scholarly journals Aspirin resistance with genetic dyslipidemia: contribution of vascular thromboxane generation

2010 ◽  
Vol 42 (3) ◽  
pp. 331-341 ◽  
Author(s):  
Jefferson C. Frisbee ◽  
Adam G. Goodwill ◽  
Phoebe A. Stapleton ◽  
Stephanie J. Frisbee ◽  
Alexandre C. d'Audiffret
Keyword(s):  
Low Dose ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Clinical Intervention ◽  
Epidemiological Studies ◽  
Aspirin Resistance ◽  
Aspirin Therapy ◽  
Vascular Events ◽  
Beneficial Impact ◽  
The Impact

One clinical intervention against the negative outcomes associated with atherothrombotic vascular disease (AVD) is low-dose, chronic aspirin therapy. However, epidemiological studies suggest that recurrence of adverse vascular events with aspirin therapy is growing and associated with therapy duration. The contributors to this outcome are unclear and include poor patient compliance and aspirin-resistant platelet thromboxane A2 (TxA2) production. Based on previous results in hypercholesterolemic mice, we hypothesized that elevated aspirin-insensitive arachidonic acid (AA)-induced TxA2 production by the vascular endothelium contributes to aspirin resistance in AVD independent of platelet behavior. AA-induced dilation was blunted in aortic rings and in arterioles from apolipoprotein E (ApoE) and low-density lipoprotein receptor (LDLR) gene deletion mice (vs. C57/Bl6/J), partially due to elevated TxA2 production. Acute inhibition of cyclooxygenases or TxA2 synthase attenuated the increased TxA2 production in ApoE and LDLR and improved AA-induced dilation, responses that were mirrored by chronic treatment with low-dose aspirin of 16 wk duration. However, this effect was not temporally stable, and, with longer-duration therapy, the beneficial impact of aspirin on outcomes diminished. A similar, though less robust, pattern to the impact of chronic aspirin therapy on vascular outcomes was identified with chronic antioxidant treatment (TEMPOL). These results suggest that in dyslipidemic mice, the beneficial impact of chronic aspirin therapy on improving vascular outcomes decay with time and that a contributing element to subsequent negative vascular events may be the development of aspirin-resistant TxA2 production by the vasculature itself.

Pandora's Box: mitochondrial defects in ischaemic heart disease and stroke

2017 ◽  
Vol 19 ◽  
Author(s):  
Sasan Andalib ◽  
Afshin A. Divani ◽  
Tanja M. Michel ◽  
Poul F. Høilund-Carlsen ◽  
Manouchehr S. Vafaee ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischaemic Heart Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Causative Role ◽  
Vascular Events ◽  
Molecular Events ◽  
Oxidised Low Density Lipoprotein ◽  
The Impact

Ischaemic heart disease and stroke are vascular events with serious health consequences worldwide. Recent genetic and epigenetic techniques have revealed many genetic determinants of these vascular events and simplified the approaches to research focused on ischaemic heart disease and stroke. The pathogenetic mechanisms of ischaemic heart disease and stroke are complex, with mitochondrial involvement (partially or entirely) recently gaining substantial support. Not only can mitochondrial reactive oxygen species give rise to ischaemic heart disease and stroke by production of oxidised low-density lipoprotein and induction of apoptosis, but the impact on pericytes contributes directly to the pathogenesis. Over the past two decades, publications implicate the causative role of nuclear genes in the development of ischaemic heart disease and stroke, in contrast to the potential role of mitochondrial DNA (mtDNA) in the pathophysiology of the disorders, which is much less understood, although recent studies do demonstrate that the involvement of mitochondria and mtDNA in the development of ischaemic heart disease and stroke is likely to be larger than originally thought, with the novel discovery of links among mitochondria, mtDNA and vascular events. Here we explore the molecular events and mtDNA alterations in relation to the role of mitochondria in ischaemic heart disease and stroke.

scholarly journals Monitoring of Aspirin Therapy in Patients with Cerebrovascular Pathology

2021 ◽  
Vol 17 (4) ◽  
pp. 537-543
Author(s):  
M. M. Tanashyan ◽  
A. A. Raskurazhev ◽  
A. A. Kornilova ◽  
A. A. Shabalina ◽  
D. A. Abaimov ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Aspirin Resistance ◽  
Small Subunit ◽  
Aspirin Therapy ◽  
Therapeutic Drug ◽  
Laboratory Assessment

Aim. Evaluation of various methods for determining the effectiveness of aspirin therapy and aspirin resistance in patients with cerebrovascular disease (CVD) depending on the presence of type 2 diabetes mellitus (T2DM).Materials and methods. The prospective study included 78 patients with various manifestations of CVD. All patients received acetylsalicylic acid (ASA) 75 mg daily. Along with a comprehensive clinical examination, a laboratory assessment of platelet function with the usage of Born method with aggregometer, a detailed biochemical blood test (including the determination of the small subunit of low density lipoprotein [s-LDL]), as well as therapeutic drug monitoring of salicylates were performed on a gas chromatograph-mass spectrometer.Results. In 53% of cases, the absence or insufficiency of the effect of ASA on platelet aggregation was noted. Two subgroups were separately identified: with T2DM; (n=40) and without T2DM (n=38). Insufficient effect of the drug on platelet aggregation characteristics were observed in 65% of patients with T2DM and in 38% without T2DM. The differences were revealed between the groups in triglycerides, s-LDL, glycemic and glycated hemoglobin (p <0.05). In the group of patients with T2DM, the median ASA concentration was 0.01 [0; 0.32] μg/ml, and salicylic acid (SA)– 0.20 [0; 0.39] μg/ml, while in patients without T2DM higher values were noted: ASA 0.29 [0.15; 0.55] μg/ml, SA – 0.33 [0.05; 0.73] μg/ml. A decrease in the concentration of ASA was associated with an increase in the level of ADP-induced platelet aggregation. There was an increase in the levels of ADPand adrenaline-induced platelet aggregation with a decrease in the concentration of ASA (p=0.004) and SA (p=0.006). Therapeutic drug monitoring revealed a more significant decrease in ASA level in T2DM than in the comparison group (p=0.025).Conclusion. It is advisable to monitor aspirin therapy both with the assessment of platelet aggregation and with therapeutic drug monitoring. The relationship between the level of ASA and SA in the blood plasma and the functional activity of platelets was confirmed. The presence of T2DM is associated with a decrease in the concentration of ASA and aspirin resistance detected in therapeutic drug monitoring.

scholarly journals Psoriasis and Cardiovascular Risk—Do Promising New Biomarkers Have Clinical Impact?

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Sirje Kaur ◽  
Külli Kingo ◽  
Mihkel Zilmer
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Epidemiological Studies ◽  
Overweight And Obesity ◽  
Biologically Active ◽  
Cvd Risk ◽  
Low Hdl ◽  
New Biomarkers ◽  
The Impact

Epidemiological studies suggest an increased prevalence of cardiovascular disease (CVD) in patients with psoriasis (PS). Therefore, emphasis has lately been laid on the necessity for clinical evaluation of the risk of CVD in these patients. The systemic inflammatory markers C-reactive protein (CRP) and interleukin- (IL-) 6, which have long been used to predict future CVD in the general population, are increased manyfold in patients with PS. Lipid abnormalities characterized by elevated triglycerides, low HDL cholesterol, and higher concentrations of LDL cholesterol and its oxidized form are also prevalent in patients. There is a need for additional laboratory markers for the assessment of cardiovascular status of patients with PS. Due to frequent comorbid overweight and obesity, biologically active compounds produced by adipocytes may have an impact on monitoring the status of the cardiovascular system of patients with PS. For this purpose, two adipokines, adiponectin and leptin, have been most extensively studied. The review focuses on some inflammatory and oxidative stress aspects in patients with PS through the analysis of the impact of prominent adipokines and oxidized low-density lipoprotein (oxLDL) to assess their eligibility for clinical practice as markers of CVD risk in patients with PS.

Epidemiology Of Myocardial Infarction: Magnitude Of The Problem, Cause And Risk Factors

1981 ◽  
Author(s):  
W B Kannel
Keyword(s):  
Risk Factors ◽  
Risk Evaluation ◽  
Death Rate ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Joint Effect ◽  
Low Density Lipoprotein Cholesterol ◽  
The Impact ◽  
Marginal Risk

Coronary heart disease is a common, highly lethal, disease which frequently attacks without warning and too often presents with sudden death as the first symptom. Chances of an American male developing CHD before age 60 are one in five.Most angina, infarctions and sudden deaths represent medical failures which should have been forecasted and prevented. About 30% of first MI's will shortly develop angina and experience a per annum death rate, half of which will be sudden deaths. Reinfarctions will occur at 6% per year and half the recurrences will be fatal.No major innovations are needed to identify coronary candidates or to establish their risk from the joint effect of known risk factors. However, all have much to learn about motivating changes in behavior required to control the major risk factors such as cigarette smoking, faulty diet, overweight, sedentary living, abnormal lipids, hypertension and impaired glucose tolerance.Low density lipoprotein cholesterol promotes atherogenesis whereas HDL-cholesterol is protective, and the net effect is judged by their ratio. Hypertension, systolic or diastolic, labile or fixed, at any age in either sex is a powerful contributor to CHD. The impact of diabetes is greater for women, diminishes with age and varies depending on coexisting risk factors.Optimal risk evaluation requires quantitative combination of risk factors so as to include persons with multiple marginal risk factor abnormalities who are at high risk.

scholarly journals A Comparison of Lipid Profile Between Sedentary and Non Sedentary Workers

1970 ◽  
Vol 22 (1) ◽  
pp. 10-14
Author(s):  
Iftekhar Mahmood ◽  
MM Rahman Khan ◽  
M Khalilur Rahman ◽  
MM Hoque Chowdhury
Keyword(s):  
Cardiovascular Disease ◽  
Life Style ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
Control Group ◽  
Age Group ◽  
Sedentary Life ◽  
Bank Employees ◽  
Sedentary Life Style

In different epidemiological studies, an association between sedentary life style and incidence of cardiovascular diseases has been demonstrated. Dyslipidaemia is one of the important risk factors of cardiovascular disease. An association of dyslipidaemia with sedentary life style has been considered. This study was carried out among 50 sedentary workers (teachers, office staffs, bank employees) at Pabna District and 50 individuals with non-sedentary jobs matched for age group and sex for the control group to see the association. Body mass index (BMI), blood pressure (BP), plasma level of glucose, total cholesterol, low density lipoprotein (LDL), and triglycerides (Tgs) were found to be significantly higher whereas high density lipoprotein (HDL) was found to be significantly lower among the sedentary workers as compared with the control subjects. From the study, it appears that dyslipidaemia is more common in sedentary workers and the relative risk for cardiovascular disease is increased among them due to the sedentary nature of their jobs. DOI: 10.3329/taj.v22i1.5014 TAJ 2009; 22(1): 10-14

scholarly journals Identification of 31 novel mutations in the F8 gene in Spanish hemophilia A patients: structural analysis of 20 missense mutations suggests new intermolecular binding sites

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3468-3478 ◽  
Author(s):  
Adoración Venceslá ◽  
María Ángeles Corral-Rodríguez ◽  
Manel Baena ◽  
Mónica Cornet ◽  
Montserrat Domènech ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Missense Mutations ◽  
Factor X ◽  
Novel Mutations ◽  
Large Deletions ◽  
Function Relationship ◽  
The Impact

Abstract Hemophilia A (HA) is an X-linked bleeding disorder caused by a wide variety of mutations in the factor 8 (F8) gene, leading to absent or deficient factor VIII (FVIII). We analyzed the F8 gene of 267 unrelated Spanish patients with HA. After excluding patients with the common intron-1 and intron-22 inversions and large deletions, we detected 137 individuals with small mutations, 31 of which had not been reported previously. Eleven of these were nonsense, frameshift, and splicing mutations, whereas 20 were missense changes. We assessed the impact of the 20 substitutions based on currently available information about FV and FVIII structure and function relationship, including previously reported results of replacements at these and topologically equivalent positions. Although most changes are likely to cause gross structural perturbations and concomitant cofactor instability, p.Ala375Ser is predicted to affect cofactor activation. Finally, 3 further mutations (p.Pro64Arg, p.Gly494Val, and p.Asp2267Gly) appear to affect cofactor interactions with its carrier protein, von Willebrand factor, with the scavenger receptor low-density lipoprotein receptor–related protein (LRP), and/or with the substrate of the FVIIIapi•FIXa (Xase) complex, factor X. Characterization of these novel mutations is important for adequate genetic counseling in HA families, but also contributes to a better understanding of FVIII structure-function relationship.

Abstract 3691: Deletion of Suppressor Of Cytokine Signaling-1 in a Murine Model of Atherosclerosis Results in a Lethal Systemic Inflammation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Christina Grothusen ◽  
Harald Schuett ◽  
Stefan Lumpe ◽  
Andre Bleich ◽  
Silke Glage ◽  
...  
Keyword(s):  
Foam Cell ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
The Impact

Introduction: Atherosclerosis is a chronic inflammatory disease of the cardiovascular system which may result in myocardial infarction and sudden cardiac death. While the role of pro-inflammatory signaling pathways in atherogenesis has been well characterized, the impact of their negative regulators, e.g. suppressor of cytokine signaling (SOCS)-1 remains to be elucidated. Deficiency of SOCS-1 leads to death 3 weeks post-partum due to an overwhelming inflammation caused by an uncontrolled signalling of interferon-gamma (IFNγ). This phenotype can be rescued by generating recombination activating gene (rag)-2, SOCS-1 double knock out (KO) mice lacking mature lymphocytes, the major source of IFNγ. Since the role of SOCS-1 during atherogenesis is unknown, we investigated the impact of a systemic SOCS-1 deficiency in the low-density lipoprotein receptor (ldlr) KO model of atherosclerosis. Material and Methods: socs-1 −/− /rag-2 −/− deficient mice were crossed with ldlr-KO animals. Mice were kept under sterile conditions on a normal chow diet. For in-vitro analyses, murine socs-1 −/− macrophages were stimulated with native low density lipoprotein (nLDL) or oxidized (ox)LDL. SOCS-1 expression was determined by quantitative PCR and western blot. Foam cell formation was determined by Oil red O staining. Results: socs-1 −/− /rag-2 −/− /ldlr −/− mice were born according to mendelian law. Tripel-KO mice showed a reduced weight and size, were more sensitive to bacterial infections and died within 120 days (N=17). Histological analyses revealed a systemic, necrotic, inflammation in Tripel-KO mice. All other genotypes developed no phenotype. In-vitro observations revealed that SOCS-1 mRNA and protein is upregulated in response to stimulation with oxLDL but not with nLDL. Foam cell formation of socs-1 −/− macrophages was increased compared to controls. Conclusion: SOCS-1 seemingly controls critical steps of atherogenesis by modulating foam cell formation in response to stimulation with oxLDL. SOCS-1 deficiency in the ldlr-KO mouse leads to a lethal inflammation. These observations suggest a critical role for SOCS-1 in the regulation of early inflammatory responses in atherogenesis.

scholarly journals Liver X Receptor Nuclear Receptors Are Transcriptional Regulators of Dendritic Cell Chemotaxis

2018 ◽  
Vol 38 (10) ◽  
Author(s):  
Susana Beceiro ◽  
Attila Pap ◽  
Zsolt Czimmerer ◽  
Tamer Sallam ◽  
Jose A. Guillén ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Low Density Lipoprotein ◽  
Myeloid Cells ◽  
Density Lipoprotein ◽  
Loss Of Function ◽  
Transcriptional Responses ◽  
Cd38 Expression ◽  
The Impact

ABSTRACTThe liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DCs), are still poorly understood. Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs. Our results identified an LXR-dependent pathway that is important for DC chemotaxis. LXR-deficient mature DCs are defective in stimulus-induced migrationin vitroandin vivo. Mechanistically, we show that LXRs facilitate DC chemotactic signaling by regulating the expression of CD38, an ectoenzyme important for leukocyte trafficking. Pharmacological or genetic inactivation of CD38 activity abolished the LXR-dependent induction of DC chemotaxis. Using the low-density lipoprotein receptor-deficient (LDLR−/−) LDLR−/−mouse model of atherosclerosis, we also demonstrated that hematopoietic CD38 expression is important for the accumulation of lipid-laden myeloid cells in lesions, suggesting that CD38 is a key factor in leukocyte migration during atherogenesis. Collectively, our results demonstrate that LXRs are required for the efficient emigration of DCs in response to chemotactic signals during inflammation.

scholarly journals Evaluation of hydrated extract of phaseolus Vulgaris L. (bean plant) on hypoglycemia and hypolipidemic in streptozotocin-induced diabetic albino Wistar rats

2019 ◽  
Vol 10 (4) ◽  
pp. 3704-3710
Author(s):  
Helisha Ruth Obonyo ◽  
Senthemarai Selvi V
Keyword(s):  
Phaseolus Vulgaris ◽  
Blood Serum ◽  
Common Bean ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
Low Density ◽  
Phaseolus Vulgaris L ◽  
Reference Drug ◽  
The Impact

The current research was intended to comprehend hypoglycemic and anti-lipidaemic exercises of hydrated common bean (phaseolus Vulgaris L.) seed extracts on streptozotocin-induced diabetic albino rats. At a set portion fluctuate of 100, 200,300 mg/kg body weight of common bean extracts was orally directed as one portion for every day to polygenic disorder rats for a measure of thirty days. The impact of P.vulgaris L. on hypoglycemic, glycosylated hemoprotein (HbA1c) and blood serum lipid profile (Total cholesterin), Triglyceride (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), High-density lipoprotein (HDL)) in plasma were estimated in the regular and diabetic induced rat. The outcomes demonstrated that quick glucose,serum TC, TG, LDL, VLDL, levels were significantly (p<0.05) attenuate, while blood serum HDL, the level was extensively (p<0.05) upgraded inside the diabetic rats. The inconclusive amount of pace of 300 mg/kg is more reasonable than that of a hundred mg/kg. Our examination so shows that Phaseolus vulgaris L has a powerful adversary to diabetic and anti-lipidaemic impacts on streptozotocin-induced diabetic rats, and results were comparable to reference drug glibenclamide.

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