Major Risk Factor For Atherosclerosis Research Articles

Targeting vascular senescence in cardiovascular disease with aging

Aging is a major risk factor for atherosclerosis and cardiovascular disease (CVD). Two major age-associated arterial phenotypes, endothelial dysfunction and large elastic arterial stiffness, are autonomous predictors of future CVD diagnosis and contribute to the progression of CVD in older adults. Senescent cells lose the capacity to proliferate but remain metabolically active and secrete inflammatory factors termed senescence-associated secretory phenotype (SASP), leading to an increase in inflammation and oxidative stress. Accumulation of senescent cells is linked with the progression of age-related diseases and has been known to play a role in cardiovascular disease. In this brief review, we describe the characteristics and mechanisms of senescent cell accumulation and how senescent cells promote endothelial dysfunction and arterial stiffness. We focus on a range of novel therapeutic strategies aimed at reducing the burden of endothelial dysfunction leading to atherosclerosis through targeting senescent cells. Studies have begun to investigate a specific class of drugs that are able to selectively eliminate senescent cells, termed senolytics, which have shown great promise in reversing the aging phenotype and ameliorating pathologies in age-related disorders, creating a new opportunity for aging research. Generating therapies targeting the elimination of senescent cells would improve health span and increase longevity, making senolytics a promising therapy for cardiovascular diseases.

Study of active components and mechanisms mediating the hypolipidemic effect of Inonotus obliquus polysaccharides.

Hyperlipidemia is a multifaceted metabolic disease, which is the major risk factor for atherosclerosis and cardiovascular diseases. Traditional Chinese medicine provides valuable therapeutic strategies in the treatment of hyperlipidemia. Inonotus obliquus has been used in traditional medicine to treat numerous diseases for a long time. To screen and isolate the fractions of I. obliquus polysaccharides (IOP) that can reduce blood lipid in the hyperlipemia animals and cell models, and investigate its mechanisms. The active component IOP-A2 was isolated, purified, and identified. Invivo, rats were randomly divided into blank control group (NG), the high-fat treatment group (MG), lovastatin group (PG), and IOP-A group. Compared with MG, the hyperlipidemic rats treated with IOP-A2 had decreased body weight and organ indexes, with the level of serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) significantly decreased (p < .05), and level of serum high-density lipoprotein cholesterol (HDL-C) significantly increased (p < .05). Hepatocyte steatosis in hepatic lobules was significantly reduced. Invitro, the accumulation of lipid droplets in the model of fatty degeneration of HepG2 cells was significantly alleviated, and cellular TC and TG content was significantly decreased (p < .01). Moreover, the expression of recombinant cytochrome P450 7A1 (CYP7A1) and Liver X Receptor α (LXRα) were up-regulated (p < .05) both invivo and invitro. The results showed that IOP-A2 may exert its hypolipidemic activity by promoting cholesterol metabolism and regulating the expression of the cholesterol metabolism-related proteins CYP7A1, LXRα, SR-B1, and ABCA1.

Evaluation of the Influence of oral administration of Aqueous Leaf Extract of Sida acuta on Lipid Profile and Body Weight of Wistar Rats

Abnormalities in serum lipid profiles play a central role in endothelial functional abnormality which is a major risk factor for atherosclerosis including coronary artery disease, cerebrovascular disease and peripheral vascular diseases. Hepatic damage disturbs hepatic functions such as lipid metabolism which can translate to a distorted lipid profile. Therefore, the aim of this study was to evaluate the influence of oral administration of Sida acuta on the lipid profile and body weight of Wistar rats. Freshly harvested leaves of Sida acuta was dried under room temperature and afterwards ground to powder which was subsequently processed into extract. Thirty adults male Wistar rats were divided into five groups of five rats each. Group I (normal control) was administered with 2 ml of distilled water, groups II–VI were induced hepatic damage. While group II was left untreated, groups III-V were administered with 100, 200 and 300 mg/kg of aqueous extract of Sida acuta (AESD) respectively. Group VI was administered with silymarin (standard drug). Treatment lasted for 28 days after which animals were humanely sacrificed and blood sample collected for analysis. Treatment with extract significantly (P&lt;0.05) reduced the activities of the liver enzymes; aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP). While the serum levels of TC, TG, HDL and LDL reported for group II were significantly (P&lt;0.05) higher than those reported for the normal control. Oral administration of extract significantly (p&lt;0.05) reduced the levels of TC, TG, HDL and LDL reported for groups III-V. Oral administration of extract did not adversely affect the body weight of animals. In conclusion, it can be deduced from this study that oral administration of Sida acuta reversed a distorted lipid profile and did not result in weight loss.

Cells in Atherosclerosis: Focus on Cellular Senescence from Basic Science to Clinical Practice.

Aging is a major risk factor of atherosclerosis through different complex pathways including replicative cellular senescence and age-related clonal hematopoiesis. In addition to aging, extracellular stress factors, such as mechanical and oxidative stress, can induce cellular senescence, defined as premature cellular senescence. Senescent cells can accumulate within atherosclerotic plaques over time and contribute to plaque instability. This review summarizes the role of cellular senescence in the complex pathophysiology of atherosclerosis and highlights the most important senotherapeutics tested in cardiovascular studies targeting senescence. Continued bench-to-bedside research in cellular senescence might allow the future implementation of new effective anti-atherosclerotic preventive and treatment strategies in clinical practice.

Lipid Profile in Olympic Athletes: Proposal for a “Lipid Athlete Score” as a Clinical Tool to Identify High-Risk Athletes

Dyslipidemia is a major risk factor for atherosclerosis. Identification of dyslipidemia in athletes has raised interest in establishing preventive strategies and reducing cardiovascular (CV) events. Nowadays, targets or “scores” for athletes are undefined. The aim of our study was to create a “Lipid Athlete Score” based on lipid parameters and derive score indexes to identify high-risk athletes. We retrospectively enrolled 957 Olympic athletes practicing different sporting disciplines (power, skills, endurance, and mixed), analyzing their CV profiles and anthropometrics; 55.4% were male, the mean age was 27.1 ± 5 years, and the mean body mass index (BMI) was 23.1 ± 3.2 kg/m2. Three hundred and forty-three athletes (35.8%) were dyslipidemic (LDL ≥ 115 mg/dL or LDL/HDL ≥ 1.90). Multivariate analysis revealed the following: male p = 0.001, OR 1.88 [0.41–2.51], familiarity for dyslipidemia p = 0.001, OR 2.82 [1.72–4.59], BMI ≥ 30 kg/m2 p = 0.001, OR 2.53 [1.46–4.38], and fat mass p = 0.001, OR 2.29 [1.38–3.80] were significant. Endurance athletes presented the lowest CV risk. We proposed a lipid athlete score including major (LDL ≥ 115 mg/dL and LDL/HDL ≥ 1.90) and minor criteria (male, BMI &gt; 30 kg/m2 or fat mass &gt;22% for males and 32% for females, familiarity for dyslipidemia, and conventional CV risk factors). Twelve athletes (1.2%) were at high risk, 150 athletes (15.7%) at medium risk, 171 athletes (17.9%) at low risk, and 624 (65.2%) were at no risk. Dyslipidemia is very common in elite athletes. We have defined a specific lipid athlete score based on lipid parameters and derived score indexes for the stratification of risk. In accordance with this tool, a substantial proportion of athletes (16.9%) were at medium-to-high risk and need early preventive strategies to improve their lipid profiles and reduce the future development of atherosclerotic CV diseases.

Helicobacter pylori (H. pylori) Infection-Associated Dyslipidemia in the Asir Region of Saudi Arabia.

H. pylori-associated dyslipidemia has been reported to be a major risk factor for atherosclerosis and coronary heart diseases. We aimed to investigate the association of the H. pylori infection with dyslipidemia. A retrospective case-control study was undertaken to evaluate H. pylori-associated dyslipidemia, where H. pylori-positive individuals were treated as the case group (n = 260) while H. pylori-negative individuals were considered as the control group (n = 250). The mean ± SD of the age of the patients included (n = 510) was 44.01 ± 13.58 years. Study subjects with a total cholesterol level of >5.17 mmol/L and/or a triglyceride level of >1.69 mmol/L and/or an LDL-C level of >2.59 mmol/L and/or an HDL-C level of <1 mmol/L in males and/or an HDL-C level of <1.3 mmol/L in females were defined as dyslipidemia. Descriptive (mean, standard deviation, median, and IQR) and inferential (t-test, chi-square test, and logistic regression) statistical analyses were undertaken using the R-base/R-studio (v-4.0.2)/tidyverse package. Univariate and bivariate logistic regressions were executed to calculate the crude and adjusted odds ratio along with the p-value. A p-value of <0.05 was the cut-off for statistical significance. We used ggplot2 for data visualization. The differences in overall mean ± SD (H. pylori positive vs. negative) of the cholesterol (5.22 ± 1.0 vs. 5.49 ± 0.85, p < 0.01), triglyceride (1.66 ± 0.75 vs. 1.29 ± 0.71, p < 0.001), LDL-C (3.43 ± 0.74 vs. 3.26 ± 0.81, p < 0.05), and HDL-C (1.15 ± 0.30 vs. 1.30 ± 0.25, p < 0.001) levels were statistically significant. The cholesterol and LDL-C levels in ages >60, age = 30-60, in females, and LDL-C levels in males were not significantly different for the H. pylori-positive and -negative groups. The proportion (H. pylori positive vs. negative) of hypercholesterolemia (190/59.9% vs. 127/40% p < 0.01), hypertriglyceridemia (136/68% vs. 64/32% p < 0.001), high LDL-cholesterolemia levels (234/53% vs. 201/46% p < 0.01), and low HDL-cholesterolemia levels (149/71% vs. 60/28.7% p < 0.01) were statistically significant. The odds of having hypercholesterolemia (AOR: 2.64, 95%CI: 1.824-3.848, p < 0.001), hypertriglyceridemia (AOR: 3.24, 95%CI: 2.227-4.757, p < 0.001), an increased LDL-C level (AOR: 2.174, 95%CI: 1.309-3.684, p < 0.01), and a decreased HDL-C level (AOR: 4.2, 95%CI: 2.937-6.321, p < 0.001) were 2.64, 3.24, 2.17, and 4.2 times higher in the H. pylori-infected individuals as compared with the H. pylori-uninfected group. Our results demonstrate that an enhanced risk of dyslipidemia is associated with the H. pylori infection, which can aggrandize the atherosclerosis process. The evaluation of temporal variation in the lipid profile in H. pylori-infected individuals is recommended for the effective management of H. pylori-infected patients.

Signal Pathways and Intestinal Flora through Trimethylamine N-oxide in Alzheimer's Disease.

The current studies show signs of progress in treating Alzheimer's disease (AD) with the "brain-gut axis." Restoring intestinal flora balance can alleviate neurodegeneration in the central nervous system. However, due to the complex mechanisms involved in the brain-gut axis, the neuroprotective mechanism brought by intestinal flora has not been fully understood. Trimethylamine N-oxide (TMAO) is a microbiota-dependent metabolism production; TMAO has been proven to be a major risk factor for atherosclerosis, thrombosis, type II diabetes, and other diseases. Meanwhile, all the above diseases are associated with AD; thus, we speculate that TMAO and AD are also correlated. Microbiota, such as Firmicutes, Ruminococcaceae, Escherichia coli, Bifidobacterium, Akkermansia, etc., correlate with the production process of TMAO. High choline intake and insulin resistance have also been identified as contributors to TMAO synthesis. With the increasing TMAO in plasma, TMAO can enter the central nervous system, causing neuroinflammation and immune responses and damaging the blood-brain barrier. TMAO can increase the expression of Aβ and the hyperphosphorylation of tau protein, regulate the signal pathways of NLRP3/ASC/caspase1, SIRT1/p53/p21/Rb, PERK/eIF2α/ER-stress, SIRT3-SOD2-mtROS, TXNIP-NLPR3, and PERK/Akt/mTOR, and stimulate the inflammation, apoptosis, endoplasmic reticulum stress, and the ROS. In this mini-review, we have summarized the diseases induced by TMAO through clinical and signal pathways, and intestinal flora correlated with TMAO. Through the analysis of diseases and mechanisms involved in TMAO, we have concluded TMAO to be a potentially important pathological factor of AD.

Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review.

Hyperlipidemia is a metabolic disorder, which is a major risk factor for atherosclerosis, stroke, and coronary heart disease. Although lipid-lowering treatments have been extensively studied, safer treatments with fewer adverse effects are needed. Rhubarb is a traditional Chinese medicine that has lipid-lowering, anti-inflammatory, and antioxidant properties. Disturbance in lipid metabolism is the basis of tissue damage caused by hyperlipidemia and plays a key role in the development of hyperlipidemia; however, the molecular mechanisms by which rhubarb regulates lipid metabolism to lower lipid levels are yet to be elucidated. We conducted this study to summarize the phytochemical constituents of Rheum officinale and provide a comprehensive review of the molecular mechanisms underlying the regulation of lipid metabolism during hyperlipidemia treatment. It was found that rhubarb extracts, including emodin, rhubarb acid, and rhubarb phenol, regulate total cholesterol, triglyceride, TNF-α, and IL-1β levels through signaling pathways such as C/EBP α, 3T3-L1, PPAR α, and AMPK, thereby improving the hyperlipidemic state. This suggests that rhubarb is a natural drug with lipid-lowering potential, and an in-depth exploration of its lipid-lowering mechanism can provide new ideas for the prevention and treatment of hyperlipidemia.

Design, optimization, and in vivo evaluation of invasome-mediated candesartan for the control of diabetes-associated atherosclerosis

Atherosclerosis is an inflammatory disease characterized by the accumulation of arterial plaque. Diabetes mellitus stands out as a major risk factor for atherosclerosis. Candesartan is a potent angiotensin II receptor antagonist that enhances arterial blood flow and reduces insulin resistance. However, oral candesartan has limited activity because of its low bioavailability, water solubility, hepatic first-pass degradation, and efficacy. The current study aims to develop nasal candesartan-loaded invasome (CLI) drops to improve candesartan’s permeation, release, and bioavailability as a potential treatment for diabetes-associated atherosclerosis. Design expert software was used to prepare various CLI formulations to determine the impact of the concentrations of ethanol, cineole, and phospholipid. The desirability index was used to estimate the optimized formulation composition to maximize entrapment efficiency and minimize vesicle size. The optimized formulation had a 1% ethanol concentration, a 1.5% cineole concentration, and a 2.32% phospholipid concentration. The selected optimized formulation was then tested in a rat model of diabetes and atherosclerosis to evaluate its activity. The results showed that nasal CLI drops significantly raised serum HDL levels by a ratio of 1.42 and lowered serum glucose, cholesterol, triglycerides, LDL, and VLDL levels by 69.70%, 72.22%, 36.52%, 58.0%, and 65.31%, respectively, compared with diabetic atherosclerotic rats, throwing an insight on the potential for promising anti-diabetic and anti-atherosclerotic activities. Additionally, atherosclerotic lesions were improved in rats treated with CLI, as shown in histopathology. In conclusion, the results of this investigation showed that treatment with nasal CSN-loaded invasome formulation drops prevented the initiation and progression of diabetes-associated atherosclerosis.Graphical

Abstract P3033: Thrombospondin-1 Promotes Vascular Smooth Muscle Cell De-differentiation In Diabetes

Diabetes is a major risk factor for atherosclerosis. Diabetic patients are prone to increased vascular smooth muscle cell (VSMC) migration and proliferation, hallmarks of VSMC de-differentiation, critical for the evolution of atherosclerosis. Multiple studies, including our earlier work, support the role of thrombospondin-1 (TSP1), a proatherogenic matricellular protein, as a putative link between diabetes and vascular disease. However, molecular mechanism(s) by which TSP1 promotes diabetic vasculopathy are incompletely understood. The goal of this work was to explore whether smooth muscle TSP1 (smTSP1) regulates VSMC phenotypic switch in diabetes. We generated conditional SMC-specific TSP1 knockout (smTSP1 KO ) mice by crossing female TSP1 fl/fl mice with tamoxifen (tmx)-inducible Myh11-CreER T2 male mice. For Cre recombination, 5-wks-old male TSP1 fl/fl Cre tg and age-matched TSP1 +/+ Cre tg littermate mice were treated with 60 mg/Kg/day tmx i.p. once daily for 5 consecutive days. To induce type 2 diabetes, mice cohorts were placed on western diet at 7-wks-age followed by streptozotocin (50 mg/Kg/day, i.p. x 5 days) at 16-wks-age. Mice were harvested at 20-wks-age for plasma and tissue collection. Immunoblotting of aortic lysates revealed significant decrease in TSP1 expression in tmx-treated TSP1 fl/fl Cre tg , validating smTSP1 KO mice. Lack of smTSP1 increased ACTA2 (SM contractile marker) expression by 2-fold accompanied with 50% reduction in CDK4 (cell cycle regulator) expression in diabetic smTSP1 KO vs. smTSP1 WT aortic vessels. Consistently, in murine aortic SMC (MASMC) primary cultures derived from smTSP1 KO mice, loss of smTSP1 augmented (&gt;65%) LMOD1 (SM contractile marker) and SRF (transcriptional activator of SM contractile genes) expression coupled with diminished (45%) vimentin (SM synthetic marker) expression in 25mM glucose-treated smTSP1 KO vs. smTSP1 WT cells. Further, propidium iodide staining via flow cytometry revealed reduced S-phase cell counts concomitant to increased G 0 -G 1 cell distribution in glucose-treated smTSP1 KO vs. smTSP1 WT MASMC. Together, our data demonstrates a direct role of TSP1 in VSMC phenotypic transition and opens novel avenues for cell-specific TSP1-based therapies for treatment of diabetes.

Prognostic value of hematological parameters in older adult patients with acute coronary syndrome undergoing coronary intervention: a single centre prospective study.

Cardiovascular disease is a significant contributor to the disease burden in geriatric patients. Underlying systemic inflammation is thought to be the cause of age-related changes in the bone marrow and a major risk factor for atherosclerosis. The purpose of the study was to assess the accuracy of these hematological biomarkers in predicting 30-day mortality in older patients with acute coronary syndrome (ACS). This was a prospective observational study of 601 older adult patients (age > 60 years) with ACS who underwent percutaneous coronary intervention over two years (2017-2019). The relationship between baseline hematological parameters and mortality was assessed during the 30-day follow-up. Logistic regression analysis and receiver operating characteristic curve analysis were done to evaluate for diagnostic accuracy of various hematological parameters. The mean age of presentation was 77 ± 17 years. The mean neutrophil-lymphocyte ratio (NLR) value was 5.07 ± 4.90 and the mean platelet-lymphocyte ratio (PLR) value was 108.65 ± 85.82. On univariate analysis, total leucocyte count [odds ratio (OR) = 0.85, P = 0.021], hematocrit (OR = 0.91, P = 0.018), NLR (OR = 1.10, P = 0.001) and PLR (OR = 1.05, P = 0.001) were associated with mortality. On receiver operating characteristic curve analysis, NLR predicted mortality with 68.1% and PLR with 65.7% accuracy. On multivariate analysis, NLR (OR = 1.096, 95% CI: 1.006-1.15, P = 0.035) was an independent predictor of 30-day mortality. For the risk classification of all elderly ACS patients, we highly advise using NLR rather than the total white blood cell count.

The cardioprotective effects of secoisolariciresinol diglucoside (flaxseed lignan) against cafeteria diet-induced cardiac fibrosis and vascular injury in rats: an insight into apelin/AMPK/FOXO3a signaling pathways.

Introduction: Fast food is a major risk factor for atherosclerosis, a leading cause of morbidity and mortality in the Western world. Apelin, the endogenous adipokine, can protect against cardiovascular disease via activating its receptor, APJ. Concurrently, secoisolariciresinol diglucoside (SDG), a flaxseed lignan extract (FLE), showed a therapeutic impact on atherosclerosis. The current study aimed to examine the effect of SDG on cafeteria diet (CAFD)-induced vascular injury and cardiac fibrosis via tracking the involvement of the apelin/APJ pathway. Methods: Thirty male rats were allocated into control, FLE-, CAFD-, CAFD/FLE-, and CAFD/FLE/F13A-treated rats, where F13A is an APJ blocker. All treatments lasted for 12weeks. Results and discussion: The CAFD-induced cardiovascular injury was evidenced by histological distortions, dyslipidemia, elevated atherogenic indices, cardiac troponin I, collagen percentage, glycogen content, and apoptotic markers. CAFD increased both the gene and protein expression levels of cardiac APJ, apelin, and FOXO3a, in addition to increasing endothelin-1, VCAM1, and plasminogen activator inhibitor-1 serum levels and upregulating cardiac MMP-9 gene expression. Moreover, CAFD reduced serum paraoxonase 1 and nitric oxide levels, cardiac AMPK, and nuclear Nrf2 expression. FLE attenuated CAFD-induced cardiovascular injury. Such effect was reduced in rats receiving the APJ blocker, implicating the involvement of apelin/APJ in FLE protective mechanisms. Conclusion: FLE supplementation abrogated CAFD-induced cardiac injury and endothelial dysfunction in an apelin/APJ-dependent manner.

463-P: Risk Stratification of Coronary Artery Disease (CAD) according to LDL-C, HDL-C Levels, and Glucose Status

Whereas elevated LDL-C is a major risk factor for CAD, the inverse association between HDL-C levels and risk of CAD is well-known. Although insulin resistance, and glucose intolerance are associated with low HDL-C levels, it is not clear whether the association of LDL-C with CAD differs depending on glucose status and HDL-C values. We examined associations of LDL-C with the incidence of CAD according to HDL-C and glucose status using a nationwide claims database on 1,524,289 individuals during 2008-2019 with no history of CAD or familial hypercholesterolemia. Cox proportional hazards model identified risks of CAD events among combinations of 3 levels of HDL-C and 7 levels of LDL-C according to glucose status. During a mean follow-up period of 5.5 years, 8,301 CAD events occurred. CAD risk increased from lower LDL-C levels accompanied by lower HDL-C levels regardless of glucose status (Table). Even in people with LDL-C &amp;lt;80mg/dl, HDL-C &amp;lt;40mg/dl conferred 2.5-fold increased risk of CAD all glucose status. HDL-C and LDL-C values had a synergistic effect on the incidence of CAD in people with normoglycemia, whereas an addictive effect in people with prediabetes and diabetes. Although more strict LDL-C target need to be achieved as worsening of glucose status, results demonstrated that the necessity of modulating the LDL-C target according to HDL-C levels is not affected by glucose status. Disclosure M.H.Yamada: None. M.Iwanaga: None. T.Yamada: None. S.Kodama: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. K.Fujihara: None. T.Osawa: None. M.Kitazawa: None. Y.Yaguchi: None. T.Sato: None. Y.Mitsuma: None. M.Yamamoto: None. Y.Matsubayashi: None.

Relation between aortic elasticity parameters and SYNTAX score in postmenopausal diabetic women

BackgroundPostmenopausal women are at increased risk of coronary artery disease (CAD). Diabetes Mellitus is a major risk factor for CAD. The stiffening of the aorta is associated with increased cardiovascular morbidity and mortality. We aimed to investigate the relation of aortic elasticity parameters to CAD severity assessed by SYNTAX score (SS) in diabetic postmenopausal women. The study prospectively included 200 consecutive diabetic postmenopausal women with CAD who underwent elective coronary angiography. Patients were classified into 3 groups based on SS, low-SS ≤ 22, intermediate-SS ≥ 23– ≤ 32, and high-SS ≥ 33. Echocardiographic aortic elasticity parameters, including aortic stiffness index (ASI), aortic strain (AS) (%) and aortic distensibility (AD) were obtained in all patients.ResultsPatients in the high SS group were older age and had a higher aortic stiffness. After adjusting different co-variates AD, AS, and ASI could be used as independent predictors of high SS with the following P-values (0.019, 0.016 and 0.010) and cut-off values (2.5, 3.6 and 2.9), respectively.ConclusionsIn diabetic postmenopausal women, the simple echocardiography-derived aortic elasticity parameters might predict the severity and complexity of angiographic coronary lesions assessed by the SS.

Hyperhomocysteinemia, Hyperlipidemia and Retina

Hyperhomocysteinemia is a disease with an increase in the plasma level of homocysteine, an intermediate of methionine metabolism, and predisposes to thrombosis. It is a well-established risk factor for occlusive cardiovascular illnesses and has been linked to ocular pathologies such as retinal vascular disorders, age-related macular degeneration, and most notably ectopia lentis. Lipids compose approximately 20% of the dry weight of the retina. Apart from their structural significance, lipids also serve a critical function in providing the necessary energy for the metabolic needs of the retina. Hyperlipidemia is described as an abnormally high level of blood cholesterol and triglycerides and is a major risk factor for atherosclerosis. It may increase the risk of retinal vascular disorders secondary to atherosclerosis-like processes in the retina. Through the inflammatory process they generate, hyperhomocysteinemia and hyperlipidemia may also contribute to the progression of retinal vascular disorders such as diabetic and hypertensive retinopathy and retinopathy of prematurity.

Diagnostics, monitoring and treatment of arterial hypertension in children

The review presents material on the current relevance of AH in children. The prevalence of AH in overweight and obese children aged 6-18 years is 27–47 %, while secondary arterial hypertension remains dominant, especially in children younger than 5 years. AH is a major risk factor for atherosclerosis and cardiovascular disease in adults. The onset of these diseases may occur in childhood or adolescence. The use of modern methods to monitor and control BP is crucial for improving the management of AH and preventing damage to target organs. Twenty-four-hour BP measurements are an important tool in determining the prognosis and treatment of children with AH. AH in children can be classified as primary or essential if there is no identifiable cause, or as secondary AH when it arises from a specific cause. The incidence of primary arterial hypertension increases with age, whereas secondary arterial hypertension predominates in early childhood. The secondary causes of AH also depend on the age of the patient. Thus 34-79 % of patients with secondary forms of arterial hypertension have renal parenchymal disease and impaired renal structure. Signs of AH include headache, visual disturbances, dizziness and nosebleeds. Dyspnoea on exercise, facial paralysis and seizures indicate target organ damage. In children with obesity, diabetes, renal insufficiency, aortic coarctation/repaired coarctation and those receiving medication causing AH, BP should be measured at every visit to the physician. Therapeutic lifestyle changes are an early therapy in the treatment of AH in children. IAPs, BCAAs, BRAs and thiazide diuretics are the most effective drugs for AH in children.

Cigarette smoke induces mitochondrial DNA damage and activates cGAS-STING pathway -Application to a biomarker for atherosclerosis.

Cigarette smoking is a major risk factor for atherosclerosis. We previously reported that DNA damage was accumulated in atherosclerotic plaque, and was increased in human mononuclear cells by smoking. As vascular endothelial cells are known to modulate inflammation, we investigated the mechanism by which smoking activates innate immunity in endothelial cells focusing on DNA damage. Further, we sought to characterize the plasma level of cell-free DNA (cfDNA), a result of mitochondrial and/or genomic DNA damage, as a biomarker for atherosclerosis. Cigarette smoke extract (CSE) increased DNA damage in the nucleus and mitochondria in human endothelial cells. Mitochondrial damage induced minority mitochondrial outer membrane permeabilization, which was insufficient for cell death but instead led to nuclear DNA damage. DNA fragments, derived from the nucleus and mitochondria, were accumulated in the cytosol, and caused a persistent increase in IL-6 mRNA expression via the cGAS-STING pathway. cfDNA, quantified with quantitative PCR in culture medium was increased by CSE. Consistent with in vitro results, plasma mitochondrial cfDNA (mt-cfDNA) and nuclear cfDNA (n-cfDNA) were increased in young healthy smokers compared to age-matched non-smokers. Additionally, both mt-cfDNA and n-cfDNA were significantly increased in patients with atherosclerosis compared to the normal controls. Our multivariate analysis revealed that only mt-cfDNA predicted the risk of atherosclerosis. In conclusion, accumulated cytosolic DNA caused by cigarette smoke and the resultant activation of the cGAS-STING pathway may be a mechanism of atherosclerosis development. The plasma level of mt-cfDNA, possibly as a result of DNA damage, may be a useful biomarker for atherosclerosis.

Evaluation of Serum Cysteine-rich Angiogenic Inducer 61 for Peripheral Arterial Disease in Patients with Type 2 Diabetes Mellitus

Abstract Background: Peripheral artery disease (PAD) is a common manifestation of atherosclerotic disease, which is related to considerable disability and mortality. Currently, approximately 202 million people worldwide are suffering from lower extremity arterial disease, giving rise to a major public health problem and a heavy economic burden. Type 2 diabetes mellitus (T2DM) is one of the major risk factors for atherosclerosis, and the prevalence of PAD increases with the prevalence of T2DM. Materials and Methods: A cross-sectional case–control study comprising 100 cases and 40 age- and sex-matched healthy controls was done. The cases were divided into three groups: Group 1 (T2DM with PAD) – 40, Group 2 (T2DM without PAD) – 40, and Group 3 (PAD without T2DM) – 20. The serum cysteine-rich angiogenic inducer 61 (CYR61) levels were assessed using the sandwich enzyme-linked immunosorbent assay. Statistical analysis was done using MedCalc version 20.114. P &lt;0.005 is taken as statistically significant. Results: The mean concentrations of CYR61 in Group 1, Group 2, and Group 3 were 3680 pg/ml, 3059 pg/ml, and 2866 pg/ml, respectively, whereas, in controls, it was 2318 pg/ml. The serum CYR61 levels were significantly higher in cases compared to controls (P &lt; 0.0001). CYR61 concentrations are significantly higher in Group 1 compared to the other two groups – Group 2 and Group 3. CYR61 levels showed a statistically significant difference between Stage 2 and Stage 4 of PAD in Group 1. Receiver operating characteristic analysis has shown area under curve (0.946) for CYR61 higher than ankle-brachial index (0.750). Conclusions: CYR61 proved to be a better marker for diagnosing PAD in patients with T2DM.

ABO Blood Group and Severity of Coronary Artery Disease Assessed by Syntax Score in Patients with Acute Myocardial

Introduction: As coronary artery disease (CAD) is a major cause of morbidity and mortality; timely diagnosis and appropriate therapy is of paramount importance to improve clinical outcomes. Though there are major risk factors for CAD but sometimes it does not correlate with ACS. So, search for new risk factor is necessary for better management of CAD specially STEMI. Aim: To see the association between ABO blood group and severity of CAD in patients with STEMI. Methods: This study was done during the period of January 2016 to June 2016 with STEMI at National Institute of Cardiovascular diseases, Dhaka, Bangladesh. 100 patients were grouped in I and II where group-I having 50 patients of non-O blood group and group-II having 50 patients of O blood group. After CAG all reports were analyzed by two experts and SYNTAX score were calculated and data were analyzed by SPSS. Results: Baseline characteristics (100 patients) were well matched between the groups. Low SYNTAX score (d”22) was 16% and 56%; intermediate score (23-32) was 40% and 36% and high score (&gt;32) was 44% and 8% in group- I and group-II respectively. These indicate that patients of non-O blood group have high SYNTAX score that is more severe CAD. Univariate and multivariate regression analysis showed that non-O blood group is an independent risk factor for CAD. So easily available ABO blood grouping can be helpful to determine the severity of CAD in patients with STEMI. Bangladesh Heart Journal 2022; 37(2): 107-115

G0S2 ameliorates oxidized low-density lipoprotein-induced vascular endothelial cell injury by regulating mitochondrial apoptosis.

Oxidative low-density lipoprotein (ox-LDL)-induced endothelial cell damage is a major risk factor for atherosclerosis and its related cardiovascular diseases. The G0/G1 switch gene 2 (G0S2) is a multifunctional protein which has been poorly studied in atherosclerosis. In this study, ox-LDL was utilized to construct a human aortic endothelial cell (HAEC) injury model. It was found that ox-LDL impaired cell viability, augmented lactate dehydrogenase (LDH) release, and reduced G0S2 levels in HAECs in a dose-dependent manner. Further, G0S2 overexpression improved the viability and restrained apoptosis of HAECs treated by ox-LDL. Conversely, G0S2 depletion decreased the viability and aggravated apoptosis of HAECs treated by ox-LDL. At the molecular level, G0S2 overexpression significantly increased the secretion of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPH-Px), promoted intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) content in HAECs under either normal or ox-LDL conditions. Meanwhile, the ox-LDL-induced mitochondrial dysfunction, as demonstrated by decreased mitochondrial membrane potential, translocation of mitochondrial cytochrome c (Cyt-c) to the cytoplasm, and activation of caspase-3 and caspase-9, was significantly reversed by G0S2 overexpression. In addition, G0S2 overexpression promoted the activation of AMP-activated protein kinase (AMPK) and increased the expression of nuclear factor erythroid-2-related factor-2 (Nrf2), sirtuin 1 (SIRT1) and heme oxygenase 1 (HO-1) under normal and ox-LDL conditions. This study demonstrated that G0S2 protects against ox-LDL-induced vascular endothelial cell injury by regulating oxidative damage and mitochondrial homeostasis and may be a promising target for the treatment of atherosclerosis.