Process Of Atherosclerosis Research Articles

MO751OXIDATIVE STRESS IN PATIENTS WITH CHRONIC RENAL FAILURE AND CARDIOVASCULAR COMPLICATIONS

Abstract Background and Aims The atherosclerosis process is highly accelerated in patients with chronic kidney disease (CKD). Oxidative stress is considered as one of the pro-atherogenic factors involved in accelerating the atherosclerosis process of the carotid artery. The aim of the present study was to determine the relationship between oxidative stress markers and the progression of carotid atherosclerosis in CKD patients. Method The study was conducted on 220 patients with CKD and 40 controls, and the disease stage was scored between 2 and 5D. Blood samples were taken and myeloperoxidases, malondialdehyde, nitric oxide, glutathione, and oxidised low-density lipoprotein were measured. Furthermore, we studied the correlations between these biomarkers and clinical and para-clinical cardiovascular complications. Results The average age of patients was 60.5 years. The oxidative stress markers average ± SD levels in CKD groups compared to the control were as follows: myeloperoxidase (49.89 ±1.98 vs. 38.45 ±1.98 UI/ml), malondialdehyde (5.2 ±0.12 vs. 3.26 ±0.03 µmol/l), nitric oxide (56.82 ±1.06 vs. 42.19 ±2.1 µmol/l), glutathione (42.21 ±1.3 vs. 79.4 ±2.6 IU/ml), and oxLDL (15.57 ±1.07 vs. 1.72 ±0.82 µmol/l). While the glutathione level decreased significantly in advanced CKD stage (p < 0.05), the concentrations of all the other biomarkers increased significantly in accordance with CKD score (p < 0.05). Patients with high IMD (> 1 mm) had higher values of the prooxidant markers (NO, oxLDL, MDA, MPO) but lower antioxidant marker values (glutathione), compared to other patients with lower IMD Conclusion Cardiovascular diseases, mainly atherosclerosis, can be diagnosed indirectly by measuring oxidative stress markers. Furthermore, theses markers can be used to predict the progression of CKD, for better management of the disease.

Ischemia Modified Albumin as a Novel Biochemical Indicator in Peripheral Artery Patients

Objective: Peripheral artery disease (PAD) is the name given to blocked blood flow in major arteries other than cerebral and coronary circulation. The diagnosis and treatment of PAD is very important because of the high frequency of PAD. In this study, it was aimed to investigate the possible change in next generation oxidative stress-antioxidant status indicators as a biochemical parameter that may be useful in the diagnosis and follow-up of PAD. Method: Forty healthy controls and 40 male and female patients with peripheral artery disease who applied to the Alanya Alaaddin Keykubat University Research and Training Hospital were enrolled in the study on a voluntary basis. Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), ischemia modified albumin (IMA) and Thiol balance were studied with the colorimetric method. Results: The TOS (p <0.001), OSI (p <0.001), IMA (p = 0.027), total thiol (0.004) levels were higher in the peripheral artery patients compared to the control group, while the TAS (p <0.001) and native thiol / total thiol ratio (index 3) (p = 0.018) values ​​were significantly lower. Conclusion: The increase in TOS and IMA levels may be used as an indicator of peripheral artery disease. There is an increase in inflammation in the ischemia and atherosclerosis processes. An ischemia-specific protein called ischemia-modified albumin may be used as a rapid and practical laboratory marker in common peripheral artery disease.

Age and Interleukin-15 Levels Are Independently Associated With Intima-Media Thickness in Obesity-Related NAFLD Patients.

Common carotid intima-media thickness (IMT) represents a functional and structural marker of early, precocious, and subclinical atherosclerosis, independently from the carotid plaque. Macrophage cells, which have been detected in adipose tissue and atherosclerotic plaques, are regulated by interleukin-15 (IL-15). At the light of the conflicting results concerning the role of IL-15 in atherosclerosis, the aim of the study was to retrospectively evaluate in a population of 80 obese patients, with median age of 46 years (IQR 34–53 years), with a low rate of comorbidities but with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS), the relationship between IMT and serum concentrations of IL-15. Anthropometric measures, metabolic profile, and serum inflammatory markers, as well as the levels of IL-15, MCP-1, b FGF, and GM-CSF, were analyzed by a bead-based assay. IMT, HS, subcutaneous, and visceral adipose tissues were detected by ultrasonography. The IL-15 levels of the obese patients were increased with respect to those of 44 young healthy subjects, i.e., 2.77 (1.21–4.8) vs. 1.55 (1–2.4) pg/mL (P = 0.002). In the univariate analysis, IL-15 levels were associated to IMT and to those of MCP-1, b FGF, and GM-CSF, without any relation to other inflammatory markers such as CRP and ferritin, except fibrinogen. In the multivariate analysis, after adjusting the HS severity for the extent of visceral adiposity, a dramatic change in prediction of IMT by HS was shown (β from 0.29 to 0.10, P from 0.008 to 0.37). When the visceral adipose tissue was combined with IL-15, on the one hand, and the well-known coronary artery disease (CAD) risk factors—i.e., age, gender, smoking status, HDL-cholesterol concentrations, triglycerides levels, and HOMA—on the other, only age and IL-15 remained the predictors of IMT (β = 0.60, P = 0.0001 and β = 0.25, P = 0.024, respectively). There was no association of IL-15 with various anthropometric parameters nor with body fat distribution and severity of HS, also after adjusting for age. Age is resulted to be the main factor in the prediction of IMT and thus of early atherosclerosis. The prediction of IMT by IL-15 coupled with the lack of prediction by the well-known CAD risks is in agreement with recent data, which emphasizes the main role of the immune system in the onset/worsening of atherosclerosis, even though the role of visceral adiposity should be further deepened. Age and IL-15 levels were both predictors of early atherosclerosis in this population of obese patients with NAFLD, suggesting a possible role of this cytokine in the atherosclerosis process.

Acute effects of cigarette smoke on Endothelial Nitric Oxide synthase, vascular cell adhesion molecule 1 and aortic intima media thickness

Background. Cigarette smoking could induce endothelial dysfunction and the increase of circulating markers of inflammation by activation of monocytes. This can lead to increased intima media thickness (IMT) of entire blood vessels and result in acceleration of the atherosclerosis process. However, to our knowledge, little is known about the role of cigarette smoking in this atherosclerotic inflammatory process. The aim of this study is to explore the link between cigarette smoking and its effect on endothelial nitric oxide synthase (e-NOS) and vascular cell adhesion molecule 1 (VCAM-1). Methods. An experimental study with a post-test only controlled group design was used. We used 18 Wistar rats (Rattus norvegicus) randomly subdivided into two groups: group K (-) were not exposed to tobacco smoke, whereas group K (+) were exposed to smoke equivalent of more than 40 cigarettes for 28 days daily. After 28 days, samples were analyzed for e-NOS, VCAM-1 and aortic IMT. Results. Our results indicate that tobacco smoke can enhance the expression of VCAM-1 on rat cardiac vascular endothelial cells, resulting in a decreased expression of e-NOS level and increase of aortic IMT. Linear regression model found that eNOS level negatively correlated wiith aortic IMT (r2 = 0.584, β = -0.764, p &lt; 0.001), whereas VCAM-1 expression did not correlate with aortic IMT (r2 = 0.197, p = 0.065). Conclusion. Low e-NOS level and high VCAM-1 level observed after cigarette smoke exposure which may increase aortic IMT.

Lipid transfer to high-density lipoprotein is greater in elderly individuals with higher predictive cardiorespiratory fitness for age

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): FAPESP and CNPq Background Elderly individuals have higher coronary artery disease (CAD) risk. Triggering factors include diminished peak of oxygen consumption (VO2peak), commonly referred as cardiorespiratory fitness (CF), and increase in atherogenic lipid profile: non high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). The effect of aging on HDL-C is yet not clear, however, evaluating only the concentrations do not represent all HDL anti-atherosclerosis potential, aspects related to HDL metabolism and function can be more accurate to understand atherosclerosis process. Beyond that, elderly individuals also show reduced lipid transfer to HDL, an important assessment of HDL metabolism and function reported to be lower in CAD patients. Additionally, higher CF level is associated with longevity and lower hospitalizations rates and higher lipid transfer, independently of HDL-C. Data about different ages and absolute values of CF on lipids transfer are nonexistent. Purpose: To analyze the effect of paired CF absolute values and BMI in a healthy population of different ages on lipid transfer to HDL. Methods: 61 healthy individuals, enrolled in two groups: 30 young (27 ± 4 years, 21 females, BMI: 24.6 ± 2.6 kg/m², VO2peak: 33.9 ± 5.0 ml/kg/min) and 31 elderly (67 ± 5 years, 15 females, BMI: 23.9 ± 3.3 kg/m², VO2peak: 33.2 ± 4.5 ml/kg/min) that do not use any medication for chronic disease. Anthropometric data were collected. All participants performed treadmill cardiopulmonary test and the CF predictive value for age was calculated, according to each sex. Plasma lipids and cholesterol ester transfer protein (CETP) concentrations were determined. Lipid transfer was performed by incubating plasma with a donor lipoprotein-like nanoparticle containing radioactively labeled unesterified cholesterol (UC) and esterified cholesterol (EC), followed by chemical precipitation and radioactive count. Cholesterol transfers from the donor nanoparticle to HDL are expressed as %. For the statistical analysis Student"s t and Mann-Whitney tests were used according to data distribution. Results: Waist circumference (p = 0.0291) and waist-hip ratio (p &amp;lt; 0.0001) were higher in elderly. LDL-C (p = 0.0005) and non HDL-C (p = 0.0003) were higher in elderly, as well apolipoprotein A-I, B, and CETP concentration. HDL-C and triglycerides were equal between groups. EC (p = 0.0268) and UC (p = 0.0348) transfers to HDL were higher in elderly. VO2peak predictive by age expressed in percentage was higher in elderly (90 ± 13 vs. 120 ±18; p &amp;lt; 0.0001). Conclusion: Elderly individuals show higher anthropometric data and concentrations of atherogenic cholesterol lipoproteins; however, HDL-C was equal. When paired by absolute CF values and BMI with young adults, elderly subjects with high CF predicted by age, have higher cholesterol transfer to HDL which demonstrates greater HDL metabolism.

LncRNA AK087124/miR-224-5p/PTEN axis modulates endothelial cell injury in atherosclerosis through apoptosis and AKT signaling pathway

Noncoding RNAs (ncRNAs) have been shown to play important roles in atherosclerosis-related endothelial cells dysfunction during atherosclerosis processes. In the study, our purpose was to discover new long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) via competitively interacting each other to regulate the pathogenesis process of atherosclerosis. We investigated the roles of lncRNA AK087124 and miR-224-5p in atherosclerotic pathogenesis and found that AK087124 was up-regulated while miR-224-5p was down-regulated in in the plasma and plaque from atherosclerotic mice compared with normal mice. Ox-LDL was used to establish the mouse aorta endothelial cell (MAEC) injury model. The function study indicated that knockdown of AK087124 inhibited ox-LDL induced endothelial apoptosis and inflammatory response. Bioinformatic prediction combining with luciferase assays indicated that AK087124 could sponge miR-224-5p and enhance the PTEN expression which is a target of miR-224-5p. RNA pull down assays also showed that biotin-miR-224-5p probe could interacted directly with AK087124 and PTEN. Pearson correlation analysis further demonstrated that AK087124 and PTEN expression are negatively correlated with miR-224-5p. Rescue study revealed that miR-224-5p silencing and PTEN overexpression both can reverse the effect of AK087124 on the ox-LDL induced endothelial injury. These data indicated that AK087124 and miR-224-5p could be potential biomarkers and target molecules to treatment and diagnosis for atherosclerosis.

Contrast-enhanced ultrasound molecular imaging of activated platelets in the progression of atherosclerosis using microbubbles bearing the von Willebrand factor A1 domain.

Platelet-endothelial interactions have been linked to increased inflammatory activation and a prothrombotic state in atherosclerosis. The interaction between von Willebrand factor (vWF)-A1 domain and platelet glycoprotein (GP) Ib/IX plays a significant role in mediating the adhesion of platelets to the injured endothelium. In the present study, contrast-enhanced ultrasound (CEU) molecular imaging with microbubbles bearing the vWF-A1 domain was performed to non-invasively monitor activated platelets on the vascular endothelium in the procession of atherosclerosis. A targeted CEU contrast agent was prepared by attaching the vWF-A1 domain to the shell of microbubbles (MbA1). Rat isotype control antibody was used to produce control (Mbctrl) microbubbles. The binding of MbA1 and Mbctrl to activated platelets was assessed in in vitro flow chamber experiments. Apolipoprotein E (ApoE-/-) deficient mice were studied as a model of atherosclerosis. At 8, 16 and 32 weeks of age, CEU molecular imaging of the proximal aorta with MbA1 and Mbctrl was performed and the imaging signals from microbubbles were quantified. Atherosclerotic lesion severity and platelets on the endothelial surface were assessed by histology and immunohistochemistry. In in vitro flow chamber studies, attachment of MbA1 to activated platelets on culture dishes was significantly greater than that of Mbctrl across a range of shear stresses (P<0.05). The attachment of Mbctrl was sparse and not related to the aggregated platelets. As lesion development progressed in the ApoE-/- mice, molecular imaging of activated platelets demonstrated selective signal enhancement of MbA1 (P<0.05 vs. Mbctrl) at all ages. Selective signal enhancement from MbA1 increased from 8 to 32 weeks of age. Immunohistochemistry for GPIIb revealed the presence of platelets on the endothelial cell surface in each group of ApoE-/- mice and that the degree of platelet deposits was age-dependent. The results of the present study indicated that non-invasive CEU molecular imaging with targeted microbubbles bearing the vWF-A1 domain could not only detect activated platelets on the vascular endothelium but also indicate lesion severity in atherosclerosis.

Цукровий діабет і артеріальна гіпертензія

В огляді проведений аналіз літературних джерел, присвячених сучасному стану проблеми цукрового діабету (ЦД) і артеріальної гіпертензії (АГ). За даними Всесвітньої організації охорони здоров’я, АГ та ЦД 2-го типу після ожиріння є одними з провідних чинників серцево-судинного ризику, які найбільш поширені серед населення світу. За останні 30 років поширеність АГ зменшилась до однієї четвертої частини населення світу, але захворюваність на ЦД зросла з 4,7 до 8,5%, і прогноз на майбутнє свідчить про подальший драматичний приріст. Покращення обізнаності, лікування та контролю цих захворювань є основною метою глобальної системи охорони здоров’я. Поширеність АГ у хворих на ЦД 2-го типу до трьох разів вища, ніж у пацієнтів без ЦД, а поєднання АГ і ЦД суттєво збільшує ймовірність розвитку серцево-судинних захворювань. Несприятливий взаємозв’язок цих двох станів, прискорюючи процеси атеросклерозу, може спричинити негативні патофізіологічні зміни серцево-судинної системи. Крім того, відомо, що кардіоваскулярна автономна нейропатія, яка виникає в результаті пошкодження вегетативних нервових волокон, що іннервують серце та судини, є вагомим ускладненням ЦД 2-го типу, особливо за наявності системної АГ. Зокрема, аналізуються питання, пов’язані із спільними патофізіологічними механізмами, основними системними та метаболічними чинниками, що можуть сприяти коморбідності ЦД і АГ. Наведені класифікація, особливості діагностики АГ, особливості оцінки ураження органів, опосередкованого АГ. Аналізуються питання, пов’язані з основними підходами до лікування артеріальної гіпертензії при цукровому діабеті; використанням блокаторів ренін-ангіотензинової системи, блокаторів кальцієвих каналів, тіазидних і тіазидоподібних діуретиків, блокаторів бета-адренергічних рецепторів, альфа-адреноблокаторів, антагоністів мінералокортикоїдних рецепторів; особливостями комбінованої терапії та лікування резистентної артеріальної гіпертензії.

Experimental study on alleviating atherosclerosis through intervention of mitochondrial calcium transport and calcium-induced membrane permeability transition

To investigate the effort of mitochondrial calcium transport and calcium-induced membrane permeability transition in alleviating atherosclerosis. The experimental mice were divided into three groups: the control group (C57BL/6 mice with...

Hydroxytyrosol Acetate Inhibits Vascular Endothelial Cell Pyroptosis via the HDAC11 Signaling Pathway in Atherosclerosis.

Hydroxytyrosol acetate (HT-AC), a natural polyphenolic compound in olive oil, exerts an anti-inflammatory effect in cardiovascular diseases (CVDs). Pyroptosis is a newly discovered form of programmed inflammatory cell death and is suggested to be involved in the atherosclerosis (AS) process. However, the effect of HT-AC on vascular endothelial cell pyroptosis remains unknown. Thus, we aimed to investigate the effect of HT-AC on vascular endothelial cell pyroptosis in AS and related signaling pathways. In vivo studies showed that HT-AC alleviated the formation of atherosclerotic lesions and inhibited pyroptosis in the aortic intima of ApoE−/− mice fed a high-fat diet (HFD) for 12 weeks. In vitro, we found that HT-AC treatment of human umbilical vein endothelial cells (HUVECs) alleviated tumor necrosis factor-alpha (TNF-α)-induced pyroptosis by decreasing the number of PI positive cells, decreasing the enhanced protein expressions of activated caspase-1 and gasdermin D (GSDMD), as well as by decreasing the release of pro-inflammatory interleukin (IL)-1β and IL-6. Besides, HT-AC down-regulated HDAC11 expression in the aortic intima of HFD-fed ApoE−/− mice and TNF-α-stimulated HUVECs. To determine the underlying mechanism of action, molecular docking and drug affinity responsive target stability (DARTS) were utilized to identify whether HDAC11 protein is a target of HT-AC. The molecular docking result showed good compatibility between HT-AC and HDAC11. DARTS study's result showed that HDAC11 protein may be a target of HT-AC. Further study demonstrated that knockdown of HDAC11 augmented the inhibition of HT-AC on pyroptosis in TNF-α-stimulated HUVECs. These findings indicate that HT-AC might prevent vascular endothelial pyroptosis through down-regulation of HDAC11 related signaling pathway in AS.

The Relationship Between Nutrition and Atherosclerosis.

Atherosclerosis is the basic pathological process of many diseases, such as coronary atherosclerosis and stroke. Nutrients can affect the occurrence and development of atherosclerosis. At present, in nutrition science, the research on atherosclerosis focuses on which nutrients play an important role in its prevention strategy, and what are the possible mechanisms of its action. In the current study, the process of atherosclerosis can be affected by adjusting the proportion of nutrients in the diet. In this review, we pay attention to the effects of phytosterols, omega-3-polyunsaturated fatty acids, polyphenol, vitamin, and other nutrients on atherosclerosis, pay attention to their current epidemiological status, current nutritional research results, and prevention or a possible mechanism to reduce the risk of development of atherosclerosis. So that more personalized nutritional approaches may be more effective in terms of nutritional intervention responses to atherosclerosis.

Extracellular-vesicle containing miRNA-503-5p released by macrophages contributes to atherosclerosis.

Endothelial dysfunction, and the differentiation of smooth muscle cells (SMCs) into proliferative, secretory phenotypes, are two major pathophysiological processes in atherosclerosis. SMCs have the potential to recruit macrophages in atherosclerotic plaques, in which macrophages drive inflammatory responses. In this study, we found that microRNA-503-5p (miR-503-5p) was enriched in either extracellular vesicles (EVs), secreted by oxidized low-density lipoprotein-treated macrophages, or the EVs from peripheral blood mononuclear cells of atherosclerosis patients. miR-503-5p was transferred intercellularly from macrophages to the co-cultured human coronary artery endothelial cells (HCAECs) and HCASMCs via EVs, thus reducing the proliferative and angiogenic abilities of HCAECs and accelerating the proliferative and migrating abilities of HCASMCs. Smad family members 1, 2 and 7 were negatively regulated by miR-503-5p in HCAECs and HCASMCs. miR-503-5p was verified as an enhancer of inflammatory cytokines and adhesion molecules released by macrophages, in part via the down-regulation of smad family members 1, 2 and 7. The inhibition of miR-503-5p by lentivirus reduced atherosclerotic lesion formations in the aorta of atherosclerotic mice. Our work demonstrated a miR-503-5p- and EV-mediated mechanism for macrophage communication with HCAECs and HCASMCs in atherosclerosis. miR-503-5p is pro-atherosclerotic stimuli that may be a therapeutic target for atherosclerosis treatment.

Identification and functional analysis of a biflavone as a novel inhibitor of transient receptor potential vanilloid 4-dependent atherogenic processes

Atherosclerosis, a chronic inflammatory disease of large arteries, is the major contributor to the growing burden of cardiovascular disease-related mortality and morbidity. During early atherogenesis, as a result of inflammation and endothelial dysfunction, monocytes transmigrate into the aortic intimal areas, and differentiate into lipid-laden foam cells, a critical process in atherosclerosis. Numerous natural compounds such as flavonoids and polyphenols are known to have anti-inflammatory and anti-atherogenic properties. Herein, using a fluorometric imaging plate reader-supported Ca2+ influx assay, we report semi high-throughput screening-based identification of ginkgetin, a biflavone, as a novel inhibitor of transient receptor potential vanilloid 4 (TRPV4)-dependent proatherogenic and inflammatory processes in macrophages. We found that ginkgetin (1) blocks TRPV4-elicited Ca2+ influx into macrophages, (2) inhibits oxidized low-density lipoprotein (oxLDL)-induced foam cell formation by suppressing the uptake but not the binding of oxLDL in macrophages, and (3) attenuates oxLDL-induced phosphorylation of JNK2, expression of TRPV4 proteins, and induction of inflammatory mRNAs. Considered all together, the results of this study show that ginkgetin inhibits proatherogenic/inflammatory macrophage function in a TRPV4-dependent manner, thus strengthening the rationale for the use of natural compounds for developing therapeutic and/or chemopreventive molecules.

HIV-Infected Naïve Patients Exhibit Endothelial Dysfunction Concomitant with Decreased Natural Antibodies Against Defined Apolipoprotein B Autoantigens.

Fundamento:Fatores de risco definidos para HIV e tradicionais podem estar associados a um aumento de eventos cardiovasculares. Estudos recentes sugerem que a resposta imune humoral à LDL modificada pode estar associada ao processo de aterosclerose.Objetivos:Avaliar a presença de anti-LDL oxidada e de peptídeos derivados da Apolipoproteína B no sangue, bem como sua associação à função endotelial na infecção por HIV.Métodos:Este estudo incluiu consecutivamente sujeitos com idade, sexo e dados demográficos correspondentes em dois grupos: (1) indivíduos infectados com HIV e naïve para terapia antiviral e (2) indivíduos não infectados. A aterosclerose subclínica foi avaliada pela espessura íntima-média, utilizando-se a ultrassonografia das artérias carótidas. A função endotelial foi determinada pela dilatação mediada por fluxo (DMF) da artéria braquial por ultrassonografia. Os níveis de autoanticorpos (IgM, IgG) de lipoproteínas de baixa densidade antioxidadas (LDL-ox), fragmentos de peptídeos antiapolipoproteína B (peptídeos ApoB-D e 0033G-Cys), e citocina foram avaliados por meio de ELISA.Resultados:Os resultados deste estudo não mostraram diferenças na aterosclerose subclínica entre os grupos. Entretanto, os sujeitos infectados com HIV apresentaram uma DMF mais baixa, em comparação com os sujeitos não infectados. Portanto, os sujeitos infectados com HIV apresentaram níveis mais altos de citocinas inflamatórias, títulos de IgG anti-LDL-ox, e IgG anti-ApoB-D. Em contraste, títulos de IgM anti-ApoB-D foram mais baixos em indivíduos infectados com HIV e associados a funções endoteliais diminuídas.Conclusões:Os resultados deste estudo mostram que a infecção por HIV, em sujeitos naïve, está associada à disfunção endotelial e à diminuição de anticorpos naturais para antígenos Apo-B.

Role of PI3K in the Progression and Regression of Atherosclerosis.

Phosphatidylinositol 3 kinase (PI3K) is a key molecule in the initiation of signal transduction pathways after the binding of extracellular signals to cell surface receptors. An intracellular kinase, PI3K activates multiple intracellular signaling pathways that affect cell growth, proliferation, migration, secretion, differentiation, transcription and translation. Dysregulation of PI3K activity, and as aberrant PI3K signaling, lead to a broad range of human diseases, such as cancer, immune disorders, diabetes, and cardiovascular diseases. A growing number of studies have shown that PI3K and its signaling pathways play key roles in the pathophysiological process of atherosclerosis. Furthermore, drugs targeting PI3K and its related signaling pathways are promising treatments for atherosclerosis. Therefore, we have reviewed how PI3K, an important regulatory factor, mediates the development of atherosclerosis and how targeting PI3K can be used to prevent and treat atherosclerosis.

Aspirin Resistance as a Result of Impaired Interaction of Platelets and Neutrophils in Patients with Coronary Heart Disease

Aim. To study the relationship between the levels of synthesis of reactive oxygen species (ROS) by platelets and neutrophils in patients with coronary heart disease (CHD) before and after coronary artery bypass grafting (CABG), depending on sensitivity to acetylsalicylic acid (ASA).Material and methods. The study included 95 patients with coronary artery disease who are indicated for CABG surgery. The control group consisted of 30 healthy donors. The antiplatelet therapy was stopped for at least 5 days before CABG. In the postoperative period, from the first day, all patients were received 100 mg of an enteric form of acetylsalicylic acid (ASA). Resistance to ASA was determined at the level of platelet aggregation with arachidonic acid ≥20% by optical agregometry at least at one observation point: before CABG, on 1-3 day and on 8-10 day after surgery. We evaluated the spontaneous and induced lucigenin-dependent chemiluminescence (CL) of platelets (ADP induction) and neutrophils (zymosan induction) by the exit time to maximum intensity (Tmax), maximum intensity (Imax) and area (S) under the CL curve.Results. 70.5% sensitive (sASA) and 29.5% resistant (rASA) to ASA patients were revealed. Prior to CABG, in sASA patients, the Imax of spontaneous and zymosan-induced neutrophil CL and CL platelet activity was increased relative to control values. Tmax of spontaneous platelet CL, Imax and S under the ADP-induced platelet CL curve were lower in sASA patients, if to compare with rASA patients. On the 1st and 8-10th day after CABG in sASA patients, the CL indicators of neutrophil and platelet activity also remained elevated compared to control values. On the 1st day after CABG decreased levels of S under the spontaneous CL curve of neutrophils in rASA patients was established compared with sASA patients, and increased levels of Imax and S under the curve of induced neutrophil CL were detected in comparison with the control range. In rASA patients, the values of Tmax of spontaneous platelet CL decreased in relation to the values detected in the control group and sASA patients. On the 8–10th day after CABG, most indicators of spontaneous and zymosan-induced CL neutrophils in rASA patients were also increased compared to control values. In rASA patients a positive correlation of Imax-induced CL was found (r=0.83) on the 1st day after CABG and negative correlations of Tmax of spontaneous CL (r=- 0.75) and S under the curve induced CL (r=-0.70) on the 8-10th day were detected between platelets and neutrophils.Conclusion. In sASA patients with coronary heart disease before and after CABG, a high level of synthesis of superoxide radical by neutrophils and platelets was detected. The relationship between the levels of the synthesis of superoxide radical by neutrophils and platelets was found only after CABG in rASA patients. Increased synthesis of superoxide radical due to metabolic and regulatory relationships in neutrophils and platelets stimulates pro-inflammatory processes in coronary artery disease and determines the sensitivity of platelets to ASA.

The impacts of C1q/TNF-related protein-15 and adiponectin on Interleukin-6 and tumor necrosis factor-α in primary macrophages of patients with coronary artery diseases

Atherosclerosis is a progressive inflammatory disease characterized by the accumulation of lipids in the arterial wall. Inflammation plays a key role in the pathogenesis of atherosclerosis and some previous studies have shown the role of adipokines during the inflammatory process of atherosclerosis. Therefore, the present study aimed to evaluate the impacts of adiponectin and CTRP15 on inflammatory cytokines secretions from THP1 and primary macrophages. MethodsTHP1 monocytes were differentiated to macrophages and primary monocytes were then isolated from patients with coronary artery disease and controls who were differentiated to macrophages. Macrophages were treated with LPS, LPS+adiponectin, and LPS+CTRP15. ResultsAdiponectin and CTRP15 have reduced IL-6 and TNF-α secretions from LPS-induced THP1 macrophages, and the CTRP15 indicated a more potent anti-inflammatory property compared to adiponectin. In addition, adiponectin reduced cytokines’ expressions and secretions in primary macrophages of both patient and control groups. However, CTRP15 has only reduced cytokines’ expressions and secretions in controls and it was not able to ameliorate inflammation in macrophages of CAD patients. ConclusionThe results of the present study indicate anti-inflammatory impact of adiponectin and CTRP15, while this property was stronger for CTRP15. In addition, it seems likely that anti-inflammatory CTRP15′s impact on macrophages in the CAD patients was weaker than macrophages from the controls.

Dietary habits of patients with coronary artery disease in a tertiary-care hospital of Bangladesh: a case-controlled study

Background and objectivesGlobally, coronary artery disease (CAD) remains one of the leading causes of death, both in developed and less economically developed countries (LEDC) including Bangladesh. Diet plays a key role in the pathogenesis processes of atherosclerosis and coronary artery disease (CAD). The purpose of this study was to assess the dietary habit of heart disease cases that had CAD against matched controls.MethodologyComplying Helsinki ethical norms, with written consent, this case-control study was performed among 210 subjects: 105 CAD-hospitalized patients (selected from Lab Aid Cardiac and Specialized Hospitals) and 105 healthy subjects from local urban communities having their body mass index (BMI: ranging between ≥18.5 and 27 socio-demographic status, detailed-dietary patterns and blood pressure levels were recorded, anthropometric indices measured, and serum biochemistry (complete lipid profile) tested/analyzed for both the cases and controls. All visually re-checked data were analyzed using appropriate statistical tools (t test/conditional-logistic regressions) on SPS/Windows V.21.0.ResultAlmost half (45%) CAD patients had hypertriglyceridemia and higher levels of low-density lipoprotein, significantly higher BMA (p=0.001), waist circumference, and waist to hip ratio in male patients (p=0.005 and p=0.020, respectively) than their peer controls. Serum lipid profiles, sugar concentrations, and blood pressure levels of CAD patients revealed higher levels than clinically defined cut-off values as established risk factors for CAD. Odds ratios (CI 95%) as risk factors for consuming junk food {OR=5.49 (2.25–13.38)}, chicken {OR=4.54 (1.89–10.9) was the most, followed by beef {OR=2.68 (1.19–4.98)}, eggs {OR=2.38 (1.14–10.92)}, fish {OR=2.81 (1.31–6.04)}, and vegetables {0R=.968 (0.510–1.839)}. However, fat-free milk, ghee/butter oil, curd/yogurt, and fruits had lower ORs revealing no or less risks for CAD.ConclusionFood habits of CAD patients (with higher BMI level and biochemical indicators of the blood) statistically revealed that consuming junk food, meat, and eggs being riskier, fruits, fat-free milk, yogurt, and vegetable remains have protective effects on CAD.

Circular RNA PPP1CC promotes Porphyromonas gingivalis-lipopolysaccharide-induced pyroptosis of vascular smooth muscle cells by activating the HMGB1/TLR9/AIM2 pathway.

ObjectivePorphyromonas gingivalis (Pg) plays a critical role in the occurrence and development of atherosclerosis. Lipopolysaccharide from Pg (Pg-LPS) could lead to pyroptosis of vascular smooth muscle cells (VSMCs) and induce instability of atherosclerotic plaque. Therefore, pyroptosis of VSMCs could promote the process of atherosclerosis. However, the exact mechanism of Pg-LPS-induced pyroptosis of VSMCs is unclear.MethodsWe determined pyroptosis and expression of interleukin (IL)-1β and IL-18 in VSMCs using 4′,6-diamidino-2-phenylindole staining and ELISA after stimulation by Pg-LPS. We established a knockdown plasmid containing the circular (circ)RNA PPP1CC and transfected it into VSMCs. Luciferase assays were performed to reveal the association between microRNAs miR-103a-3p and miR-107 and circRNA PPP1CC.ResultsStimulation of Pg-LPS led to pyroptosis of VSMCs. Knockdown of circRNA PPP1CC relieved the Pg-LPS-induced pyroptosis of VSMCs and suppressed the expression of HMGB1, TLR9, AIM2, and cleaved caspase-1. Luciferase assays showed that PPP1CC directly targeted and competitively adsorbed miR-103a-3p and miR-107, weakening the inhibitory effect of these microRNAs on the expression of HMGB1.ConclusionKnockdown of circRNA PPP1CC relieved Pg-LPS-induced pyroptosis of VSMCs. Pyroptosis of VSMCs appears to promote atherosclerosis and may represent a novel therapeutic target for its treatment.

Pediatric Lipid Disorders.

Current scientific evidence has proven that atherosclerosis is a process that begins in childhood and tracks into adulthood, likely culminating in adverse cardiovascular events such as coronary artery disease, peripheral artery disease, and stroke. In addition, the obesity epidemic and increasing awareness of genetic lipid disorders has made the understanding and management of lipid disorders necessary for pediatricians. Childhood offers a unique opportunity for preventing, modifying, or eliminating risk factors and, in doing so, reversing or slowing the process of atherosclerosis. In general, management involves targeted lifestyle interventions such as strict dietary changes and increases in physical activity. In some circumstances, pharmacotherapy, even in childhood, is warranted. [Pediatr Ann. 2021;50(3):e105-e112.].