiation, showed a significant reduction in plaque burden in males, but not females, lacking endothelial NCK2 relative to controls. Markers of vascular inflammation were reduced by endothelial NCK2 deficiency in both males and females during atherosclerosis progression but not initiation. At advanced stages of disease, plaque size and severity of atherosclerotic lesions were reduced by abrogation of endothelial NCK2 signaling only in males. Collectively, our results demonstrate stage- and sex-dependent modulation of atherosclerosis development by endothelial NCK2 signaling.

Abdominal aortic calcification in patients with inflammatory bowel disease: does anti-tumor necrosis factor α use protect from chronic inflammation-induced atherosclerosis?

Abdominal aortic calcium (AAC) deposition has been suggested as a marker of early atherosclerosis. There is no published data on the evaluation of AAC in inflammatory bowel disease (IBD). AAC was quantified by computed tomography or enterography scans performed in 98 IBD patients and 1:1 age and sex matched controls. AAC deposition was correlated with IBD characteristics, disease activity or severity parameters, laboratory tests and cardiovascular disease (CVD) risk factors. Moderate-severe grade of AAC was found in 35.7% of IBD patients compared to 30.6% of controls (P= 0.544). IBD with CVD and ulcerative colitis patients had significantly higher rates of more severe atherosclerotic lesions (P= 0.001 and P= 0.01, respectively). AAC deposition was similarly distributed in age groups ( < 45, 45-64, and ≥ 65 years) among patients and controls. Multivariate analysis after excluding CVD risk confounders for non-CVD patients found extensive disease (P= 0.019) and lifetime steroids (P= 0.04) as independent risk factors for AAC. Anti-tumor necrosis factor α (TNF-α) use was negatively associated with AAC deposition in non-CVD IBD patients (odds ratio, 0.023; 95% confidence interval, 0.001-0.594; P= 0.023). More than one-third of IBD patients have moderate to severe AAC. Better control of inflammation with anti-TNF-α agents seems to protect IBD patients from ACC deposition and subsequent atherosclerosis.

СООТНОШЕНИЕ ПРОЦЕССОВ СТЕНОЗИРОВАНИЯ И КАЛЬЦИНОЗА В КОРОНАРНЫХ АРТЕРИЯХ У ПАЦИЕНТОВ С ИБС

Abstract. Introduction. Coronary heart disease is one of frequent nosological forms in clinical practice. It is based on atherosclerosis of coronary arteries, main element of which are atherosclerotic plaques. Proliferation of plaques in lumen of vessel leads to its stenosis. Usually coronary atherosclerosis has progressive course, which manifests itself in change in internal composition of plaque. Progression of atherosclerosis is also reflected in increase in degree of calcification of coronary arteries, which can be characterized by degree of calcification. Calcification index is indicator of prevalence and severity of atherosclerotic lesions of coronary bed. Aim. To compare indicators characterizing severity of coronary artery stenosis and calcification according to coronary computed tomography angiography in patients with coronary heart disease. Material and methods. Study included 56 patients. Indicators of calcification of coronary arteries (calcium index of left descending artery, left circumflex artery, right coronary artery, Agatson index), as well as degree of coronary artery stenosis were used. Results and discussion. Degree of calcification was highest in left descending artery, lowest calcification in left circumflex artery, and in right coronary artery calcium index had intermediate value. Regression analysis was used to determine relation of severity of calcification of coronary arteries and degree of their stenosis. Values of these indicators showed significant dependence. In proximal segments of all arteries this dependence is linear. In distal segments of all arteries dependence of stenosis and calcification had form of non-linear regression. Conclusion. Coronary arteries have different severity of calcification: it is most pronounced in left descending artery. Degree of stenosis and calcification demonstrate different variants of relationship depending on artery and segments.

Single-Cell RNA Sequencing Reveals the Pathogenic Relevance of Intracranial Atherosclerosis in Blood Blister-Like Aneurysms.

BackgroundIntracranial non-branching site blood blister-like aneurysms (BBA) are extremely rare and vicious. Their etiology remains elusive, and no molecular study has been carried out to reveal its pathogenic relevance to intracranial atherosclerosis. To investigate its transcriptomic landscape and underlying potential pathogenesis, we performed single-cell RNA sequencing with extensive pathological validation.MethodsIn total, 12,245 cells were recovered for single-cell RNA sequencing analysis from 1 BBA and 2 saccular intracranial aneurysms (IAs). Unbiased clustering using Seurat-based pipeline was used for cellular landscape profiling. Cellchat was used to understand intracellular communications. Furthermore, 10 BBAs and 30 IAs were retrospectively collected for pathological validations like scanning electron microscopy, H&E stain, Masson stain, Verhoeff Van Gielson stain, and immunofluorescence.ResultsSingle-cell transcriptome profiled 14 total subclusters in 6 major groups, namely, 6 monocyte/macrophage clusters, 2 T&NK clusters, 3 vascular smooth muscle cell (VSMC) clusters, 1 dendritic cell, 1 B cell, and 1 endothelial cell cluster. The only mural cell identified in BBAs was VSMC-2 cluster, while mural cells in IAs comprise most clusters of VSMCs and endothelial cells. Upregulated genes in BBA-derived VSMCs are related to arterial mineralization and atherosclerosis, such as PTX3, SPP1, LOX, etc., whereas vasodilation and physiological regulatory genes such as MGP, ACTA2, and MYL9 were conversely enriched in conventional IA-derived VSMCs. Immune cells in the BBA were predominantly macrophages, with a low fraction of T&NK cells, while conventional IAs had a higher percentage of T&NK. Gene enrichment analysis suggested that macrophages in BBA were highly enriched in lipid metabolism as well as atherosclerosis. Ligand–receptor interaction suggested that secretory phosphoprotein 1 (also known as osteopontin) played a major role in mediating the intracellular communication between VSMC and macrophages, especially in BBA. Pathological experiments corroborate with the bioinformatic findings and further characterized BBAs as a thin-walled thrombotic aneurysm with severe atherosclerotic lesions, where ApoE+ macrophages and OPN+ mural cells are intimately involved in the inflammation process.ConclusionsThe preexisting intracranial atherosclerosis might predispose the parent artery to the pathogenic occurrence of BBAs. These data shed light on the pathophysiology of intracranial aneurysms and might assist in the further resolution of the complexity in aneurysm pathogenesis.

Serum Cytokines Predict the Severity of Coronary Artery Disease Without Acute Myocardial Infarction.

IntroductionVarious cytokines were involved in the process of atherosclerosis, and their serum levels were correlated with coronary artery disease (CAD) to varying degrees. However, there were limited reports about the correlation between serum cytokines and the severity of coronary atherosclerotic lesion in patients with non-acute myocardial infarction (AMI). The purpose of this study was to investigate the relationship between serum cytokines and the severity of CAD, and identify the predictors of severe CAD in patients suspected to have CAD but AMI had been ruled out.MethodsA total of 502 patients who had suspected CAD and underwent coronary angiography were enrolled. The serum levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, TNF-α, IFN-α,and IFN-γ were determined by multiplexed particle-based flow cytometric assays technology. And the severity of CAD was evaluated by Gensini score (GS).ResultsThe serum levels of IL-4, IL-12p70, IL-17, and IFN-α were significantly lower in the severe CAD group (GS≥30) than those in the non-severe CAD group (GS < 30). And IL-12p70 and IL-17 were negatively correlated with the severity of CAD. Multivariate logistic regression analyses demonstrated that two serum cytokines (IL-12p70 and IL-17), one clinical protective factor (HDL-C), and two clinical risk factors (gender and diabetes) were the independent predictors of severe CAD. ROC curve analysis showed that multivariate mode combined these predictors had a good performance in predicting severe CAD.ConclusionThe combination of serum cytokines (IL-12p70 and IL-17) and clinical risk factors (HDL-C, gender, and diabetes) may help identify patients with more severe coronary artery lesions from those with suspected CAD but not AMI, and may contribute to guiding the risk stratification for patients with chest discomfort in health care facilities without sufficient medical resources (especially cardiac catheterization resources).

Abstract 450: Monocyte-to-endothelial Cell Crosstalk By 27-hydroxycholesterol Promotes Monocyte Vascular Recruitment And Thereby Advances Atherogenesis

How hypercholesterolemia invokes the vascular inflammation that is critical to atherogenesis is poorly understood. Sterol 27-hydroxylase (cyp27a1) converts cholesterol to 27-hydroxycholesterol (27HC), and we previously showed that 27HC is an estrogen receptor alpha (ERα) ligand. Here we determined how 27HC produced by monocytes impacts atherogenesis. In the absence of changes in circulating lipids, monocyte cyp27a1 deletion in apolipoprotein E -/- mice (apoE -/- ) caused a 35% decline in atherosclerotic lesion severity; this was related to decreased macrophage accumulation due to a reduction in lesion monocyte recruitment, which likely occurred as a result of decreases in endothelial cell VCAM-1 and ICAM-1. Experiments in cultured endothelial cells revealed that 27HC liganding of ERα activates NF-κB by causing the disassociation of the cytoplasmic scaffolding protein septin 11 from ERα and resulting septin 11 activation of Jnk kinase signaling. Endothelial septin 11 deletion in apoE -/- mice phenocopied the impact of monocyte cyp27a1 loss, yielding a 37% decrease in lesion severity that was similarly explained by declines in endothelial cell VCAM-1 and ICAM-1, lesion monocyte recruitment and macrophage accumulation. In bone marrow transplant studies the reintroduction of monocyte cyp27a1 caused a 71% increase in lesions which was fully dependent on endothelial cell ERα and septin 11. Furthermore, in apoE -/- mice pharmacologic inhibition of cyp27a1 decreased lesion severity by 41% without altering circulating lipids, causing declines in endothelial cell VCAM-1 and ICAM-1, monocyte recruitment and macrophage accumulation. There was no additivity with monocyte cyp27a1 deletion and cyp27a1 inhibition, indicating that the treatment-related atheroprotection occurs via monocyte cyp27a1 inhibition. These cumulative findings reveal that through a unique pro-inflammatory mechanism involving endothelial cell ERα and septin 11, monocyte-to-endothelial cell crosstalk by the cholesterol metabolite 27HC promotes monocyte vascular recruitment to advance atherogenesis. Interventions attenuating the crosstalk may complement LDL-directed strategies in the battle against atherosclerosis.

Biomarkers of non-specific inflammation and atherosclerosis of carotid arteries in obstructive sleep apnea syndrome

Purpose of study. Identification of significant laboratory markers for the development of atherosclerosis (AS) of the carotid arteries (CA) in patients with obstructive sleep apnea syndrome (OSAS).Materials and methods. 152 male patients were examined, 84 of whom, according to polysomnography (PSG), were diagnosed with OSAS. Diagnosis of AS CA was performed by triplex scanning. The complex of laboratory studies included the assessment of lipid metabolism, the concentration of highly sensitive C-reactive protein (hsCRP), interleukin‑1β (IL‑1β), interleukin‑6 (IL‑6) and interleukin‑10 (IL‑10) in blood serum.Results. In patients with OSAS, a statistically significant increase in the complex of proatherogenic factors was found: hsCRP, pro-inflammatory cytokines, ratio of apoproteins and atherogenic coefficient compared with patients without OSAS despite the absence of differences in the severity of atherosclerotic lesions of the carotid arteries in these groupsConclusion. The development of OSAS is associated with severe lipid metabolism disorders and activation of nonspecific inflammation, which determines an increased risk of atherosclerosis in this group of patients.

The severity of coronary artery defeat in coronary heart disease patients with different variants of the vitamin D receptor gene and the level of vitamin D sufficiency

Introduction. Vitamin D deficiency may be an independent predictor of coronary heart disease (CHD) and the severity of coronary atherosclerosis. The results of studies of the association of various polymorphisms of the vitamin D receptor (VDR) gene with the risk and severity of CHD are contradictory, which necessitates the study of genetic variants of the VDR gene and the characteristics of the clinical course of CHD in the Russian population.The objective was to determine the distribution of genotypes of TaqI, BsmI and ApaI of polymorphic variants of the VDR gene and the level of vitamin D sufficiency in CHD patients with varying severity of CHD, residents of St. Petersburg.Methods and materials. The study included 407 CHD patients and 318 patients without clinical signs of CHD of comparable age (p&gt;0.05). All CHD patients underwent coronary angiography. Typing of the VDR gene variants was performed by polymerase chain reaction and subsequent restriction analysis. Determination of the level of 25(OH)D blood serum was carried out by enzyme immunoassay.Results. Vitamin D deficiency was detected in 82 % of CHD patients, the content of 25(OH)D in blood serum was lower in CHD patients who had 2 or more myocardial infarctions (MI) than in those who had one MI (p=0.03). Vitamin D deficiency is associated with a 3.6-fold increased risk of multivessel disease (p=0.01). The presence of the aa genotype and the a allele (ApaI), the bb genotype and the b allele of the VDR gene (BsmI) is associated with an increased risk of CHD and the severity of atherosclerotic lesions of the coronary arteries.Conclusion. Vitamin D deficiency is typical for CHD patients and is associated with the severity of coronary atherosclerosis. The presence of aa genotype and a allele (ApaI polymorphism), bb genotype and b allele of the VDR gene (BsmI polymorphism) is associated with an increased risk of CHD and the severity of atherosclerotic lesions of the coronary arteries. TaqI polymorphism of the VDR gene is not associated with the risk of CHD.

Endurance exercise ameliorates Western diet\u2013induced atherosclerosis through modulation of microbiota and its metabolites

The World Health Organization determined cardiovascular disease to be the leading cause of death globally; atherosclerosis is the primary cause of the high morbidity and mortality rates. Regular physical activity is an effective strategy for maintaining endothelial health and function to prevent the development of atherosclerosis. Obesity is also a crucial risk factor for atherosclerotic progression in combination with various complications and systemic inflammation. Physiological homeostasis is modulated by the intestinal microbiota, but the mechanisms through which exercise attenuates atherosclerosis through the microbiota have not been elucidated. Therefore, we investigated the effects of endurance exercise on atherosclerosis induced by a Western diet (WD) and apolipoprotein E (ApoE) knockout in terms of microbiota parameters and metabolites. Genetically modified ApoE knockout mice (C57BL/6-Apoeem1Narl/Narl, ApoEKO) and wild-type mice (C57BL6/J) were divided into the following four groups (n = 6), namely, wild-type mice fed a chow diet (WT CD), ApoEKO mice fed a chow diet (ApoE CD), ApoEKO mice fed a WD (ApoE WD), and ApoEKO mice fed a WD and performing endurance exercise (ApoE WD EX), for a 12-week intervention. The WD significantly induced obesity and atherosclerotic syndrome in the ApoE WD group. Severe atherosclerotic lesions and arterial thickness were significantly elevated and accompanied by increases in VCAM-1, MCP-1, TNF-α, and IL-1β for immune cell chemotaxis and inflammation during atherosclerotic pathogenesis in the ApoE WD group. In addition, dysbiosis in the ApoE WD group resulted in the lowest short-chain fatty acid (SCFA) production. Endurance exercise intervention (ApoE WD EX) significantly alleviated atherosclerotic syndrome by reducing obesity, significantly inhibiting VCAM-1, MCP-1, TNF-α, and IL-1β expression, and increasing the production of SCFAs. Modulation of the microbiota associated with inflammation, such as Desulfovibrio, Tyzzerella, and Lachnospiraceae_ge, and increased SCFA production, particularly through an abundance of Rikenellaceae and Dubosiella, were also observed after exercise intervention. Endurance exercise can alleviate WD-induced atherosclerosis through the amelioration of obesity, inflammation, and chemotaxis signaling, which are modulated by the microbiota and derived SCFAs.

Prevalence of Erectile Dysfunction in Patients With Abdominal Aortic Aneurysm: An Exploratory Study.

IntroductionErectile dysfunction (ED) is defined as the recurrent inability to achieve and maintain a satisfactory erection for sexual intercourse. Many studies have highlighted that ED shares common cardiovascular risk factors with cardiovascular disease. No data are reported about the prevalence of ED in patients with the abdominal aortic aneurysm (AAA). The aim of our study was to investigate the preoperative information given about sexual functions of patients undergoing endovascular aneurysm repair (EVAR) and to compare it with the presence and severity of steno-occlusive atherosclerotic lesions of the pelvic arterial tree at pre-operative Computed Tomography Angiography (CTA).MethodsWe prospectively enrolled all men patients who underwent elective EVAR from September to November 2021. Preoperative ED was evaluated using the International Index of Erectile Function (IIEF-5) questionnaire. Preoperative imaging was routinely performed with CTA scan of the abdominal aorta and iliac-pelvic district. An innovative score of pelvic arterial disease associated to AAA was defined, dividing the iliac district in 4 zones attributing a grading of severity for each zone bilaterally (score ranges 0–24). Linear regression analysis was used to correlate IIEF-5 score to anatomical score of pelvic arterial steno-occlusive disease.ResultsA total of 25 patients were enrolled. Median age was 74 ± 5.3 years. IIEF-5 average score was 14.8 ± 7.1. Eight cases (32%) had severe ED; one case (4%) had moderate, five patients (20%) had mild to moderate ED; five patients (20%) had mild ED, and 6 (24%) patients had no ED. CTA evaluation revealed an average anatomical score of 7.9 ± 4.5. Pelvic disease was considered moderate-severe in 20 cases (80%) and not significant in 20% (five cases). Linear regression analysis confirmed the hypothesis that a more diseased pelvic arterial tree was correlated to a more severe ED (Y = −1.531* × + 26.35 [slope CI: −1.946 to −1.117, p < 0.0001]).ConclusionAlthough typically unreported, the prevalence of ED associated to AAA was found to be high. A vasculogenic origin of ED in patients with AAA is plausible and may be easily confirmed by the evaluation of pelvic arterial distribution at angio-CT performed for EVAR planning. Our proposed “MAPPING AND SCORING SHEET” may help to identify the vasculogenic origin of ED in AAA patients.