scholarly journals Regulation of microRNA-33, SREBP and ABCA1 genes in a mouse model of high cholesterol

2021 ◽  
Vol 64 (1) ◽  
pp. 103-108
Author(s):  
Xianglun Zhang ◽  
Hongbo Zhao ◽  
Qingkai Sheng ◽  
Xiaomu Liu ◽  
Wei You ◽  
...  

Abstract. MicroRNAs are short non-coding RNAs that regulate gene expression. Several microRNAs, useful for coronary artery disease assessment, have previously been identified. MicroRNA-33 is located within SREBP introns and controls cholesterol homeostasis. In order to find the possibility of microRNA-33 as a potential biomarker in high cholesterol disease, we developed a mouse model for coronary heart disease by feeding mice with a high-fat diet. The expression differences of microRNA-33, SREBP and ABCA1 genes in the liver, muscle, and lipid tissues were compared between a high-cholesterol group and control group in mice. The results showed that ABCA1 was up-regulated by high cholesterol conditions in liver, muscle and lipid tissues. SREBP1C was up-regulated by high cholesterol conditions in the liver and lipid tissues and down-regulated by high cholesterol conditions in the muscle tissue. MicroRNA-33 and SREBP2 were down-regulated by high cholesterol conditions in the liver and muscle tissues and up-regulated by high cholesterol conditions in the lipid tissue. Our study suggests that antisense therapeutic targeting of microRNA-33 may be a potential biomarker for cardiovascular disease.

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Pradyumna Agasthi ◽  
Sivakanth Aloor ◽  
Avantika Chenna ◽  
Anekwe Onwuanyi

Background: Ghrelin (GH) is a gastrointestinal endocrine peptide regulating multiple biological processes including adipogenesis, glucose metabolism, cell differentiation and proliferation. Recent studies demonstrated that GH inhibits pro-atherogenic changes in vessel wall via inhibition of nuclear factor - B activity, a transcriptional factor mediating production pro-inflammatory cytokines and adhesion molecule expression in the endothelium. The aim of the current study is to conduct a meta-analysis to evaluate the relationship between serum GH levels and coronary artery disease (CAD). Methods: We searched MEDLINE, CINHAL and COCHRANE databases for studies reporting serum GH levels in the CAD and non CAD study population. We included case controls, cohort and cross-sectional studies. We calculated the weighted standardized mean difference (SMD) in serum GH levels between the CAD and control groups. Results: Our search strategy yielded 285 articles and we included 10 studies enrolling 1855 participants. The median age of the CAD group was 62 yrs. (IQR 60 - 63) compared to 61 yrs. (IQR 58 - 65) in the control group. The median body mass index in the CAD group was 28 kg/m2 (IQR 27.9 - 28) compared to 27 kg/m2 (IQR 26 - 27) in the control group. The unweighted median serum GH levels in the CAD group were 0.66 ng/ml (IQR 0.3 - 1.6) compared to 0.76 ng/ml (IQR 0.38 - 4.9) in the control group. The SMD of GH level was -0.44 (95% CI -0.56,-0.31) p<0.001 comparing those in the CAD group and control group. Conclusion: Serum GH levels are significantly and inversely associated with CAD. Current findings warrant the need to further investigate the role of GH in the pathogenesis of CAD.


2018 ◽  
Vol 17 (2) ◽  
pp. 290-295
Author(s):  
Premtim Rashiti ◽  
Ibrahim Behluli ◽  
Albiona Bytyçi

Objective: By enrolling a prospective study of 82 patients that underwent non-urgent coronary angiography for coronary artery disease (CAD), it is aimed to investigate the correlation between adiponectin and waist-hip-ratio with severity of CAD.Materials and methods: The results of the angiography, divided the patients into two groups, patients admitted with a diagnosis of CAD and non-CAD. In the conducted hospital based research, two groups were involved: the study group with documented angiographically CAD and control group without angiographic evidence of CAD. Some of the baseline adiponectin levels in stored serum samples of all patients, anthropometric and biochemical risk factors were assessed in both groups.Result and discussion: As the result, we have seen the presence of CAD that was associated with current smoking, male gender, waist–hip ratio (WHR).While, no significant difference between median adiponectin levels at baseline were observed between cases and controls.Conclusion: There is a significant positive correlation between waist - hip ratio and presence of severity of coronary artery disease.Bangladesh Journal of Medical Science Vol.17(2) 2018 p.290-295


2013 ◽  
Vol 35 ◽  
pp. 97-103 ◽  
Author(s):  
Chiyan Zhou ◽  
Jia Cao ◽  
Liang Shang ◽  
Chuanfeng Tong ◽  
Hanling Hu ◽  
...  

Paraoxonase-1 (PON1), a high-density-lipoprotein- (HDL-) associated enzyme, has the potential to protect against atherogenesis. We examine the relationships between plasma PON1 activity and the progression of atherosclerosis as well as coronary artery disease (CAD). Fasting blood samples were collected from female apolipoprotein E-deficient (apoE−/−) mice and 149 patients undergoing coronary angiography for the biochemical parameters measurement. The severity of CAD was defined using angiographic Gensini score (GSS). Compared to 3-month-old apoE−/−mice, aged mice had significantly lower PON1 activity, which is negatively correlated with the size of atherosclerotic lesion and plasma interleukin-6 (IL-6) and tumor necrosis factorα(TNF-α) levels. In study patients, PON1 activity was correlated with age, sex, and HDL-cholesterol, apolipoprotein AI, and high-sensitivity C-reactive protein (hs-CRP) levels and was significantly lower in CAD group than that in non-CAD control group. Interestingly, PON1 activity in severe CAD group (GSS > 40) was further significantly reduced compared to those in mild and moderate subgroups (GSS  ≤ 40) (P<0.01). There is a significant correlation between PON1 activity and the severity of CAD as assessed by GSS (r=-0.393,P<0.001). PON1 activity may be a potential biomarker for the severity of CAD.


Author(s):  
Fatemeh Vafashoar ◽  
Kazem Mousavizadeh ◽  
Hadi Poormoghim ◽  
Abbas Tavasoli ◽  
Tahereh Musavi Shabestari ◽  
...  

Systemic sclerosis is a fibrotic autoimmune disease in which aberrant remodeling of the extracellular matrix in organs disturbs their functionalities. The aim of this study was to investigate the expression of gelatinases on systemic sclerosis. Consequently, a mouse model of systemic sclerosis was employed and the gelatinolytic activity of gelatinases was evaluated on the fibrotic tissues of this model. Two groups of ten mice were considered in this work: a group of systemic sclerosis model and control group. For the generation of systemic sclerosis model, mice received bleomycin, while the control group was subjected to phosphate buffered saline (PBS) reception. Mice were tested for fibrosis by using trichrome staining, hydroxyproline measurement and α-SMA detection in tissue sections. Additionally, the gelatinolytic activity of matrix metalloproteinase 2 and matrix metalloproteinase 9 were measured using gelatin zymography in lungs and skin tissue homogenates. The obtained results indicated that subcutaneous injection of bleomycin-induced fibrosis in skin and lung tissues of mice. Pro and active forms of matrix methaloproteinase 9 were increased in fibrotic lung tissues (p<0.05 and p<0.01, respectively), while, the gelatinolytic activity of MMP2 was unaffected in these tissues. Additionally, in skin tissues of bleomycin-treated animals, both pro and active forms of MMP9 and MMP2 were increased (p<0.05). Pro and active forms of gelatinases increase differently in skin and lung tissues of bleomycin-induced scleroderma.  


2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
D Vorobyeva ◽  
TYU Rebrova ◽  
SA Afanasyev ◽  
VV Ryabov

Abstract Funding Acknowledgements Type of funding sources: None. Background We hypothesized that MINOCA patients have distinctive features of sympatho-adrenal system (SAS) activation in comparison with patients with stenosis atherosclerosis which can play a significant role in the development of ischemic events at the time of the index hospitalization and after 1 year. Aim To study the parameters of β-adrenoreception of cell membranes in patients with MINOCA compared with patients with AMI and single-vessel coronary artery disease after 1 year. Material and methods: The study is non-randomized open controlled. Adrenergic reactivity of the body was assessed by the method for assessing the β-adrenergic reactivity of erythrocyte membranes (β-ARM) for studying the parameters of adrenergic reception of cell membranes. This parameter (β-ARM) was studied upon admission, at days 2, 4 and 7 and 1 year after AMI. The normal level of β- ARM &lt;20 rel.units. Results The study included 40 patients with AMI (19 patients in the main group and 21 patients in the control group). Three patients (15.7%) with diagnosed acute myocarditis were excluded from the analysis. The median age in the main and control groups was 66 (54; 70) years and 59 (55; 65) years, respectively. These groups were different at the admission in such parameters: in smoking frequency (31,3% vs 52.3%), history of angina pectoris (62,5% vs 28,5%), time of admission to the hospital (390 min. vs 180 min.) and thrombolytic therapy at the prehospital phase (3% vs 11%), p &lt; 0,05.  The median β-ARM in MINOCA patients upon admission was 41.7 (29.0; 61.5) rel. units, 1 day - 48.6 (38.5; 57.3) rel. units, 4 days - 49, 4 (39.0; 63.3) rel. units, 7 days - 53.5 (35.2; 67.7) rel. units, after 1 year - 35.7 (25.5; 42.6) rel. units. In the control group, the median β-ARM upon admission was 52.5 (25.4; 64.5) rel. units, 1 day –51.6 (28.3; 56.9) rel. units, 4 days - 48, 5 (34.9; 61.2) rel. units, 7 days - 45.1 (32.2; 68.9) rel. units, after 1 year - 20.8 (14.8; 29.3). In MINOCA patients β-ARM indices in the early postinfarction period statistically higher than the 1 year:  at  1, 2, 4 days, p &lt;0.05, on day 7 no differences were found (p = 0.34). A dynamic comparison of β-ARM indicators in the control group at the time of the index hospitalization and through 1 year revealed differences  at all days early postinfarction period, p &lt;0.05. In the control group, the β-ARM indicator reached normal values by 1-year follow-up period. In MINOCA patients, β-ARM indices after 1 year were statistically higher than in the control group, p = 0.008. Conclusions: The β - ARM indices in MINOCA patients after 1 year from the ischemic event are higher than in the control group. In dynamics, the β - ARM indices statistically decreased in the control group, but did’n change in MINOCA patients. Despite the use of a beta-blocker in MINOCA patients, increased SAS activity persists; therefore, β-APM values did’n change significantly after 1 year.


2020 ◽  
pp. 91-91
Author(s):  
M.J. Dzhumaeva ◽  
A.I. Tabarov ◽  
Kh.T. Fayzulloev

Background. Аn L-arginine is a conditionally essential amino acid. The daily average requirement is 4.2 mg. The L-arginine exhibits angioprotective properties, regulates proliferation and apoptosis, oxidative processes, blocks platelet aggregation and has a fibrinolytic effect ‒ antithrombotic (prevents the adhesion of circulating platelets and leukocytes) for anti-inflammatory effects. The likelihood of developing thrombotic complications in all patients with COVID-19 is very high, such patients are recommended to double dosage of anticoagulants. Objective. To study the combination of the anticoagulant therapy and the drug Tivortin in patients with coronary artery disease with COVID-19. Materials and methods. 28 patients with the cardiac ischemia of the exertion stenocardia functional class II-III with COVID-19 were examined. The patients were divided into the main and control groups. One of the groups, in addition to the anticoagulant therapy Clexan 2 times 0.6 mg, have taken the drug Tivortin, manufactured by “Yuria-Pharm” (Ukraine), containing L-arginine (4.2 mg). Results. The therapy with the use of the nitrate oxide donors in combination with the anticoagulants in the main group showed an increase in exercise tolerance, in the SpO2 level, i.e., a decrease in hypoxia in the main group compared with the control group. Conclusions. The addition of Tivortin to the therapy of anticoagulants that inhibit the activity of the blood coagulation system may increase the chances of survival of patients hospitalized with COVID-19.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Kee Ook Lee ◽  
Kyung-Yul Lee ◽  
Jae-Youn Kim ◽  
Cheol-Young Lee ◽  
Sang-Jun Na ◽  
...  

Introduction: Blood neutrophil/lymphocyte ratio (NLR) is a simple marker of subclinical inflammation that can be easily obtained. The NLR has recently emerged as a prognostic marker in patients with cancer and coronary artery disease. However, little is known about the role of NLR in patients with intracranial aneurysm (IA). Hypothesis: The purpose of this study was to determine the clinical significance of NLR in patients with IA. Methods: The study group consisted of patients with IA who had been admitted to the neurology department from January 2008 to December 2014. A total of 362 patients including 176 patients with unruptured IA, 186 patient with ruptured IA were enrolled in this study. The control group consisted of 178 age, sex-matched healthy adults who had not harbor IA by CTA, MRA, DSA. The baseline NLR was calculated as the ratio of neutrophil count to lymphocyte count. WBC count>12.000 cells per μL or <4.000 cells per μL and high body temperature>38 ° are excluded from the study. Results: The Mean NLR was significantly higher among persons with cerebral aneurysm compared with controls (P < 0.001). The level of NLR in ruptured IA group were found higher compared to unruptured IA and control group (7.0 ± 6.6 vs 2.5 ± 1.5 vs 1.6 ± 0.5, P < 0.001). Other comorbid conditions were balanced between these three groups. Conclusions: Higher NLR is associated with cerebral aneurysm. Unlike many other inflammatory markers and bioassays, NLR are inexpensive and readily available biomarkers that may be useful for risk stratification in patients with cerebral aneurysm.


Angiology ◽  
2018 ◽  
Vol 69 (8) ◽  
pp. 730-735 ◽  
Author(s):  
Vana Kolovou ◽  
Angelos Tsipis ◽  
Constantinos Mihas ◽  
Niki Katsiki ◽  
Vasiliki Vartela ◽  
...  

Patients with left main (LM) coronary artery disease (CAD) are at the highest risk of cardiovascular events. We evaluated possible gene polymorphisms of tumor protein 53 ( TP53, rs1042522, p.Arg72Pro) that can differentiate LM-CAD from patients with more peripheral CAD (MP-CAD) and healthy participants (control group) in 520 individuals (LM-CAD, n = 175; MP-CAD, n = 185; and control group, n = 160). Patients with LM-CAD had the lowest Arg/Arg genotype frequency (36.0%) compared with the MP-CAD (57.3%) and control groups (61.9%), P < .001 for both comparisons. Similarly, the Arg allele was more frequent in the control group than in patients with MP-CAD (78.8% vs 73.2%; P = .007) and LM-CAD (78.8% vs 64.0%; P < .001). The Arg/Pro genotype was more frequent in the LM-CAD group compared with the MP-CAD and control groups (56.0, 31.9, and 33.8, respectively, P < .001 for both comparisons). Furthermore, the frequency of Arg/Arg genotypes was the lowest in the LM-CAD group compared with the MP-CAD and control groups. Knowing that TP53 is an antioncogene protein that acts as a tumor suppressor and regulator of apoptosis, the lowest frequency of Arg/Arg genotype observed in these high-risk patients may indicate lower protection from the atherosclerosis process. Replication studies are needed to evaluate this association.


2011 ◽  
Vol 19 (3) ◽  
pp. 412-418 ◽  
Author(s):  
Ephraim B Beck ◽  
Sandra Erbs ◽  
Sven Möbius-Winkler ◽  
Volker Adams ◽  
Felix J Woitek ◽  
...  

Objective: Exercise training partially corrects endothelial dysfunction in patients with coronary artery disease (CAD). Growth factors like vascular endothelial growth factor (VEGF) as well as erythropoietin (EPO) are known to modulate the bioavailability of nitric oxide and, thereby, contribute to the maintenance of a normal vascular tone. The aim of the present study was to determine the impact of 4 weeks of exercise training on circulating growth factors and to elucidate their involvement in the training-induced changes in vasomotion in patients with CAD. Methods and results: A total of 39 patients were enrolled (training group: n = 20; control group: n = 19). At start of study and after 4 weeks, average peak flow velocity (APV) of the left internal mammary artery (LIMA) in response to acetylcholine was measured invasively in the treatment and control groups. Serum concentrations of VEGF and EPO were determined by enzyme-linked immunosorbent assay. After exercise training, LIMA APV in response to acetylcholine was increased by 93% (from 69 ± 17% at start of study to 133 ± 16% at 4 weeks, p < 0.01 vs. start of study and control). At start of study, there was no association between any of the vascular growth factors and endothelial function. However, after exercise training a close correlation was apparent between the acetylcholine-induced change in APV and EPO ( r = 0.69, p < 0.01) and VEGF ( r = 0.76, p < 0.01) serum concentrations. In the control group, these correlations were not evident and there was no change in endothelial function either. Conclusion: Exercise training improves agonist-mediated endothelium-dependent vasodilatation in CAD, partially through a restoration of the endothelial response to EPO and VEGF.


Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 939-944
Author(s):  
Fu-han Gong ◽  
Xiao-qiang Xiao ◽  
Xue-ping Zhang ◽  
Li Long ◽  
Sheng Huang ◽  
...  

AbstractAtherosclerosis and chemokines are strongly related, but the role of the chemokine CXCL17 in atherogenesis is still poorly understood. We aim to investigate the serum CXCL17 levels in different stages of patients with coronary heart disease and explore whether these differences contribute to atherosclerosis. In the current prospective study, we enrolled 48 patients with unstable angina (UA), 51 patients with stable angina (SA) and 41 patients for the control group (CG). All subjects were diagnosed by coronary angiography and Gensini score was used to evaluate the severity of coronary artery disease. The CXCL17 levels were determined using ELISA, while lipid metabolism indicators and high sensitivity C-reactive protein (hs-CRP) were detected by automatic biochemical analyzer. We observed that the unstable angina group had higher CXCL17 levels compared with the stable angina and the control group. The logistic regression analysis showed that CXCL17 was an independent risk factor for unstable angina. Our results showed that CXCL17 was also statistically correlated with hs-CRP, while it was irrelevant with Gensini score. CXCL17 levels were associated with activity of inflammatory response and the instability of atherosclerotic plaques. These results suggest that CXCL17 elevation may be a potential new biomarker of unstable angina.


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