Immunoexpression of aortic endothelial P-selectin and serum apolipoprotein A-1 levels after administration of arabica (Coffea arabica) and robusta (Coffea canephora) coffee bean extracts: In vivo study in atherosclerosis rat model.

Atherosclerosis is a leading cause of cardiovascular disease-related death worldwide. Some studies suggested that the natural ingredients in coffee may negatively affect cardiovascular diseases, while other studies indicated that coffee contains anti-inflammatory compounds that are beneficial for cardiovascular diseases. The aim of this study was to measure the expression of P-selectin in aortic endothelial cells and the level of serum apolipoprotein A-1 (ApoA-1) in an atherosclerosis rat model after the administration of arabica and robusta coffee bean extracts at mild-moderate and high doses. An experimental study was conducted with a complete randomized design using 36 adult male white rats (Rattus norvegicus) divided into six groups: negative control (NC), positive control (PC), arabica mild-moderate dose (A1), arabica high dose (A2), robusta mild-moderate dose (R1), and robusta high dose (R2). Animals were induced atherosclerosis with atherogenic feed and then were treated with arabica and robusta coffee bean extracts at two different doses for four weeks. The results showed that the expression of P-selectin in the group of rats treated with robusta coffee bean extract was lower than arabica coffee bean extract group. Rats with robusta coffee bean extract mild-moderate dose had the highest ApoA-1 levels compared to other groups significantly (p<0.05). The level of ApoA-1 was higher in both mild-moderate and high dose of robusta coffee groups compared to the negative control group (both with p<0.001). In conclusion, mild-moderate intake of robusta coffee bean extract could reduce aortic P-selectin immunoexpression and increase serum ApoA-1 levels in an atherosclerosis rat model.

Association between NT-proBNP level and the number of stents with major advanced cardiovascular events (MACE) in patients with multivessel coronary artery disease treated with percutaneous coronary intervention: A prospective cohort study.

Complex revascularization strategies, particularly complete revascularization, are controversial in coronary artery disease (CAD), and data supporting routine revascularization in stable CAD is lacking. The importance of percutaneous coronary intervention (PCI) in CAD and N-terminal pro-brain natriuretic peptide (NT-proBNP), which has been studied as a predictor of major advanced cardiovascular events (MACE) in CAD patients, still requires further research. The aim of this study was to determine the association between NT-proBNP levels and the number of stents with MACE incidence in CAD cases. A prospective cohort study was conducted in both types of CAD (acute coronary syndrome (ACS) and chronic coronary syndrome (CCS)). The NT-proBNP levels were measured pre- and post-PCI using fluorescence immunoassay, while MACE was assessed three months post-PCI. The Student t-test was used to compare the levels of NT-proBNP between pre- and post-PCI and between those who had MACE and did not; both in patients treated with single or multiple stenting groups. A total of 32 CAD patients were recruited, consisting of 20 ACS cases and 12 CCS cases. NT-proBNP levels post-PCI increased significantly in both ACS and CCS patients compared to pre-PCI either among those treated with single and multiple stentings. MACE occurred in 4 (12.5%) out of a total of 32 patients, all of which occurred in ACS patients treated with multiple stentings. Those who had MACE had higher post-PCI NT-proBNP levels compared to those who did not have MACE (23,703.50 vs 11,600.17 pg/mL, p=0.013). This study highlights the association between elevated NT-proBNP levels and multiple stenting with the presence of MACE in CAD patients, particularly in ACS cases.

Nicotine is associated with smoking dependence and vascular inflammation through cotinine: A mediation analysis.

INTRODUCTION: The main alkaloid component in cigarettes is nicotine. Cotinine, a metabolite of nicotine, is capable of causing dependence effects through endless mechanisms modulated by the ion channel nicotinic acetylcholine receptors nAChRs. Nicotine and cotinine can also cause damage to blood vessels through a chronic inflammatory process mediated by the Ligand-Tie2 Angiopoietin Receptor system. Hypoxic conditions that occur due to vascular inflammation cause a decrease in the concentration of nitric oxide (NO). This study aimed to evaluate the relationship between NO levels and cotinine through the expression of nAChRs that mediate the nicotine dependence mechanism and Tie2 (Tyrosine Kinase 2) expression. METHODS: A cross-sectional study was conducted with 200 participants grouped into two groups based on their smoking status: 100 smokers and 100 non-smokers. All participants were men aged 20-40 years with no history of cardiovascular disease, diabetes mellitus, or dyslipidemia, and were not currently on medication. According to the parameters used, all blood samples were taken from peripheral blood for analysis using the ELISA kit or Colorimetric Assay Kit. RESULTS: Cigarette consumption increases blood cotinine concentrations in smokers and causes dependence by modulating nAChRs. The study indicates an emerging cycle regarding nicotine-cotinine consumption and nAChRs expression. In addition, the data in this study showed a significant relationship (p<0.001) regarding the cycle formed with decreased NO levels as a result of damage caused by Tie2-mediated inflammation. CONCLUSIONS: There is a relationship between NO levels and cotinine through nAChRs, which mediate the nicotine dependence mechanism and Tie2 expression.

Ascorbic Acid vs Calcitriol in Influencing Monocyte Chemoattractant Protein-1, Nitric Oxide, Superoxide Dismutase, as Markers of Endothelial Dysfunction: In Vivo Study in Atherosclerosis Rat Model.

Introduction: Ascorbic acid and calcitriol were frequently utilized in conjunction as therapy during the COVID-19 pandemic, and individuals with minor symptoms had notable improvements. There have been a few studies, often with conflicting findings, that examine the use of them for endothelium restoration and numerous clinical trial studies that failed to establish the efficacy. The aim of this study was to find the efficacy of ascorbic acid compared to calcitriol on the inflammatory markers monocyte chemoattractant protein-1 (MCP-1), nitric oxide (NO), and superoxide dismutase (SOD), as protective agents which play an important role in the early stages of atherosclerosis formation. This study was an experimental in vivo study. Methods: The total of 24 male Rattus norvegicus strain Wistar rats were divided into 4 groups, namely: control/normal group (N), atherosclerosis group (DL) given atherogenic diet, atherosclerosis group given atherogenic diet and ascorbic acid (DLC), and atherosclerosis group given atherogenic diet and calcitriol (DLD) treatment for 30 days. Results: Ascorbic acid and calcitriol treatment was significantly effective (P<0.05) in lowering expression of MCP-1 and increasing NO and SOD level. Calcitriol was superior to ascorbic acid in increasing SOD (P<0.05). There was no significant difference between ascorbic acid and calcitriol in decreasing MCP-1 and increasing NO (P>0.05). Discussion: Both treatments could reduce MCP-1, and increase NO and SOD by increasing antioxidants. In this study calcitriol was superior to ascorbic acid in increasing SOD, but not NO and decreasing MCP-1. According to the theory, it was found that calcitriol through nuclear factor erythroid 2-related factor 2 (Nrf2) causes a direct increase in the amount of SOD. Nrf2 is an emerging regulator of cellular resistance to oxidants. Conclusion: Ascorbic acid and calcitriol treatment was able to reduce MCP-1 and increase NO and SOD in atherosclerosis rat. Calcitriol was significantly superior in increasing SOD levels compared to ascorbic acid.

Correlation between high sensitivity C reactive protein (Hs-CRP) and neutrophil-to- lymphocyte ratio (NLR) with functional capacity in post COVID-19 syndrome patients.

Post coronavirus disease 2019 (COVID-19) syndrome is one of the causes of reduced functional capacity and work productivity, in particular for healthcare workers. The pathophysiology of the post COVID-19 syndrome is related to complex and multisystem inflammatory mechanisms, and cardiopulmonary exercise rehabilitation program is one of the efforts to improve the recovery process for patients with post COVID-19 syndrome. The aim of this study was to determine the correlation between the level of high sensitivity C-reactive protein (Hs-CRP) and neutrophil-to-lymphocyte ratio (NLR) with functional capacity (VO2max) in individuals with post-COVID-19 syndrome who received moderate- and high-intensity supervised cardiopulmonary exercise. A prospective cohort study was conducted at the Integrated Cardiac Rehabilitation Center of Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia. The supervised cardiopulmonary exercise was conducted for six weeks according to the participant's baseline VO2max. Spearman's and Pearson's correlation tests were used to assess the correlations. A total of 30 individuals (19 and 11 had moderate and high intensity exercise, respectively) were involved in this study. At moderate intensity exercise, the average Hs-CRP and NLR were 3.3 mg/L and 1.99, respectively; while at high intensity, the values were 3.8 mg/L and 1.79, respectively. No significant correlation between Hs-CRP level and functional capacity in both moderate-intensity and high intensity groups. In contrast, NLR was negatively correlated with functional capacity (r=-0.545, p=0.016) in moderate intensity exercise group. In conclusion, NLR value was negatively correlated with functional capacity in individuals with post-COVID-19 syndrome after receiving moderate intensity supervised cardiopulmonary exercise program. Therefore, moderate intensity of cardiopulmonary exercise maybe be used as a program to accelerate the recovery for those with post COVID-19 syndrome.

Association between six-minute walk distance and prognosis of atherosclerotic coronary heart disease post-cardiac rehabilitation.

Plaque accumulation in the coronary arteries is a major cause of coronary heart disease (CHD), a disease infamously known as a contributor for global death burden. Major adverse cardiac events (MACE) pose significant risks for CHD patients, highlighting the urgency of effective management and cardiac rehabilitation in CHD management. Studies have reported the role of the six-minute walk distance (6MWD) test in predicting outcomes for CHD patients; however, none have performed the investigation in Aceh setting. The aim of this study was to investigate the reliability of 6MWD as a prognostic factor for post-cardiac rehabilitation of patients with atherosclerotic CHD. A cross-sectional study was conducted in Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia. MACE was determined through in-person interviews, and phone calls with 30 atherosclerotic CHD patients who completed cardiac rehabilitation between August 2018 and September 2020. The association between 6MWD and prognosis, assessed by MACE incidence, was calculated. The results revealed that 6MWD was strongly associated with MACE occurrence during post-cardiac rehabilitation (p=0.029; prevalence ratio 4.5). Furthermore, CHD patients achieving 6MWD of more than 300 meters exhibited a lower incidence of MACE (10.5%) than patients with 6MWD of less than 300 meters (45.5%). In conclusion, the present study sheds light on the importance of improving functional capacity in patients with atherosclerotic CHD post-cardiac rehabilitation due to its significant association with the prognosis.

The association between vesicle-associated membrane protein - 8 A/G gene polymorphism and the risk of acute myocardial infarction / La relación entre el polimorfismo A/G del gen de la proteína de membrana asociada a vesículas-8 y el riesgo de infarto agudo de miocardio

Abstract Introduction Until now, only few studies have reported the correlation between vesicle-associated membrane protein-8 (VAMP-8) A/G gene polymorphism and acute myocardial infarction. Whereas, theoretically, VAMP-8 plays a pivotal role in the pathogenesis of acute myocardial infarction through platelet activation, secretion, and aggregation. Objective To investigate the association between VAMP-8 A/G gene polymorphism and the risk of acute myocardial infarction. Methods A cross-sectional study was carried out at Saiful Anwar General Hospital during June 2013 - May 2014. A Mae II enzyme with restriction fragment length polymorphism method was used to genotype VAMP-8 A/G gene polymorphisms in acute myocardial infarction and control groups. A multiple logistic regression test was used to analyze the association between VAMP-8 A/G gene polymorphism and the risk of acute myocardial infarction. Results A total of 35 controls and 97 acute myocardial infarction patients from our Hospital during the period were enrolled for our study. Our results found that VAMP-8 A/G gene polymorphism was not associated with the risk of acute myocardial infarction. Moreover, we also failed to confer the association between VAMP-8 A/G gene polymorphism and both smoking and hypertension among patients with acute myocardial infarction. Furthermore, in the setting of premature acute myocardial infarction, the correlation also failed to confirm. Conclusion In our population, there is no association between VAMP-8 A/G gene polymorphism and the risk of acute myocardial infarction.

Resumen Introducción Hasta la fecha, solo unos pocos estudios han reportado la correlación entre el polimorfismo A/G del gen de la proteína de membrana asociada a vesículas-8 (VAMP-8, por sus siglas en inglés) y el infarto agudo de miocardio. Si bien, en teoría, VAMP-8 juega un papel fundamental en la patogénesis del infarto agudo de miocardio a través de la activación, secreción y agregación plaquetaria. Objetivo Investigar la relación entre el polimorfismo A/G del gen VAMP-8 y el riesgo de infarto agudo de miocardio. Métodos: Se llevó a cabo un estudio transversal en Siful Anwar General Hospital entre junio del 2013 y mayo del 2014. Se utilizó la técnica de polimorfismos de longitud de fragmentos de restricción con la enzima Mae II para genotipificar los polimorfismos A/G del gen VAMP-8 en grupos de infarto agudo de miocardio y de control. Se aplicó una prueba de regresión logística múltiple para analizar la relación entre el polimorfismo A/G del gen VAMP-8 y el riesgo de infarto agudo de miocardio. Resultados Se incluyeron un total de 35 controles y 97 pacientes con infarto agudo de miocardio de nuestro Hospital durante el periodo del estudio. Nuestros resultados encontraron que el polimorfismo A/G del gen VAMP-8 no estaba relacionado con el riesgo de infarto agudo de miocardio. Por otra parte, tampoco pudimos establecer una relación entre el polimorfismo A/G del gen VAMP-8 y tanto tabaquismo como hipertensión en pacientes con infarto agudo de miocardio. Asimismo, en el contexto de infarto agudo de miocardio prematuro, tampoco se confirmó la correlación. Conclusión: En nuestra población, no existe una relación entre el polimorfismo A/G del gen VAMP-8 y el riesgo de infarto agudo de miocardio.

Expression of Hypoxia-Inducible Factor-1α (HIF1A) and Lp-PLA2 in Low, Intermediate, and High Cardiovascular Disease Risk Population.

BACKGROUND: The pathomechanism of CVD is a complex and multifactorial process. The primary mechanism of CVD is atherosclerosis. Inflammation in atherogenesis raises the risk of hypoxia, which will activate hypoxia-inducible factor-1α (HIF1A). Also, together with lipoprotein-associated phospholipase A2 (Lp-PLA2), an inflammatory mediator for atherogenesis. PURPOSE: This study aims to measure the hypoxia-inducible factor-1α (HIF1A) expression and its correlation to Lp-PLA2 expression at low-risk, intermediate, and high-risk CVD populations. PATIENTS AND METHODS: The study used a correlational analysis method with a total sampling technique in 160 individuals in the risk population. The atherosclerosis risk group was analyzed using the Framingham Risk Score and categorized into low, intermediate, and high-risk groups. Venous blood samples taken from respondents were measured using the ELISA method with Lp-PLA2 and HIF-1α as parameters. Data were analyzed using normality test, homogeneity test, one-way ANOVA, post hoc-Tukey HSD, and Pearson correlation. RESULTS: The concentration of HIF1A had a very strong correlation with Lp-PLA2 expression, both in the low-risk group (r = 0.512), intermediate (r = 0.512), and high (r = 0.715) (P <0.05). However, the concentrations of Lp-PLA2 did not match the FRS. CONCLUSION: HIF1A expression increased with increasing risk, while Lp-PLA2 expression decreased with increasing risk of atherosclerosis based on the FRS category. There is a significant correlation between HIF1A expression and Lp-PLA2 expression based on FRS.

Decreasing angiogenesis vasa vasorum through Lp-PLA2 and H2O2 inhibition by PSP from Ganoderma lucidum in atherosclerosis: in vivo diabetes mellitus type 2.

Background Type 2 diabetes mellitus (T2DM) is a major risk factor of atherosclerosis. Hyperglycemia in T2DM causes advanced formation of glycation end products (AGE) which leads to oxidative stress and chronic inflammation. Oxidative stress occurs due to increased levels of reactive oxygen species (ROS) such as H2O2. On the other hand, lipoprotein-associated phospholipase (Lp-PLA2) has pro-inflammatory effects, which cause instability of atherosclerosis plaques. This condition causes hypoxemic cells to stimulate HIFα induced vasa vasorum angiogenesis. This study aims to understand the potential of PSP as an anti-angiogenic agent through decreased levels of H2O2 and Lp-PLA2 leading to the decline of vasa vasorum angiogenesis in diabetic rat model. In addition, this study also measured the lipid profile of diabetic rat model in relation to vasa vasorum angiogenesis. Methods True laboratory experiment with randomized post-test control of group design using 25 wistar rats (Rattus norvegicus) were divided into five groups; one normal group and four group with High Fat Diet (HFD) and low dose streptozotocin (30 mg/kgBW) injection sc, treated with placebo and three various doses of PSP 50, 150, 300 mg/kgBW. Results ANOVA test (p < 0.05) shows that there is a significant influence of polysaccharide peptide (PSP) feeding on the decreased amount of vasa vasorum angiogenesis (p = 0.00), lipid profile (cholesterol total and triglyceride; p = 0.01, p = 0.001), and amount of H202 (p = 0.003). The amount of Lp-PLA2 declined to (p = 0.184). This result indicates that PSP prevents inflammation in atherosclerosis. Conclusions PSP of Ganoderma lucidum is an anti-angiogenic agent in T2DM.

Phospholipase A2 is an Inflammatory Predictor in Cardiovascular Diseases: Is there any Spacious Room to Prove the Causation?

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme family of phospholipase A2 produced by the inflammatory cell in atherosclerotic plaque. It is transported in the circulation, attached mainly to low-density lipoprotein-cholesterol (LDL-C). It hydrolyzes glycerophospholipids particularly fatty acids at the sn-2 position and produces numerous bioactive lipids; and leads to endothelial dysfunction, atherosclerotic plaque inflammation, and development of the necrotic core in plaques. There are two kinds of phospholipase A2, namely: secretory phospholipase A2 (sPLA2) and Lp- PLA2. They are deemed as evolving predictors of cardiovascular disease (CVD) risk in hospitaland population-based studies, including healthy subjects, acute coronary syndromes (ACS) and patients with CVD. Unfortunately, Lp-PLA2 inhibitor (darapladib) and s-PLA2 inhibitor (varespladib methyl) failed to prove to lower the risk of composite CVD mortality, myocardial infarction and stroke in those with stable CVD and ACS. Herein, we describe the explanation based on the existing data why there is still a discrepancy among them. So, it highlights the opinion that phospholipase A2 is merely the inflammatory biomarkers of CVD and playing an important role in atherosclerosis. Further, there is more spacious room to prove the causation.

Comparison of major bleeding in patients with acute coronary syndrome that underwent coronary artery bypass grafting treated with clopidogrel or ticagrelor: a systematic review and meta-analysis.

Background: There is controversy among physicians regarding the use of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients treated with coronary artery bypass grafting (CABG). Moreover, the evidence of previous studies about this topic remained inconclusive. This study aimed to perform a meta-analysis concerning the relation between the risk of major bleeding and the use of different DAPT (clopidogrel or ticagrelor) in ACS patients treated with CABG. Methods: A meta-analysis was conducted during March to October 2019. Searches were carried out in Pubmed, Embase, Cochrane, and Web of Science. The predictor covariate in our present study was DAPT (clopidogrel or ticagrelor), and the outcome measure was the risk of major bleeding. Sub-group analysis was also performed, where data were classified into pre- and post-CABG. Furthermore, to determine the correlation and effect estimation, data were analyzed using fixed or random effect model. Results: A total of 13 studies consisting 34,015 patients treated with clopidogrel and 32,661 patients treated with ticagrelor was included in our study. Our pooled calculation revealed that the incidence of major bleeding was not different significantly between clopidogrel and ticagrelor. In pre- and post-CABG sub-groups, our results also found no significant difference in major bleeding incidence between clopidogrel and ticagrelor groups. Conclusions: Our meta-analysis clarifies that clopidogrel, compared to ticagrelor, or vice versa, is not associated with the risk of major bleeding in ACS patients treated with CABG.

Lp-PLA2 Selective Inhibitor (Darapladib) Effect In Lowering The Expression Level Of IL-1B And IL-6 In The Renal At Type 2 Diabetes Mellitus.

PURPOSE: The aim of this study is to prove that type 2 diabetes mellitus can induce increasing inflammation marker in renal and that the provision of darapladib as Lp-LA2 Inhibitor agents can inhibit inflammation that were measured from the expression of IL-1B and IL-6- type cytokine in renal. This study also discusses the correlation between IL-1B and IL-6- type cytokine expression in renal. METHODS: Thirty Sprague-Dawley (SD) rats were divided into three main groups; those are negative control group (NC), Type 2 Diabetes Mellitus group (T2DM) given high fat diet (HFD) with streptozotocin intraperitoneal injection (35mg/kg BW) and diabetes mellitus + darapladib group (DM + DP). Each group was treated within two serial treatment time: 8 weeks and 16 weeks. Expressions of IL-1B and IL-6- type cytokine in renal were the markers that we measured by immunofluorosense method. RESULTS: The administration of darapladib can significantly decrease the expression of IL-1B- type cytokine (p ANOVA = 0.029, p < 0.005) measured in rats' renal both at weeks 8 and 16 in the T2DM group. The Expression of IL-6- type cytokine also showed a significant difference after treated with darapladib both at weeks 8 and 16 in T2DM group with p-value of ANOVA = 0.033, p < 0.005. The Pearson correlation showed a strong correlation (linear regression value was r2 = 0.743). CONCLUSION: Our results show that atherosclerosis caused by inflammation in renal T2DM SD rats could be inhibited by the administration of darapladib.

Polysaccharide peptide (PsP) Ganoderma lucidum: a potential inducer for vascular repair in type 2 diabetes mellitus model.

INTRODUCTION: The increasing blood glucose level due to insulin resistance which occurs in diabetes mellitus (DM) may cause vascular damage. This study aims to prove the effect of the polysaccharide peptide (PsP) Ganoderma lucidum on improving vascular damage through an increase of circulating endothelial cells and circulating endothelial cells (CEC) ratio, decreased H2O2, triglyceride (TG), total cholesterol (TC) and insulin resistance in type 2 DM. METHODS: Our study is a true experimental study with randomized posttest control group design that used 35 Wistar rats divided into five groups: normal, control (+) and three groups of different variant PsP doses 50, 150 and 300 mg/kg BW (n=7). RESULTS: By using one-way ANOVA and post-hoc Duncan test, the results show a significant increase of endothelial progenitor cell (EPC) concentration (p=0.000) and ratio EPC:CEC (0.000) by dose-dependent fashion and also reduced CEC concentration (p=0.001), H2O2 (p=0.03), TG (p=0.001), TC (p=0.01) and insulin resistance (p=0.003). CONCLUSION: In this study, PsP induced endothelial repairing process and reduced the risk factor with 300 mg/kg BW as optimum dose. However, further research on EPC and CEC detection markers is important. Further research on PsP and clinical trial for commercial uses is also needed.

The Gene Polymorphism of Angiotensin-Converting Enzyme Intron Deletion and Angiotensin-Converting Enzyme G2350A in Patients With Left Ventricular Hypertrophy: A Meta-analysis.

OBJECTIVES: The aim of the study was to evaluate the correlation between left ventricular hypertrophy and the gene polymorphism of angiotensin-converting enzyme (ACE) intron deletion (I/D) and ACE G2350A. METHODS: Information related to the sample size and genotype frequencies was extracted from each study. RESULTS: Our results found that the D allele (p = 0.0180) and DD genotype (p = 0.0110) of ACE I/D had a significant association with increasing the risk of left ventricular hypertrophy, whereas the I allele (p = 0.0180), but not II (p = 0.1660) and ID genotypes (p = 0.1430), was associated with decreasing the risk of left ventricular hypertrophy. On other hand, we found that the A allele (p = 0.0020) and GA genotype of ACE G2350A (p = 0.0070) had the correlation with increasing the risk of left ventricular hypertrophy. CONCLUSIONS: Our meta-analysis reveals that the D allele of ACE I/D and the A allele of ACE G2350A are associated with increasing the risk of left ventricular hypertrophy.

Dietary Ethanolic Extract of Mangosteen pericarp Reduces VCAM-1, Perivascular Adipose Tissue and Aortic Intimal Medial Thickness in Hypercholesterolemic Rat Model.

BACKGROUND: High-fat diet (HFD) is associated with dyslipidemia which is a risk factor for atherosclerosis. Dyslipidemia causes oxidative stress which induces vascular cell adhesion molecule-1 (VCAM-1). Oxidative stress also triggers the thickening of tunica intima-media (IMT) and Perivascular Adipose Tissue (PVAT). Xanthone compound in ethanolic extract of Mangosteen pericarp (EEMP) has an antioxidant property to overcome the oxidative stress. AIM: The objective of this study is to investigate the effect of dietary EEMP administration on the expression of VCAM-1 and thickness of PVAT and IMT in atherosclerotic rat model fed with HFD. METHODS: This experimental laboratory study uses 25 Wistar strain Rattus norvegicus which were divided into 5 study groups. Negative Control group (GT1) was given a normal diet, Positive Control group (GT2) was treated with HFD, and three treatment groups were each treated with HFD with Mangosteen pericarp extract of 200 mg/kg BW (GT3), 400 mg/kg BW (GT4), and 800 mg/kg BW (GT5). Measurements of VCAM-1 expression were performed using immunofluorescence. PVAT and IMT measurements were performed on rat aortic preparations. RESULTS: One-way ANOVA test showed the addition of dietary EEMP significantly (p < 0.05) decreased the expression of VCAM-1 and decreased the thickness of PVAT and IMT in treatment groups as compared with both negative and positive controls. Tukey HSD test showed a dose of 800 mg/kg BW was the most effective dose for decreasing VCAM-1 level, PVAT and IMT. CONCLUSION: Dietary EEMP significantly decreases the expression of VCAM-1, as well as the thickness of PVAT and IMT in Wistar strain Rattus norvegicus treated with HFD.

Exploration of Adhesion Molecule Expression in Cardiac Muscle of Early Atherosclerosis Dyslipidemic Sprague Dawley Rats.

OBJECTIVE: This study is aimed to examine the expression of ICAM-1 and VCAM-1 in cardiac tissue of dyslipidemic Sprague Dawley rats. METHODS: Eight Sprague Dawley strain rats, with 150-200 gram body weight, were divided into two groups. The control group was fed a standard diet, the positive control group was fed a high-fat diet as our previous study for 8 weeks. The pattern of distribution of ICAM-1 and VCAM-1 in cardiac muscle cell was examined by immunofluorescence and observed with a confocal laser scanning microscope. Lipid profile was also examined at the end of the study. RESULT: Independent t-test showed no differences in ICAM-1 and VCAM-1 expression in cardiac muscle of hypercholesterol-diet-fed Sprague Dawley rat compared to control. CONCLUSION: The expression of ICAM-1 and VCAM-1 in cardiac muscle did not change after the onset of atherosclerosis.

Reduction in Vasa Vasorum Angiogenesis by Lp-PLA2 Selective Inhibitor Through The HIF-1α and VEGF Expression Under Dyslipidemic Conditions in Atherosclerosis Pathogenesis.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease which may lead to major cardiovascular events. The primary cause of atherosclerosis is Dyslipidemia. The increased level of lipid profile triggers endothelial dysfunction. This results in inflammation with the recruitment of monocyte, macrophage, T lymphocyte, and Mast cells secreted by an Lp-PLA2 enzyme which causes binding between macrophage and oxidized LDL. This binding results in the formation of foam cells and also the migration of smooth muscle cells. Following that, an Lp-PLA2 receptor hydrolizes OxPC which results in LysoPC and OxNEFA, bioactive compounds which stimulate the progression of atherosclerosis plaques. This process leads to cell hypoxia, which may result in the increase of HIF-1α and VEGF expressions and induction of vasa vasorum angiogenesis. Employing darapladib as an agent of Lp-PLA2 selective inhibitors, this study aimed to find out the effect of darapladib as an Lp- PLA2 selective inhibitor agent on the formation of vasa vasorum angiogenesis and the decrease of HIF-1α and VEGF expression in aortic tissue of rats with dyslipidemia. METHOD: A true laboratory experiment with a randomized post-test control group design used 30 male spraque dowley rats as animal models which were divided into 6 groups: Normal 8 weeks, Normal 16 weeks, Dyslipidemia (DL) 8 weeks, Dyslipidemia (DL) 16 weeks, Dyslipidemia with darapladib treatment (DLDP) 8 weeks and Dyslipidemia with darapladib treatment (DLDP) 16 weeks. The data measured in this study were the lipid profile (total cholesterol, HDL, and LDL). Using EnzyChrom TM kit, hematoxylin eosin, and double-labelling immunofluorescene, the levels of lipid profile, vasa vasorum, HIF-1α and VEGF were measured. RESULTS: The study results which were analyzed using NOVA test showed that with darapladib administration, there was a significant decrease in vasa vasorum angiogenesis (p=0.000), HIF-1α (p=0.005) and VEGF (p=0.009) expression in each time series. This result proves that Lp-PLA2 inhibitor reduces inflammatory process. CONCLUSION: Darapladib injection as an Lp-PLA2 selective inhibitor correlates with the decreasing vasa vasorum angiogenesis through alteration in HIF-1α and VEGF expressions in the aorta of high fat diet rats. We recommend further experiments to determine the effectiveness of darapladib with earlier time series in the atherosclerosis process.

Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model.

OBJECTIVE: Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley rat model. METHODS: Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining. RESULTS: Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p<0.05) in the foam cells number and iNOS and ICAM-1 expression in aorta compared to controls after both treatment times. Darapladib treatment significantly reduced (p<0.05) foam cells number as well as iNOS expression in aorta in rats with T2DM after both treatment times. A significant decrease (p<0.05) in ICAM-1 expression in aorta was observed after darapladib treatment in rats with T2DM only after 8 weeks of treatment. CONCLUSION: Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM rat model.

The predictors of no reflow phenomenon after percutaneous coronary intervention in patients with ST elevation myocardial infarction: A meta-analysis.

OBJECTIVE: To investigate the no reflow risk factors after percutaneous coronary intervention in ST elevation myocardial infarction patients. METHOD: Sample size, mean±standard deviation (SD) or frequencies (percent) of normal and no reflow groups were extracted from each study. RESULTS: Of 27 retrospective and prospective studies, we found that increasing risks of no reflow were associated with advanced age, male, family history of coronary artery disease, smoking, diabetes mellitus, hypertension, delayed reperfusion, killip class ≥2, elevated blood glucose, increased creatinine, elevated creatine kinase (CK), higher heart rate, decreased left ventricular ejection fraction (LVEF), collateral flow ≤1, longer lesion length, multivessel disease, reference luminal diameter, initial thrombolysis in myocardial infarction (TIMI) flow, and high thrombus burden. Moreover, initial TIMI flow ≤1 and high thrombus burden had the greater impact on no reflow (OR95%CI=3.83 [2.77-5.29], p<0.0001 and 3.69 [2.39-5.68], p<0.0001, respectively). CONCLUSION: Our meta-analysis reveals that initial TIMI flow ≤1 and high thrombus burden are the most impacted no reflow risk factors.

The inhibitory effects of polysaccharide peptides (PsP) of Ganoderma lucidum against atherosclerosis in rats with dyslipidemia.

BACKGROUND: Atherosclerosis occurs as a result of low-density lipoprotein (LDL) deposits oxidation. Endothelial dysfunction is an early process of atherosclerosis. Restoring endothelial lining back to normal by endothelial progenitor cells (EPCs) is critical for slowing or reversing vascular disease progression. Oxidative stress from hydrogen peroxide (H2O2) is increased in dyslipidemia so that antioxidant agent is required to prevent destruction of blood vessels. OBJECTIVES: This study aims to report Ganoderma lucidum polysaccharide peptide (PsP) effects in atherogenic process by measuring H2O2 level, IL-10 level, and EPC number in blood serum, and also intima-media thickness of aorta in dyslipidemia Wistar rat model by giving them a hypercholesterol diet (HCD). MATERIALS AND METHODS: The study was an experimental in vivo post-test with control group design. Thirty-five Wistar rats (Rattus norwegicus) were divided into five groups (normal diet group, HCD group, and hypercholesterol groups that received 50 mg/kg, 150 mg/kg, and 300 mg/kg bodyweight PsP). RESULTS: Each treatment group showed significant results for the administration of PsP using the one-way analysis of variance test (p<0.050) for the reduction of H2O2 (p = 0.003), levels of IL-10 (p = 0.027), number of EPC in the blood serum (p = 0.011), and the intima-media thickness of the aorta (p = 0.000). PsP from G. lucidum is a potent antioxidant and may prevent atherogenesis process in patients with dyslipidemia. CONCLUSIONS: The optimum doses of PsP in this study is 300 mg/kg bodyweight. Further studies are required to determine the antioxidant effects of PsP G. lucidum and its benefits in the management of dyslipidemia.