Severity Of Atherosclerotic Lesions Research Articles

Features of atherosclerotic lesions of the coronary arteries in patients with myocardial infarction and concomitant newly diagnosed hypothyroidism

Objective: to assess the incidence of newly diagnosed subclinical and manifest hypothyroidism in patients with ST-segment elevation myocardial infarction (STEMI) and to identify angiographic features of coronary artery lesions in this combined pathology.Materials and methods: in all patients with STEMI, the level of thyroid-stimulating hormone (TSH) was determined, and thyroid function was assessed if the TSH level deviated from the norm. Stage I of the study included 441 patients, stage II included 133 patients with STEMI. Depending on the presence of newly diagnosed hypothyroidism, patients were divided into 3 groups: 1st — patients without hypothyroidism (n = 57), 2A group — with subclinical hypothyroidism (n = 42) and 2B group — with manifest hypothyroidism (n = 34). All patients underwent coronary angiography and percutaneous coronary intervention.Results: newly diagnosed hypothyroidism occurred in 27.44% of patients with STEMI: subclinical — in 19.73%, manifest — in 7.7% of cases. Patients with concomitant overt hypothyroidism had significantly more severe atherosclerotic lesions of the coronary arteries compared to patients without hypothyroidism.Conclusion: a high incidence of newly diagnosed hypothyroidism in patients with STEMI was established (27.44% of cases). Multivessel coronary lesions were recorded more often in patients with overt hypothyroidism than in patients with subclinical hypothyroidism and without hypothyroidism.

The Blood Plasma Lipidomic Profile in Atherosclerosis of the Brachiocephalic Arteries.

According to the World Health Organization, ischemic stroke is the second leading cause of death in the world. Frequently, it is caused by brachiocephalic artery (BCA) atherosclerosis. Timely detection of atherosclerosis and its unstable course can allow for a timely response to potentially dangerous changes and reduce the risk of vascular complications. Omics technologies allow us to identify new biomarkers that we can use in diagnosing diseases. This research included 90 blood plasma samples. The study group comprised 52 patients with severe atherosclerotic lesions BCA, and the control group comprised 38 patients with no BCA atherosclerosis. Targeted and panoramic lipidomic profiling of their blood plasma was carried out. There was a statistically significant difference (p < 0.05) in the values of the indices saturated fatty acids (FAs), unsaturated FAs, monounsaturated FAs, omega-3, and omega-6. Based on the results on the blood plasma lipidome, we formed models that have a fairly good ability to determine atherosclerotic lesions of the brachiocephalic arteries, as well as a model for identifying unstable atherosclerotic plaques. According only to the panoramic lipidome data, divided into groups according to stable and unstable atherosclerotic plaques, a significant difference was taken into account: p value < 0.05 and abs (fold change) > 2. Unfortunately, we did not observe significant differences according to the established plasma panoramic lipidome criteria between patients with stable and unstable plaques. Omics technologies allow us to obtain data about any changes in the body. According to our data, statistically significant differences in lipidomic profiling were obtained when comparing groups with or without BCA atherosclerosis.

Apolipoprotein O modulates cholesterol metabolism via NRF2/CYB5R3 independent of LDL receptor

Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in mice. Hepatic APOO expression was increased in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (Apoo−/−) model, it was found that APOO depletion aggravated diet-induced obesity and elevated plasma cholesterol levels. Upon crossing with low-density lipoprotein receptor (LDLR) and apolipoprotein E (APOE) knockout hyperlipidemic mouse models, Apoo−/−Apoe−/− and Apoo−/−Ldlr−/− mice exhibited elevated plasma cholesterol levels, with more severe atherosclerotic lesions than littermate controls. This indicated the effects of APOO on cholesterol metabolism independent of LDLR and APOE. Moreover, APOO deficiency reduced cholesterol excretion through bile and feces while decreasing phospholipid unsaturation by inhibiting NRF2 and CYB5R3. Restoration of CYB5R3 expression in vivo by adeno-associated virus (AAV) injection reversed the reduced degree of phospholipid unsaturation while decreasing blood cholesterol levels. This represents the first in vivo experimental validation of the role of APOO in plasma cholesterol metabolism independent of LDLR and elucidates a previously unrecognized cholesterol metabolism pathway involving NRF2/CYB5R3. APOO may be a metabolic regulator of total-body cholesterol homeostasis and a target for atherosclerosis management.Apolipoprotein O (APOO) regulates plasma cholesterol levels and atherosclerosis through a pathway involving CYB5R3 that regulates biliary and fecal cholesterol excretion, independently of the LDL receptor. In addition, down-regulation of APOO may lead to impaired mitochondrial function, which in turn aggravates diet-induced obesity and fat accumulation.

Prognostic value of leukocyte-glycemic index in long-term evolution of diabetic patients with peripheral arterial disease following endovascular treatment

Abstract Objective: The aim of this article is to determine the predictive value of the leukocyte-glycemic index in the long-term evolution of diabetic patients with peripheral arterial disease following endovascular treatment. Methods: This retrospective observational study enrolled 127 diabetic patients diagnosed with peripheral arterial disease requiring endovascular treatment. Patients were categorized into two groups based on the severity of the infrapopliteal atherosclerotic lesions identified during the pre-operative Computer Tomography Angiography examination. Group 1 includes patients without severe damage to the infrapopliteal artery, while Group 2 includes patients with severe infrapopliteal artery damage, identified by stenosis greater than 70% on all infrapopliteal arteries. The primary outcome was to assess the association between leukocyte-glycemic index value at baseline and the severity of infrapopliteal atherosclerotic lesions and long-term major amputation after percutaneous transluminal angioplasty. Results: Patients in Group 2 had a higher incidence of cardiovascular events (p=0.009), stage IV Leriche-Fontaine (p=0.016), and incidence of major amputation (p&lt;0.001), as well as an increased value of leukocyte-glycemic index (p=0.004). During the follow-up, patients with above-median leukocyte-glycemic index value have a higher risk of major amputation (p=0.034), as seen in the Kaplan-Meier analysis. Moreover, at cox-regression, elevated biomarker values were associated with long-term risk of major amputation, independent of age, sex, cardiovascular risk factors, and below-the-knee arterial occlusion (HR:2.69, p=0.001). Conclusions: Elevated values of leukocyte-glycemic index are associated with the severity of infrapopliteal atherosclerotic lesions and major amputation in the long term.

Sex-Age Interplay Among Young Aged Egyptians With First Acute Myocardial Infarction.

The burden of modifiable risk factors in young Egyptian adults presenting with first acute myocardial infarction (AMI), sex differences, sex-age interplay, and its relationship with demographic, angiographic characteristics, and type of AMI is a good topic for discussion. The study enrolled 165 young (≤45 years old) consecutive, eligible patients diagnosed with first AMI (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction), for their demographic, angiographic, echocardiographic, and laboratory investigations and gender differences. Our population were 29-45 years old and 12.1% were females, most of whom had ST-elevation myocardial infarction; obesity in females and smoking in males were the most prevalent; and the younger the age of females presenting with AMI the more aggressive underlying risk factors and the more reduction in left ventricular ejection fraction. Most of the female culprit lesions were thrombotic and the severity of atherosclerotic culprit lesions correlated positively with blood pressure. The age paradox in young females (regarding left ventricular ejection fraction and the traditional risk factors) and the thrombotic nature of the culprit lesion mandate early intensive 1-year and 2-year preventive strategies against coronary heart disease (CHD) with special concern for obesity as the main trigger early in life with proper control of blood pressure. In males, smoking cessation programs are the main target to ameliorate the progress of CHD hand in hand with the other 1-year and 2-year preventive strategies of CHD.

Ultrasound Carotid Plaque Score and Severity of Coronary Artery Disease Assessed by Computed Tomography Angiography in Patients with Arterial Hypertension.

The aim of the study was to assess the relationship between the presence of atherosclerotic lesions in the carotid arteries detected by ultrasound and the occurrence of atherosclerosis in the coronary arteries determined by computed tomography (CT) in patients with arterial hypertension (HTA). A total of 83 patients with HTA were qualified for the study (age: 71.3 ± 8.5 years). All subjects underwent carotid arteries ultrasound and coronary arteries CT. The carotid plaque score was assessed using ultrasound. The studied group was divided into two subgroups: a subgroup with the carotid plaque score ≤ 1 (A) and a subgroup with carotid plaque score ≥2 (B). Coronary arteries CT assessed coronary artery calcium score (CACS) and degree of coronary stenosis based on CAD-RADS. In subgroup B, a significantly higher CACS (411.3 ± 70.1 vs. 93.5 ± 31.8) and significantly higher grade in the CAD-RADS classification were demonstrated than in subgroup A (CAD-RADS ≥ 3: 21.8 vs. 6.0%). The regression analysis showed that carotid plaque score and age are independent risk factors for the severity of atherosclerotic lesions in the coronary arteries. In summary, ultrasound assessment of the carotid plaque score in patients with HTA could be considered as surrogate indicator of the risk and severity of atherosclerotic changes in the coronary arteries, but further studies are necessary to corroborate these results.

Unveiling the oral-gut connection: chronic apical periodontitis accelerates atherosclerosis via gut microbiota dysbiosis and altered metabolites in apoE−/− Mice on a high-fat diet

The aim of this study was to explore the impact of chronic apical periodontitis (CAP) on atherosclerosis in apoE−/− mice fed high-fat diet (HFD). This investigation focused on the gut microbiota, metabolites, and intestinal barrier function to uncover potential links between oral health and cardiovascular disease (CVD). In this study, CAP was shown to exacerbate atherosclerosis in HFD-fed apoE−/− mice, as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining. 16S rRNA sequencing revealed significant alterations in the gut microbiota, with harmful bacterial species thriving while beneficial species declining. Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis, leading to elevated levels of taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and tauroursodeoxycholic acid (TDCA). These metabolic shifts may contribute to atherosclerosis development. Furthermore, impaired intestinal barrier function, characterized by reduced mucin expression and disrupted tight junction proteins, was observed. The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions, highlighting the importance of the intestinal barrier in cardiovascular health. In conclusion, this research underscores the intricate interplay among oral health, gut microbiota composition, metabolite profiles, and CVD incidence. These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues, as well as the need for further investigations into the intricate mechanisms linking oral health, gut microbiota, and metabolic pathways in CVD development.

Atherosclerosis: an overview of mouse models and a detailed methodology to quantify lesions in the aortic root.

Cardiovascular disease, the primary cause of human mortality globally, is predominantly caused by a progressive disorder known as atherosclerosis. Atherosclerosis refers to the process of accumulation of cholesterol-enriched lipoproteins and the concomitant initiation of inflammatory processes in the arterial wall, including the recruitment of immune cells. This leads to the formation of atherosclerotic plaques, initially causing a thickening of the arterial wall and narrowing of arteries. However, as plaque formation progresses, atherosclerotic plaques may become unstable and rupture, leading to a blood clot that blocks the affected artery or travels through the blood to block blood flow elsewhere. In the early 1990s, emerging gene editing methods enabled the development of apolipoprotein E knockout (Apoe-/- ) and low-density lipoprotein receptor knockout (Ldlr-/- ) mice. These mice have been instrumental in unraveling the complex pathogenesis of atherosclerosis. Around the same time, human APOE*3-Leiden transgenic mice were generated, which were more recently cross-bred with human cholesteryl ester transfer protein (CETP) transgenic mice to generate APOE*3-Leiden.CETP mice. This model appears to closely mimic human lipoprotein metabolism and responds to classic lipid-lowering interventions due to an intact ApoE-LDLR pathway of lipoprotein remnant clearance. In this review, we describe the role of lipid metabolism and inflammation in atherosclerosis development and highlight the characteristics of the frequently used animal models to study atherosclerosis, with a focus on mouse models, discussing their advantages and limitations. Moreover, we present a detailed methodology to quantify atherosclerotic lesion area within the aortic root region of the murine heart, as well as details required for scoring atherosclerotic lesion severity based on guidelines of the American Heart Association adapted for mice.

The Gensini Score System is a Useful Tool in Assessing the Burden and Severity of Coronary Artery Atherosclerotic Lesions [Letter

The Gensini Score System is a Useful Tool in Assessing the Burden and Severity of Coronary Artery Atherosclerotic Lesions [Letter

Активность теломеразы, гиперлипидемия и особенности атеросклеротического поражения брахиоцефальных артерий у бессимптомных пациентов трудоспособного возраста с субклиническим гипотиреозом

Aim. To study telomerase activity, lipidemia and to assess the severity of atherosclerotic lesions of the brachiocephalic arteries in asymptomatic patients of working age with subclinical hypothyroidism. Design. A cross-sectional cohort study. Materials and methods. Data on 131 patients of working age (32 men and 99 women) with different hormonal status of the thyroid gland (thyroid) without clinical signs of chronic cerebral circulatory insufficiency were analyzed. Based on the assessment of the hormonal status of the thyroid gland, 2 groups of patients were formed: 87 with laboratory-confirmed hypertension (thyroid-stimulating hormone level &gt; 4.0 mMU/l with normal characteristics of free fractions of thyroid hormones) and 44 patients without thyroid dysfunction. The groups formed were comparable in age, gender composition, presence and severity of hypertension, aggravated family history of early cardiovascular events, and smoking. All patients underwent ultrasound examination of the brachiocephalic arteries, determination of the lipid spectrum and telomerase concentration. The processing of the obtained data was carried out using statistical packages Excel, Statistica v. 10.0. The data obtained were interpreted as reliable, and the differences between the indicators were considered significant when the error-free prediction value was equal to or greater than 95% (p &lt; 0.05). Results. In the group of people with hypothyroidism, the proportion of people with multivessel atherosclerotic lesion was higher (34.5% (n = 30) vs. 13.6% (n = 6) (χ2 = 6.37; p &lt; 0.05)), one or a combination of several signs of instability of atherosclerotic plaque (41.4% (n = 36) vs. 18.2% (n = 8) (χ2 = 7.05; p &lt; 0.01)). In patients with subclinical hypothyroidism, precerebral atherosclerosis occurs against the background of atherogenic type IIa secondary hyperlipidemia (67.8% (n = 59) vs. 34.1% (n = 6) (χ2 = 13.52; p &lt; 0.001) in combination with insufficiency of antiatherogenic high density lipoproteins (74.7% (n = 65) vs. 45.5% (n = 20) (χ2 = 10.98; p &lt; 0.001)), lower values of telomerase concentration in comparison with the group of people without thyroid dysfunction: (8.2 (7.4–9.5) vs. 10.8 (10.1–12.2) ng/ml (p &lt; 0.001)). The relationship between the level of telomerase activity (r = –0.72; p &lt; 0.05) and the presence of subclinical hypothyroidism, atherosclerotic lesions of the precerebral bed in patients (r = –0.33; p &lt; 0.05) was established. Conclusion. In clinically healthy patients of working age with newly diagnosed, medically uncorrected subclinical hypothyroidism, the proportion of persons with ultrasound signs of multivessel atherosclerotic lesions of the brachiocephalic arteries is higher, and precerebral atherosclerosis occurs against the background of atherogenic type IIa secondary hyperlipidemia in combination with insufficiency of antiatherogenic high density lipoproteins, lower values of telomerase activity in comparison with the group of persons without thyroid dysfunction. Etiopathogenetic mechanisms of "early vascular aging", the criteria for stratification of risk groups for atherosclerosis-associated cardiovascular disease, the choice of diagnostic algorithms for visualizing preclinical stages of atherogenesis, and timely antiatherogenic tactics in asymptomatic patients with comorbid thyroid pathology require further study. Verification of a stenosing hemodynamically significant or non-hemodynamically significant atherosclerotic lesion of the coronary basin, regardless of the clinical component, is a factor of high cardiovascular risk requiring immediate correction of hyperlipidemia. Keywords: thyroid gland, hypothyroidism, hyperlipidemia, atherosclerosis, precerebral (brachiocephalic) arteries, telomerase activity, comorbid pathology.

Correlation of Serum Endocan Level With Apoptosis Indicators and Severity of Atherosclerotic Lesions of Coronary Arteries in Patients With Coronary Heart Disease.

Aim To study the relationship of blood serum concentration of endocan with indexes of apoptosis and clinical and instrumental characteristics of patients with ischemic heart disease (IHD).Material and methods The study included 176 subjects (105 men and 71 women). 150 of them were diagnosed with IHD and 26 were healthy volunteers. Anthropometric measurements, coronary angiography, echocardiography, duplex ultrasound scanning of extracranial parts of the brachiocephalic arteries were performed for all patients. Concentrations of endocan (ng / ml), glucose (mmol / l), and apoptotic markers Bcl-2 (ng / ml), Bax (ng / ml), Bcl-2 / Bax, TRAIL (pg / ml), and p53 (ng / ml) were measured in blood serum. Patients were divided into groups based on their SYNTAX scores: group 1 with moderate atherosclerotic lesions of the coronary arteries (CA) (score &lt; 22, 78 patients); group 2 with severe CA atherosclerosis (score 23-32, 37 patients); and group 3 with extremely severe CA lesions (score &gt;33, 35 patients). The control group consisted of healthy volunteers (26 subjects). All groups were age- and sex-matched. Differences were considered statistically significant at p&lt;0.05.Results A correlation was found between endocan concentration and IHD severity (r=0.32, p&lt;0.001). In group 1, the median endocan concentration was 14.57 ng / ml [8.21; 23.66], in group 2, 19.34 ng / ml [8.425; 26.645], in group 3, 32.13 ng / ml [18.2; 39.12], and in the control group, 6.92 ng / ml [4.62; 9.18]. Correlations of varying strength and significance were observed between the endocan concentration and a number of clinical and instrumental characteristics. Endocan concentrations significantly differed in groups of patients with multifocal atherosclerosis (p&lt;0.01), angina pectoris (p&lt;0.01), a history of myocardial infarction (p&lt;0.001), and obesity (p&lt;0.05) from patients without these signs. Also, a correlation was found between serum endocan concentration and apoptotic markers: TRAIL (r= -0.448, p&lt;0.001); BCL-2 (r= -0.552, p&lt;0.001), Bax (r= -0.519, p&lt;0.001), Bcl-2 / Bax (r= -0.576, p&lt;0.001) and p53 (r= -0.520, p &lt;0.001).Conclusion The study demonstrated a potential role of endocan as a promising biomarker for risk stratification, prognosis and therapeutic monitoring of IHD patients.

Correlation analysis of central arterial pressure parameters and the severity of atherosclerotic lesions in coronary arteries: A retrospective study.

To investigate the correlation between central arterial pressure (CAP) parameters and the severity of atherosclerotic lesions in the coronary arteries, understand the value of CAP in assessing the risk of coronary heart disease (CHD), and provide a theoretical basis for the prevention and treatment of CHD. Between January 2021 and January 2022, 224 patients admitted to our hospital for complete coronary angiography (CAG) were included in this retrospective study. CAP parameters, including central systolic pressure (CSP), diastolic pressure (CDP), and pulse pressure (CPP), and Gensini scores were collected; the association between CAP parameters and the severity of coronary lesions was analyzed using the Pearson correlation coefficient (r) and multivariate regression analysis. CPP was significantly higher in the coronary multi-branch lesion group than in the single-branch lesion group in patients with CHD (P < .05). CSP, CDP, and CPP were significantly higher in the high Gensini score group than in the low Gensini score group for coronary vascular lesions; furthermore, CSP and CPP were significantly higher in the high Gensini score group than in the medium Gensini score group (P < .05). Pearson correlation analysis showed that CSP and CPP were positively and CDP was negatively correlated with the severity of coronary artery lesions in patients with CHD (P < .05). Logistic regression analysis showed that a history of diabetes, CSP, CDP, and CPP were independent risk factors for severe atherosclerotic lesions in the coronary arteries (P < .05). noninvasive CAP-related indices, such as CSP, CDP, and CPP, are independently correlated with and can be used to predict the severity of coronary lesions in patients with CHD, which may be beneficial for guiding clinical diagnosis and treatment.

Activation of GPBAR1 attenuates vascular inflammation and atherosclerosis in a mouse model of NAFLD-related cardiovascular disease

While patients with nonalcoholic fatty liver disease (NAFLD) are at increased risk to develop clinically meaningful cardiovascular diseases (CVD), there are no approved drug designed to target the liver and CVD component of NAFLD. GPBAR1, also known as TGR5, is a G protein coupled receptor for secondary bile acids. In this study we have investigated the effect of GPBAR1 activation by BAR501, a selective GPBAR1 agonist, in Apolipoprotein E deficient (ApoE−/−) mice fed a high fat diet and fructose (Western diet), a validated model of NAFLD-associated atherosclerosis. Using aortic samples from patients who underwent surgery for abdominal aneurism, and ex vivo experiments with endothelial cells and human macrophages, we were able to co-localize the expression of GPBAR1 in CD14+ and PECAM1+ cells. Similar findings were observed in the aortic plaques from ApoE-/- mice. Treating ApoE-/- mice with BAR501, 30 mg/kg for 14 weeks, attenuated the body weight gain while ameliorated the insulin sensitivity by increasing the plasma concentrations of GLP-1 and FGF15. Activation of GPBAR1 reduced the aorta thickness and severity of atherosclerotic lesions and decreased the amount of plaques macrophages. Treating ApoE-/- mice reshaped the aortic transcriptome promoting the expression of anti-inflammatory genes, including IL-10, as also confirmed by tSNE analysis of spleen-derived macrophages. Feeding ApoE-/- mice with BAR501 redirected the bile acid synthesis and the composition of the intestinal microbiota. In conclusion, GPBAR1 agonism attenuates systemic inflammation and improve metabolic profile in a genetic/dietetic model of atherosclerosis. BAR501 might be of utility in the treatment for NAFLD-related CVD.

Triglyceride-glucose index is associated with severe obstructive coronary artery disease and atherosclerotic target lesion failure among young adults

BackgroundEarly diagnosis and treatment effectiveness of early-onset coronary artery disease (EOCAD) are crucial, and non-invasive predictive biomarkers are needed for young adults. We aimed to evaluate the usefulness of the triglyceride-glucose (TyG) index, a novel marker of insulin resistance, in identifying young CAD patients and predicting their risk of developing target lesion failure (TLF).MethodsWe recruited EOCAD patients (luminal narrowing ≥ 70%) and controls free from CAD (luminal narrowing < 30%), both aged 45 years or younger, from 38 hospitals in China between 2017 and 2020. EOCAD patients who underwent successful percutaneous coronary intervention were followed for incident TLF. TyG index was defined as Ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. We used logistic regression and Cox proportional hazards modeling to evaluate the association of TyG index with prevalent EOCAD and incident TLF, respectively. The discriminatory ability of TyG index was assessed by the area under the receiver-operating characteristic curve (AUC).ResultsAmong the included 1513 EOCAD patients (39.6 ± 4.4 years, 95.4% male) and 1513 age-matched controls (39.0 ± 4.4 years, 46.4% male), TyG index was positively associated with the prevalence of EOCAD (adjusted odds ratio: 1.40, 95% confidence interval [CI] 1.23–1.60, per standard deviation [SD] increase in TyG index). The addition of TyG index to an empirical risk model provided an improvement in diagnostic ability for EOCAD, with a net reclassification improvement of 0.10 (95% CI 0.03–0.17, p = 0.005). During a medium of 33 month (IQR: 31–34 months) follow-up, 43 (3.3%) patients experienced TLF. Multivariate Cox regression model revealed that TyG index was an independent risk factor for TLF (adjusted hazard ratio [HR]: 2.410, 95% CI 1.07–5.42 comparing the top to bottom TyG index tertile groups; HR: 1.30, 95% CI 1.01–1.73, per SD increase in TyG index). Compared with a model of conventional risk factors alone, the addition of the TyG index modestly improved the AUC (0.722–0.734, p = 0.04) to predict TLF.ConclusionsTyG index is positively associated with prevalent EOCAD and incident TLF. TyG index appeared to be a valuable component of future efforts to improve CAD risk stratification and TLF outcome prediction among young adults.

The role of coronary artery calcium estimation in the primary prevention strategy for cardiovascular diseases

Calcification is one of the stages of complicated and uncomplicated atherosclerotic plaque development. Determination of calcium deposits in the composition of plaques by the method of multispiral computer tomography allows to assess the coronary atherosclerotic lesion severity. The advantages of the test include a relatively wide availability, low cost and dose of ionizing radiation, as well as no need to inject a contrast agent. Calculation of the coronary artery calcium (CAC) according to the Agatston method is the “gold standard” for quantitative assessment of the coronary atherosclerosis severity. The review highlights modern ideas about the role of the test in primary prevention in people without diagnosed cardiovascular disease. Methodological principles of determining coronary calcium are explained. The principles of test result interpretation and presentation based on the international СAC-RADS scale are described. Data from population studies on the prevalence of coronary calcification in people without cardiovascular disease in different age categories are provided. The results of the prognostic value of CAC based on the analysis of large population studies are presented. The prognostic value of a negative test (CAC = 0) for coronary calcium is discussed. Data are presented on the recommended frequency of repeated examinations in patients with CAC = 0 depending on an individual cardiovascular risk. The data of randomized clinical trials on the expediency of determining coronary calcium in certain age categories are given. The place of the test in international clinical recommendations for the primary prevention of cardiovascular diseases is analyzed. Research findings on a personalized approach to prescribing statins and aspirin based on coronary calcium test results are discussed. Data are provided on improved adherence in patients with coronary calcium screening compared with the standard approach. The limitations and shortcomings of the test are analyzed separately, among which the impossibility of controlling the effectiveness of hypolipidemic therapy with statins in dynamics can be identified. An integrated approach to the role of the coronary calcium test based on the analysis of current international clinical recommendations is provided.

Blockade of CXCR4 promotes macrophage autophagy through the PI3K/AKT/mTOR pathway to alleviate coronary heart disease

ObjectiveAutophagy is important in regulating inflammation and cholesterol efflux, suggesting that targeting autophagy may slow down atherosclerosis (AS). Since the pathological basis of coronary artery disease (CAD) is atherosclerosis, it is crucial to investigate the role of autophagy in atherosclerosis. This study aimed to investigate the role of the chemokine CXC chemokine receptor 4 (CXCR4) in promoting macrophage autophagy through the phosphoinositide-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway to alleviate coronary artery disease. MethodsThe human left coronary artery and myocardium were collected to detect CXCR4, MAP1LC3(LC3) and SQSTM1(p62) expression. ApoE−/− mice were used to establish an atherosclerosis mice model, while human monocytes (THP-1) were used to establish a foam cell model and co-cultured with foam cells using siRNACXCR4. Western blotting was conducted to quantify CXCR4, PI3K/AKT/mTOR pathway protein, LC3, Beclin1 and p62 protein levels. The left coronary artery from humans and mouse aorta and myocardium were stained with Hematoxylin and Eosin (H&E), macrophages with Oil Red O staining and foam cells were assessed by Movat's staining. CXCR4 levels, PI3K/AKT/mTOR pathway protein, LC3 and p62 were detected by immunohistochemistry (IHC) and immunofluorescence assays. Detection of autophagosomes in macrophages using transmission electron microscopy. We further assessed whether the effect of CXCR4-mediated macrophage autophagy on the formation of atherosclerosis and structural changes in the myocardium was mediated via the PI3K/AKT/mTOR signaling pathway. ResultsCXCR4 and p62 proteins were upregulated in human coronary lesions, mouse aorta, myocardial tissue, and foam cells, while LC3II/LC3I was downregulated. p85 (P-PI3K), Ser473 (P-AKT), and Ser2448 (P-mTOR) phosphorylated proteins associated with the PI3K/AKT/mTOR pathway were detected in AS and foam cell models. Upregulated CXCR4 inhibited autophagy of macrophages and increased the severity of atherosclerotic lesions. After specific knockdown of CXCR4 by adeno-associated virus (AAV9-CXCR4-RNAi) and siRNACXCR4, the above indicators were reversed, macrophage autophagy was promoted, the severity of atherosclerotic lesions was reduced, and the disorganized arrangement of myocardial architecture was improved. ConclusionKnockdown of CXCR4 reduces the extent of coronary artery disease by promoting macrophage autophagy through the PI3K/AKT/mTOR pathway to attenuate atherosclerosis.

The Comparison of Coronary Angiographic Profile between Diabetic and Non-Diabetic Patients with Coronary Artery Disease in a Nepalese Population

Background: Diabetes mellitus is associated with an increase in cardiovascular morbidity and mortality. As the prevalence of diabetes mellitus is increasing globally the burden of death related to cardiovascular disease including myocardial infarction will be a great burden to countries like Nepal. The aim is to compare the extent and severity of coronary artery disease between diabetic and non-diabetic patients referred for coronary angiography.&#x0D; Materials and methods: It was a Hospital-based, cross-sectional study conducted in the Department of Internal medicine, BPKIHS Dharan, Nepal. All consecutive patients undergoing coronary angiography with a clinical indication for the procedure during the study period of one year were included in the study. 61 subjects with diabetes were compared with 147 subjects without diabetes for assessing the severity and extent of coronary artery disease. The coronary atherosclerosis score was used to grade the severity of lesions visualized by coronary angiography.&#x0D; Results: The mean coronary atherosclerosis score was 6.64±4.18 among diabetes and 4.97±4.07 among the non-diabetic group with p-value of 0.008 which was statistically significant. The left anterior descending coronary artery was significantly more frequently involved in diabetics than nondiabetic patients 88.52% vs. 66.67% (p&lt;0.002).&#x0D; Conclusion: Diabetic patients had more severe and extensive atherosclerotic lesions in coronary arteries than the non-diabetic patients on coronary angiography suggesting atherosclerotic burden in the diabetes population is higher in our population.

Differential effects of plant and animal fats on obesity-induced dyslipidemia and atherosclerosis in Ldlr-/-.Leiden mice.

Cardiovascular disease (CVD) is closely associated with obesity through risk factors such as dyslipidemia and chronic low-grade inflammation, which may be affected by diet. Dietary fats have been extensively studied in relation to CVD risk, however these studies have not always yielded consistent results, most likely due to lack in control of experimental conditions and confounding factors. Here we studied the effects of different plant and animal fats on dyslipidemia, inflammation, and atherosclerosis. Ldlr-/-.Leiden mice were fed isocaloric energy-dense diets with translational macronutrient composition for 28 weeks. The diets were identical apart from the type of fat they contained: either (1) a mixture of olive and rapeseed oil, (2) sunflower oil, (3) pork fat, (4) beef fat, or (5) milk fat. The fatty acid composition of the diets was determined and effects on circulating lipid and inflammatory risk factors and atherosclerosis were examined, complemented by adipose tissue histology and liver transcriptomics. While visceral fat mass, adipocyte size, and adipose tissue inflammation were not differentially affected by the diets, atherosclerotic lesion load and severity was more pronounced with increasing dietary saturated fatty acid content and decreasing monounsaturated and polyunsaturated fatty acid content, and hence most pronounced with beef and milk fat. These differential effects were accompanied by increases in pro-atherogenic plasma lipids/lipoproteins (e.g., triglycerides, apolipoprotein B), activation of pro-atherogenic cytokine/chemokine signaling pathways in liver, and with circulating pro-atherogenic mediators of inflammation altogether providing a rationale for the differential effects of plant and animal fats.

The interventional effect of Polygonatum cyrtonema Hua polysaccharide on atherosclerosis in mice of different sexes

In the present study, we investigated the intervention effects of a purified Polygonatum cyrtonema polysaccharide (PCP) on high-fat diet (HFD)-induced atherosclerosis in male and female LDLr−/− mice. Results showed that HFD caused severe dyslipidemia, atherosclerotic lesions, oxidative damages and inflammation in male and female mice, and these effects seemed to be more pronounced in males than in females. However, the above variations could be dose-dependently reversed by PCP treatment, and the intervention effects on males were greater than those on females. Nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPKs) and protein kinase B (Akt) are 3 pivotal signaling pathways mediating the development of atherosclerosis. Consistently, PCP was also found to significantly decrease the phosphorylation of p65, p38, extracellular-regulated kinase 1/2 (ERK1/2) and Akt, and increase the protein expression of inhibitor of NF-κB (IκB) in the aortas of male and female mice induced by HFD. Taken together, these findings indicated that PCP could be effective for the prevention of atherosclerosis, and the intervention effect of PCP on male mice was more obvious than that of female mice.

Oridonin supplementation attenuates atherosclerosis via NLRP-3 inflammasome pathway suppression.

Atherosclerosis, a long-term inflammatory and immune condition affecting medium- and large-sized arteries, results in the thickening of artery walls and the accumulation of inflammatory cells and fatty streaks that establish fibrous capsules with macrophages at the site of injury. Atherosclerosis has a major impact on the pathogenesis of cardiovascular diseases. Oridonin has been shown to exclusively inhibit the NLRP3 inflammasome without affecting the activation of AIM-2 or NLRC-4 inflammasomes. The current study aimed to evaluate how adding Oridonin to a diet impacts the onset of atherosclerosis. Twenty-one male rabbits weighing 1.5 to 2.0 kg were included in the study. The rabbits were kept in controlled environmental conditions and divided into three groups: a normal control group fed a conventional chow diet, an atherogenic control group fed a high-cholesterol diet (2% cholesterol-rich), and an Oridonin-treated group (Ori) fed an atherogenic diet supplemented with Oridonin (20 mg/kg) administered orally once daily. Compared to animals on a normal diet, an atherogenic diet was associated with a statistically significant (p=0.001) increase in the mean expression of the NLRP3 inflammasome mRNA. The Oridonin-treated group showed a statistically significant (p=0.001) decline in the mean expression of NLRP3 inflammasome mRNA compared to the atherogenic group. Furthermore, the initial atherosclerotic lesion in the group treated with Oridonin was statistically (p=0.001) less severe compared to the atherogenic group. Finally, Ori treated group had significantly (p≤0.001) lower IL-1B immunostaining intensity than the atherogenic group (mean rank 14.5,25 respectively). The study concluded that Oridonin supplementation resulted in less severe initial atherosclerotic lesions, likely due to the suppression of NLRP3 inflammasome and the anti-inflammatory effect through the downregulation of IL1B expression.