scholarly journals The Effect of Maximal Exercise on Matrix Metalloproteinase, its Inhibitor (MMP9 and TIMP1), and the Role of MMP9 -1562 C/T and TIMP1 372 T/C Polymorphisms

2021 ◽  
Author(s):  
Merve Koca Kosova ◽  
Faruk Turgay ◽  
Oya Yigittürk ◽  
Semih Aşıkovalı ◽  
Sercin Kosova ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Acute Exercise ◽  
Maximal Exercise ◽  
Low Density Lipoprotein ◽  
Venous Blood ◽  
Density Lipoprotein ◽  
Post Exercise ◽  
Sedentary Group ◽  
Before And After

Abstract To investigate the levels of MMP9 and TIMP1 before and after acute maximal exercise and the role of MMP9 -1562 C/T and TIMP1 372 T/C polymorphisms in athletes and sedentary individuals. The athlete group (n = 43) and sedentary group (n = 43) performed the Yo-Yo intermittent recovery test level 1. A blood sample was taken before and after the test. MMP9, TIMP1, MMP9/TIMP1 ratio, blood lipids, and lipoproteins (total cholesterol, high and low-density lipoprotein cholesterol) and indicators of muscle damage (creatine kinase, aspartate aminotransferase, alanine aminotransferase) were determined from postprandial venous blood samples. Genetic polymorphisms were determined from DNA samples obtained from peripheral blood. MMP9 levels were found higher in both groups after the YOYO IR-1 test (exercise) (sedentary group, pre-exercise: 1771.15 ± 862.17 pg/mL, post-exercise: 2172.18 ± 680.93 pg/mL; athletic group, pre-exercise: 1373.57 ± 705.16 pg/mL, post-exercise: 1723.72 ± 733.88 pg/mL, p < 0.05). TIMP1 levels were also found higher in both groups after exercise (sedentary group, pre-exercise: 4.63 ± 3.99 ng/mL, post-exercise: 5.3 ± 3.51 ng/mL; athletic group, pre-exercise: 3.26 ± 2.34 ng/mL, post-exercise: 3.59 ± 1.99 ng/mL, p < 0.05). Basal serum MMP9 levels were significantly higher in sedentary individuals as compared with athletes (p = 0.046). MMP9 -1562 C/T and TIMP1 372 T/C polymorphisms had no effect on MMP9 and TIMP1 levels (p > 0.05). As a conclusion acute exercise increases MMP9 and TIMP1 levels in male athletes and sedentary individuals. Chronic anaerobic exercises performed by the athletic group may caused lower MMP9 levels. MMP9 -1562 C/T and TIMP1 372 T/C genetic polymorphisms are not associated with MMP9 and TIMP1 activation.

Genetic Polymorphisms, LDL-C and sdLDL-C Help Optimize Coronary Heart Disease (CHD) Therapy

2021 ◽  
Author(s):  
Ruozhu Dai ◽  
Huilin Zhuo ◽  
Wei Wang ◽  
Xinjun Wang ◽  
Xiaoyu Zhao
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Genetic Polymorphisms ◽  
Therapy Monitoring ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Healthy People ◽  
Risk Indicator ◽  
Before And After ◽  
A Prospective Study

Abstract Background: Low-density lipoprotein cholesterol (LDL-C) and small, dense LDL-C (sdLDL-C) are important risk indicator of coronary heart disease (CHD), but their application in therapy monitoring of CHD is still far from being elucidated. Following the concept of precision medicine, we investigated whether the scientific medication based on medication-sensitive genes can reverse the LDL-C and sdLDL-C status in human bloodstream, so as to reveal the possibility of them as a monitoring indicator of CHD efficacy.Methods: A prospective study of CHD cohort containing 208 Chinese CHD patients (158 males and 50 females) and 20 healthy people (14 males and 6 females) was recruited. LDL-C and its subfractions were detected before and after treatment. Polymorphism of medication-sensitive genes, including SLCO1B1 (rs4149056, 521T>C), CYP2C19*2 (rs4244285, c.681G>A), and CYP2C19*3 (rs4986893, c.636G>A) were detected for medication guidance.Results: Nearly half of Chinese CHD patients (47.60%, 99/208) had genetic polymorphisms with homozygous or heterozygous mutations within these three genes. LDL-1 and LDL-2, subfractions of LDL-C, had a 100% positive rate in CHD patients and healthy people. However, sdLDL-C components of LDL-5 to LDL-7 were only enrichment in CHD patients. Moreover, the mean amount of sdLDL-C subfractions in CHD patients was significantly higher than that in healthy people. Among 180 patients with treatment remission, 81.67% (n=147) of CHD patients had decreased LDL-C, while 61.67% (n=111) of patients had decreased sdLDL-C.Conclusion: sdLDL-C has better accuracy on CHD screening than LDL-C, while LDL-C was more suitable for CHD therapy monitoring. Combined medication-sensitive genes polymorphism, LDL-C and sdLDL-C detection would optimize the treatment strategy for CHD patients.

The Role of the Low-Density Lipoprotein Receptor-Related Protein (LRP) in the Plasma Clearance and Liver Uptake of Recombinant Single-chain Urokinase-type Plasminogen Activator in Rats

1997 ◽  
Vol 77 (04) ◽  
pp. 710-717 ◽  
Author(s):  
Marieke E van der Kaaden ◽  
Dingeman C Rijken ◽  
J Kar Kruijt ◽  
Theo J C van Berkel ◽  
Johan Kuiper
Keyword(s):  
Plasminogen Activator ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Single Chain ◽  
Liver Uptake ◽  
Type Plasminogen Activator ◽  
Parenchymal Liver ◽  
Urokinase Type Plasminogen Activator ◽  
Density Lipoprotein Receptor

SummaryUrokinase-type plasminogen activator (u-PA) is used as a thrombolytic agent in the treatment of acute myocardial infarction. In vitro, recombinant single-chain u-PA (rscu-PA) expressed in E.coli is recognized by the Low-Density Lipoprotein Receptor-related Protein (LRP) on rat parenchymal liver cells. In this study we investigated the role of LRP in the liver uptake and plasma clearance of rscu-PA in rats. A preinjection of the LRP inhibitor GST-RAP reduced the maximal liver uptake of 125I-rscu-PA at 5 min after injection from 50 to 30% of the injected dose and decreased the clearance of rscu-PA from 2.37 ml/min to 1.58 ml/min. Parenchymal, Kupffer and endothelial cells were responsible for 40, 50 and 10% of the liver uptake, respectively. The reduction in liver uptake of rscu-PA by the preinjection of GST-RAP was caused by a 91 % and 62% reduction in the uptake by parenchymal and Kupffer cells, respectively. In order to investigate the part of rscu-PA that accounted for the interaction with LRP, experiments were performed with a mutant of rscu-PA lacking residues 11-135 (= deltal25- rscu-PA). Deletion of residues 11-135 resulted in a 80% reduction in liver uptake and a 2.4 times slower clearance (0.97 ml/min). The parenchymal, Kupffer and endothelial cells were responsible for respectively 60, 33 and 7% of the liver uptake of 125I-deltal25-rscu-PA. Preinjection of GST-RAP completely reduced the liver uptake of delta 125-rscu-PA and reduced its clearance to 0.79 ml/min. Treatment of isolated Kupffer cells with PI-PLC reduced the binding of rscu-PA by 40%, suggesting the involvement of the urokinase-type Plasminogen Activator Receptor (u-PAR) in the recognition of rscu-PA. Our results demonstrate that in vivo LRP is responsible for more than 90% of the parenchymal liver cell mediated uptake of rscu-PA and for 60% of the Kupffer cell interaction. It is also suggested that u-PAR is involved in the Kupffer cell recognition of rscu-PA.

Melatonin Improves Lipid Profile and Ameliorates Lipid Peroxidation in Patients with Chronic Kidney Disease.

2018 ◽  
pp. 38-45
Keyword(s):  
Lipid Peroxidation ◽  
Placebo Group ◽  
Lipid Profile ◽  
Kidney Diseases ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Before And After ◽  
Inhibit Lipid Peroxidation ◽  
Controlled Clinical Study

Dyslipidemia and oxidative modifications of lipid are frequently associated in patients with chronic kidney diseases (CKD) and considered the most important risk factors for cardiovascular events. Melatonin is a well-known potent antioxidant and has beneficial effect on lipid metabolism. the study was designed to evaluate if Melatonin could improve lipid profile and ameliorates lipid peroxidation. This single blind placebo controlled clinical study carried out on 41 patients with CKD who were randomized into two groups, control groups (n=20) those who received placebo cap and melatonin group those who received 5mg melatonin (n=21). Lipid profile [total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C)] and parameters of lipid peroxidation [oxidized LDL (oxLDL) and malondialdehyde (MDA) were measured before and after 12 weeks of the treatment. After 12 weeks of treatment, melatonin significantly increased HDL-C and decreased LDL-C compared to the initial value. The elevation in HDL-C and reduction in LDL-C were significantly different from that in placebo group. Also, both oxLDL and MDA levels significantly lowered by melatonin compared to the baseline and to the placebo group. Collectively, the results of our study showed that melatonin has advantageous effect on lipid profile and inhibit lipid peroxidation in patients with CKD.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

scholarly journals Genetic variation of RNF145 gene and blood lipid levels in Xinjiang population, China

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jing Ming ◽  
Xian Wei ◽  
Min Han ◽  
Dilare Adi ◽  
Jialin Abuzhalihan ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Ring Finger ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Lipid Profiles ◽  
Cholesterol Levels ◽  
General Linear Model Analysis ◽  
Confounding Variables ◽  
Before And After ◽  
Detection Response

AbstractDyslipidemia is one of the main risk factors for coronary heart disease (CHD). The E3 ubiquitin ligase which is encoded by the ring finger protein 145 (RNF145) gene is very important in the mediation of cholesterol synthesis and effectively treats hypercholesterolemia. Thus, the purpose of the present research is to investigate the connection between the polymorphism of the RNF145 gene and cholesterol levels in the populations in Xinjiang, China. A total of 1396 participants (Male: 628, Female: 768) were included in this study for genetic analysis of RNF145 gene, and we used the modified multiple connection detection response (iMLDR) technology to label two SNPs (rs17056583, rs12188266) of RNF145 genotyping. The relationship between the genotypes and the lipid profiles was analyzed with general linear model analysis after adjusting confounding variables. Through the analysis of the two SNPs in RNF145 gene, we discovered that both rs17056583 and rs12188266 were related to total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations (All P < 0.001). In addition, the association of rs17056583 and rs12188266 with lipid profiles concentrations is still statistically significant after multivariate adjustment of sex, age, smoking, obesity, drinking, diabetes, hypertension and lipid profiles. Meanwhile, we also found that rs17056583 was associated with high triglycerides concentrations before and after adjustment (All P < 0.001). Our study shows that both rs17056583 and rs12188266 SNPs of RNP145 gene are related to TC and LDL-C concentrations in Xinjiang population.

scholarly journals Treatment with Delipid Extracorporeal Lipoprotein Filter from Plasma after Intravenous Thrombolysis for Acute Ischemic Stroke: A Single-Center Experience

2020 ◽  
Vol 10 (3) ◽  
pp. 148-158
Author(s):  
Yu Cui ◽  
Zhong-He Zhou ◽  
Xiao-Wen Hou ◽  
Hui-Sheng Chen
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Intravenous Thrombolysis ◽  
Single Center Experience ◽  
Before And After ◽  
Prospective Trials ◽  
Symptomatic Intracranial Hemorrhage ◽  
Rate Of Improvement

<b><i>Introduction:</i></b> The delipid extracorporeal lipoprotein filter from plasma (DELP) has been approved for the treatment of acute ischemic stroke (AIS) by the China Food and Drug Administration, but its effectiveness and mechanism are not yet fully determined. The purpose of this study was to evaluate the effect of DELP treatment on AIS patients after intravenous thrombolysis. <b><i>Methods:</i></b> A retrospective study was performed on AIS patients with no improvement within 24 h after intravenous thrombolysis who were subsequently treated with or without DELP. Primary outcome was the proportion with a modified Rankin scale (mRS) of 0–1 at 90 days. Secondary outcomes were changes in National Institute of Health Stroke Scale (NIHSS) score from 24 h to 14 days after thrombolysis, and the rate of improvement in stroke-associated pneumonia (SAP). The main safety outcomes were the rates of symptomatic intracranial hemorrhage and mortality. To investigate its mechanisms, serum biomarkers were measured before and after DELP. <b><i>Results:</i></b> A total of 252 patients were recruited, 63 in the DELP group and 189 matched patients in the NO DELP group. Compared with the NO DELP group, the DELP group showed an increase in the proportion of mRS 0–1 at 90 days (<i>p</i> = 0.042). More decrease in NIHSS from 24 h to 14 days (<i>p</i> = 0.024), a higher rate of improvement in SAP (<i>p</i> = 0.022), and lower mortality (<i>p</i> = 0.040) were shown in DELP group. Furthermore, DELP decreased levels of interleukin (IL)-1β, E-selectin, malondialdehyde, matrix metalloprotein 9, total cholesterol, low-density lipoprotein, and fibrinogen, and increased superoxide dismutase (<i>p</i>&#x3c; 0.05). <b><i>Conclusions:</i></b> DELP following intravenous thrombolysis should be safe, and is associated with neurological function improvement, possibly through multiple neuroprotective mechanisms. Prospective trials are needed.

Genetic polymorphisms of low density lipoprotein receptor can modify stroke presentation

2010 ◽  
Vol 32 (5) ◽  
pp. 535-540 ◽  
Author(s):  
Jiann-Der Lee ◽  
Ya-Hui Lin ◽  
Huan-Lin Hsu ◽  
Yen-Chu Huang ◽  
Chih-Ying Wu ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

Drug related metabolites and genetic polymorphisms predict low low-density lipoprotein cholesterol response to atorvastatin treatment in patients with coronary heart disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Munkhaugen ◽  
E Sverre ◽  
O Kristiansen ◽  
M.W Fagerland ◽  
K Peersen ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Genetic Polymorphisms ◽  
Individual Variation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Funding Source ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Atorvastatin Treatment

Abstract Background There is considerable individual variation in the low-density lipoprotein cholesterol (LDL-C) reduction at all classes and doses of statins. Knowledge of the determinants of individual variation LDL-C response upon statin treatment may pave the way for personalized and optimized statin treatment. Purpose We aimed to determine clinical and drug related predictors of variability of LDL-C response to atorvastatin 40 mg in patients with coronary heart disease. Methods This is an explorative study among 70 patients enrolled in the MUscle Side-Effects of atorvastatin in coronary patients (MUSE) randomized double blinded cross-over trial. Absolute and relative changes in LDL-C after 7 weeks treatment with atorvastatin 40 mg/day and 7 weeks treatment with placebo, were calculated for each patient. Linear regression analyses were applied to investigate the association between clinical (10 variables) and drug related (atorvastatin and/or metabolites, 18 variables) predictors and changes in LDL-C. Results Adherence to allocated treatment was high as confirmed by atorvastatin levels in blood and a mean proportion of days covered of 99% (range 91–100%). Mean reduction in LDL-C on atorvastatin treatment (LDL-C atorvastatin – LDL-C placebo) was 2.1 (SD 0.7, range 0.3 to 3.4) mmol/L. Mean percentage reduction in LDL-C was 51.1 (SD 11.2, range 29 to 60)%, and 37 patients (52.9%) had &lt;50% LDL-C reduction. Genetic polymorphisms in SLCO1B1 or CYP3A (B 0.06, 95% CI 0.01 to 0.12, p=0.026), increasing number of coronary events (B 0.06, 95% CI 0.002 to 0.10, p=0.005), increasing trough concentration of 4-OH atorvastatin lactone (B 0.05, 95% CI 0.01 to 0.08, p=0.005) and increasing trough concentration of 4-OH atorvastatin acid (B 0.05, 95% CI 0.01 to 0.08, p=0.006) were the significant determinants of lower relative change (%) in LDL-C, in adjusted analyses. Age, gender, somatic comorbidity, cardiovascular risk factors, statin dependent muscle side-effects and other clinical and drug related determinants were not associated with changes in LDL-C. Conclusions There is considerable inter-individual variation in the LDL-C response upon treatment with atorvastatin despite confirmed high statin adherence. This is the first study reporting that genetic polymorphisms involved in the metabolism of statins and atorvastatin metabolites predict lower LDL-C response. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Association of Health, Grant/Award

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