RESUMO
Atherosclerotic plaque instability increases the risk of stroke. As such, determining the nature of an instability atherosclerotic plaque may speed up qualification for carotid endarterectomy (CEA), thus reducing the risk of acute vascular events. The aim of the study was to determine the diagnostic value of oxidized LDL cholesterol (ox-LDL), matrix metalloproteinase 9 (MMP-9) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in serum as a prognostic markers of instability atherosclerotic plaques. Serum was collected from 67 patients who underwent CEA in accordance with the qualification criteria. The levels of ox-LDL, MMP-9 and 8-OHdG were assessed by ELISA. The predictive value of the markers was determined based on an ROC curve, and the cut-off points with the highest sensitivity and specificity were determined. Patients with unstable atherosclerotic plaque had significantly higher serum ox-LDL, MMP-9 and 8-OHdG values. It was found that in patients before CEA, ox-LDL >31.4 ng/mL was associated with an 82.5% probability of unstable atherosclerotic plaque, MMP-9 >113.1 ng/mL with 78.6%, and 8-OHdG >2.15 ng/mL with 64.7%. Multivariate regression analysis found ox-LDL to be an independent factor associated with plaque instability. Patients with unstable plaques tend to have higher serum levels of ox-LDL, MMP-9 and 8-OHdG compared to those with stable plaques. The optimal cut-off point for ox-LDL (AUC 0.86, p <0.0001) was 31.14 ng/mL, with 91.18% sensitivity and 78.79% specificity. The high sensitivity and specificity of ox-LDL suggests that it can be used as an independent marker of plaque instability.
Assuntos
Biomarcadores , Endarterectomia das Carótidas , Lipoproteínas LDL , Metaloproteinase 9 da Matriz , Placa Aterosclerótica , Humanos , Lipoproteínas LDL/sangue , Placa Aterosclerótica/cirurgia , Placa Aterosclerótica/sangue , Placa Aterosclerótica/patologia , Masculino , Feminino , Biomarcadores/sangue , Prognóstico , Metaloproteinase 9 da Matriz/sangue , Idoso , Pessoa de Meia-Idade , Curva ROC , 8-Hidroxi-2'-Desoxiguanosina/sangueRESUMO
SARS-CoV-2 has become one of the most important and challenging medical research topics in recent years. The presence of endothelial dysfunction, immune thrombosis, and oxidative stress contributes to complications and requires more extended hospitalisation of patients. In this article, we focused on analysing the impact of oxidative stress on the severity of COVID-19 infection. The study group consisted of 72 patients with laboratory-confirmed SARS-CoV enrolled. The patients were divided into moderate and severe diseases according to the SCRI (Simple Covid Risk Index, including lymphocyte/D-dimer ratio). Using the ELISA kit, we determined the level of AOPP and 8-OHdG. Patients with severe COVID-19 had higher levels of both AOPP (P < 0.05) and 8-OHdG (P < 0.05) compared to patients with moderate disease. Albumin levels were significantly lower (P < 0.001), although fibrinogen (P < 0.01), D-dimer (P < 0.001), and TF (P < 0.05) levels were higher in severe patients than in moderate course. AOPP/Alb was also higher among severe patients (P < 0.05). Our data suggest a potential role for AOPP and 8-OHdG in predicting the outcome of SARS-CoV-2 patients. Elevated AOPP levels were associated with increased Dimer-D, TF, and vWF activity levels.
Assuntos
Produtos da Oxidação Avançada de Proteínas , COVID-19 , Humanos , 8-Hidroxi-2'-Desoxiguanosina , SARS-CoV-2 , Estresse OxidativoRESUMO
SGLT2 (Sodium-glucose Cotransporter-2) inhibitors are newer glucose-lowering drugs with many cardiovascular benefits that are not fully understood yet. Endothelial integrity plays a key role in cardiovascular homeostasis. 25-hydroxycholesterol (25-OHC), which is a proatherogenic stimuli that impairs endothelial barrier functions. VE-cadherin is an endothelial-specific protein crucial in maintaining endothelial integrity. The aim of this study was to assess the influence of SGLT2i on the integrity of endothelial cells interrupted by 25-OHC. We also aimed to evaluate whether this effect is associated with changes in the levels of VE-cadherin. We pre-incubated HUVECs with 10 µg/mL of 25-hydroxycholesterol (25-OHC) for 4 h and then removed it and incubated endothelial cells with 1 µM of empagliflozin, 1 µM canagliflozin, or 1 µM dapagliflozin for 24 h. The control group included HUVECs cultured with the medium or with 25-OHC 10 µg/mL. The integrity of endothelial cells was measured by the RTCA-DP xCELLigence system, and VE-cadherin was assessed in confocal microscopy. Our results show that SGLT2 inhibitors significantly increase endothelial integrity in comparison to medium controls, and they improve endothelial cell integrity interrupted by 25-OHC. This effect is associated with significant improvements in VE-cadherin levels. SGLT2i: empagliflozin, canagliflozin, and dapagliflozin have a beneficial effect on the endothelial cell integrity and VE-cadherin levels reduced by 25-OHC.
Assuntos
Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Compostos Benzidrílicos/farmacologia , Canagliflozina/farmacologia , Células Endoteliais , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Células Endoteliais da Veia Umbilical HumanaRESUMO
OBJECTIVE: The prevalence of euthyroid sick syndrome (ESS) and its association with the prognosis of COVID-19 and mortality in patients with lung involvement in COVID-19 have not yet been elucidated. METHODS: Clinical and laboratory data of patients with COVID-19 with or without ESS were collected retrospectively and analyzed on admission. All subjects were admitted to the Department of Internal Diseases and Clinical Pharmacology at Bieganski Hospital between December 2020 and April 2021. RESULTS: In total, 310 medical records of patients with COVID-19 were analyzed retrospectively. Among 215 enrolled patients, 82 cases of ESS were diagnosed. The patients with ESS had higher pro-inflammatory factor levels, longer hospitalizations, and a higher risk of requiring high-flow nasal oxygen therapy or intubation than the patients without ESS. The Kaplan-Meier curve indicated that the patients with ESS had a lower probability of survival when computed tomography showed ≤50% parenchymal involvement compared with that in patients without ESS. However, no differences in mortality were noted in those with more than 50% parenchymal involvement. The survival curve showed that ESS was associated with a higher risk of mortality during hospitalization. CONCLUSION: ESS is closely associated with a poor prognosis, including longer hospitalizations, more frequent intubation, transfer to the intensive care unit, and a higher mortality rate in patients with COVID-19. ESS is a potential prognostic predictor of survival, regardless of lung involvement in COVID-19.
Assuntos
COVID-19 , Síndromes do Eutireóideo Doente , COVID-19/complicações , Síndromes do Eutireóideo Doente/complicações , Síndromes do Eutireóideo Doente/epidemiologia , Hospitalização , Humanos , Prognóstico , Estudos RetrospectivosRESUMO
Atherosclerosis is associated with a haemostatic imbalance characterized by excessive activation of pro-inflammatory and pro-coagulant pathways. Non-vitamin K antagonists oral anticoagulant (NOACs) may reduce the incidence of cardiovascular events, cerebral ischemia, thromboembolic events and atherosclerosis. Chronic inflammation, vascular proliferation and the development of atherosclerosis is also influenced by 25-hydroxycholesterol (25-OHC). The aim of the study was to assess the effect of rivaroxaban and dabigatran on the messenger RNA (mRNA) expression of anti-inflammatory cytokines transforming growth factor ß (TGF-ß), interleukin (IL)-37, IL-35 as well as of pro-inflammatory cytokines IL-18 and IL-23, in endothelial cells damaged by 25-OHC. Human umbilical vascular endothelial cells (HUVECs) were treated with 25-OHC (10 µg/mL), rivaroxaban (100, 500 ng/mL), dabigatran (100, 500 ng/mL), 25-OHC + rivaroxaban, and 25-OHC + dabigatran. The mRNA expression of TGF-ß, IL-37, IL-35 subunits EBI3 and p35, IL-18, and IL-23 was analysed using real-time polymerase chain reaction (PCR). The results showed that 25-OHC decreased TGF-ß and IL-37 mRNA expression and increased EBI3, p35, IL-18, IL-23 mRNA expression in endothelial cell as compared to an untreated control (P < .05). Messenger RNA expression of TGF-ß and IL-37 significantly increased following stimulation with rivaroxaban and dabigatran as compared to an untreated control (P < .01). In HUVECs pre-treated with oxysterol, rivaroxaban and dabigatran increased mRNA expression of TGF-ß, IL-37 and decreased mRNA expression of EBI3, p35, IL-23 and IL-18 as compared to 25-OHC (P < .01). Our finding suggests that both rivaroxaban and dabigatran inhibit the inflammatory activation caused by oxysterol in vitro.
Assuntos
Aterosclerose , Citocinas , Dabigatrana , Células Endoteliais da Veia Umbilical Humana , Hidroxicolesteróis , Rivaroxabana , Administração Oral , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Aterosclerose/imunologia , Fibrilação Atrial/tratamento farmacológico , Citocinas/genética , Citocinas/imunologia , Dabigatrana/farmacologia , Dabigatrana/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/imunologia , Humanos , Hidroxicolesteróis/administração & dosagem , Hidroxicolesteróis/efeitos adversos , Hidroxicolesteróis/farmacologia , Interleucina-18/genética , Interleucina-18/imunologia , Interleucina-23/genética , Interleucina-23/imunologia , Oxisteróis/administração & dosagem , Oxisteróis/efeitos adversos , Oxisteróis/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/imunologiaRESUMO
The virus responsible for the current COVID-19 pandemic is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a new virus with high infectivity and moderate mortality. The major clinical manifestation of COVID-19 is interstitial pneumonia, which may progress to acute respiratory distress syndrome (ARDS). However, the disease causes a potent systemic hyperin-flammatory response, i.e., a cytokine storm or macrophage activation syndrome (MAS), which is associated with thrombotic complications. The complexity of the disease requires appropriate intensive treatment. One of promising treatment is statin administration, these being 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that exert pleiotropic anti-inflammatory effects. Recent studies indicate that statin therapy is associated with decreased mortality in COVID-19, which may be caused by direct and indirect mechanisms. According to literature data, statins can limit SARS-CoV-2 cell entry and replication by inhibiting the main protease (Mpro) and RNA-dependent RNA polymerase (RdRp). The cytokine storm can be ameliorated by lowering serum IL-6 levels; this can be achieved by inhibiting Toll-like receptor 4 (TLR4) and modulating macrophage activity. Statins can also reduce the complications of COVID-19, such as thrombosis and pulmonary fibrosis, by reducing serum PAI-1 levels, attenuating TGF-ß and VEGF in lung tissue, and improving endothelial function. Despite these benefits, statin therapy may have side effects that should be considered, such as elevated creatinine kinase (CK), liver enzyme and serum glucose levels, which are already elevated in severe COVID-19 infection. The present study analyzes the latest findings regarding the benefits and limitations of statin therapy in patients with COVID-19.
Assuntos
Tratamento Farmacológico da COVID-19 , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Animais , COVID-19/complicações , Endotélio/efeitos dos fármacos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inflamação/complicações , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Fibrose Pulmonar/complicações , Fibrose Pulmonar/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Trombose/complicações , Trombose/tratamento farmacológicoRESUMO
Patients with diabetes are at higher risk of cardiovascular diseases and cognitive impairment. SGLT2 inhibitors (Empagliflozin, Canagliflozin, Dapagliflozin, Ertugliflozin, Sotagliflozin) are newer hypoglycemic agents with many pleiotropic effects. In this review, we discuss their neuroprotective potential. SGLT2 inhibitors (SGLT2i) are lipid-soluble and reach the brain/serum ratio from 0.3 to 0.5. SGLT receptors are present in the central nervous system (CNS). Flozins are not fully SGLT2-selective and have an affinity for the SGLT1 receptor, which is associated with protection against ischemia/reperfusion brain damage. SGLT2i show an anti-inflammatory and anti-atherosclerotic effect, including reduction of proinflammatory cytokines, M2 macrophage polarization, JAK2/STAT1 and NLRP3 inflammasome inhibition, as well as cIMT regression. They also mitigate oxidative stress. SGLT2i improve endothelial function, prevent remodeling and exert a protective effect on the neurovascular unit, blood-brain barrier, pericytes, astrocytes, microglia, and oligodendrocytes. Flozins are also able to inhibit AChE, which contributes to cognitive improvement. Empagliflozin significantly increases the level of cerebral BDNF, which modulates neurotransmission and ensures growth, survival, and plasticity of neurons. Moreover, they may be able to restore the circadian rhythm of mTOR activation, which is quite a novel finding in the field of research on metabolic diseases and cognitive impairment. SGLT2i have a great potential to protect against atherosclerosis and cognitive impairment in patients with type 2 diabetes mellitus.
Assuntos
Hipoglicemiantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
BACKGROUND: Atherosclerotic plaques are unstable, and their release may result in thrombosis; therefore, currently, antiplatelet therapy with anticoagulants is recommended for the treatment of acute coronary syndrome. The aim of this study was to assess the effect of oxidized cholesterol on human umbilical vascular endothelial cells (HUVECs). The study also examines the protective and repairing effect of dabigatran and rivaroxaban in a model of vascular endothelial damage with 25-hydroxycholesterol (25-OHC). METHODS: HUVECs were treated with compounds induce DNA single-strand breaks (SSBs) using the comet assay. Oxidative DNA damage was detected using endonuclease III (Nth) or human 8 oxoguanine DNA glycosylase (hOOG1). Reactive oxygen species (ROS) formation was determined using flow cytometry. RESULTS: 25-hydroxycholesterol caused DNA SSBs, induced oxidative damage and increased ROS in the HUVECs; ROS level was lowered by dabigatran and rivaroxaban. Only dabigatran was able to completely repair the DNA SSBs induced by oxysterol. Dabigatran was able to reduce the level of oxidative damage of pyrimidines induced by oxysterol to the level of control cells. CONCLUSIONS: Observed changes strongly suggest that the tested anticoagulants induced indirect repair of DNA by inhibiting ROS production. Furthermore, dabigatran appears to have a higher antioxidant activity than rivaroxaban.
Assuntos
Anticoagulantes/farmacologia , Antioxidantes/farmacologia , Dano ao DNA , Dabigatrana/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Rivaroxabana/farmacologia , Colesterol/análogos & derivados , Colesterol/toxicidade , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Estresse OxidativoRESUMO
The imbalance of anti-inflammatory /pro- inflammatory cytokines plays an important role in the progression of atherosclerosis. Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBVinduced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immunesuppressive cytokine mainly produced by regulatory T cells. Accumulating evidence suggests that IL-35 may represent a target for antiatherosclerotic therapy based on its several anti-inflammatory features. This review provide a brief overview of IL-35 biology and the role of IL-35 in the atherosclerosis, autoimmune disease and cancers.
Assuntos
Aterosclerose/etiologia , Interleucinas/imunologia , Animais , Aterosclerose/imunologia , Aterosclerose/metabolismo , HumanosRESUMO
BACKGROUND: Human vascular endothelial function and integrity may be regulated by many non-specific factors. However, the potential influence of specific antigens via an IgE-mediated mechanism remains unknown. The aim of the study was to determine the expression of the IgE receptors FcεRI and FcεRII in the human vascular endothelium and to assess their relevance in the IgE-mediated regulation of endothelial integrity. MATERIAL/METHODS: FcεRI and FcεRII expression in human umbilical vein endothelial cells (HUVEC) was genetically assessed by PCR with respective primers and sequencing. HUVEC were cultured with IL-4, and changes in FcεRI and FcεRII mRNA expression were analyzed by real-time PCR. Changes in the integrity of endothelium pre-treated with anti-BSA-DNP IgE following exposure to the specific BSA-DNP antigen was assessed using the Real-time Cell Electric Impedance Sensing system (RTCA-DP). RESULTS: PCR and sequencing revealed the expression of FcεRI and FcεRII receptors in the human vascular endothelium. IL-4 caused respective 2- and 3-fold increases in FcεRI and FcεRII mRNA expression. Exposure of endothelium pre-treated with anti-BSA-DNP IgE to specific BSA-DNP antigen led to a 20% increase of endothelial integrity (p<0.05) after 24 hours, but only in cells pre-incubated with IL-4. CONCLUSIONS: The presence of FcεRI and FcεRII may allow the human vascular endothelium to respond to a specific antigen by increasing its integrity via an IgE-mediated mechanism.
Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Imunoglobulina E/imunologia , Receptores de IgE/imunologia , Células Cultivadas , Humanos , Interleucina-4/imunologiaRESUMO
Atrial fibrillation (AF) and obesity is a growing problem of public health both in Poland and in the whole world. AF risk factors may be summarized as elderliness, male sex, smoking, hypertension, diabetes, obesity, coronary heart disease, heart failure, valvular heart disease, cardiac surgery. Once obesity is an independent, potentially modifiable risk factor for AF. The connection between obesity and atrial fibrillation is very up-to-date because of incremental prevalence, almost epidemic of obesity in the whole world. The probability of AF among obese patients increases with concomitant obstructive sleep apnea. Regardless many researches it hasn't been assessed yet how obesity itself predisposes to AF. It could be an effect of change in the atrial anatomy, the rise of atrial pressure, mechanical stretch, interstitial atrial fibrosis and disruption of atrial electric integrity. A great role is ascribed to inflammation, especially proinflammatory cytokines increased by adipocites of left atrial epicardial adiposity.
Assuntos
Fibrilação Atrial/etiologia , Obesidade/complicações , Fibrilação Atrial/epidemiologia , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Polônia/epidemiologia , Prevalência , Fatores de RiscoRESUMO
UNLABELLED: More than 185 million people around the world have been infected with the hepatitis C virus (HCV), of whom 350 000 die each year. HCV is a now a curable disease, and advances in HCV therapy have resulted in steadily higher cure rates. Therapies based on PegINF are still treatment of choice. However PegINF can induce severe adverse events including cardiovascular disease. CASE REPORT: Here we report a 55 year old female patient with the severe hepatitis C and genotype 3 presented with recurring episodes of the loss of consciousness and palpitations in the course of therapy, combining interferon PegINF with ribavirin. During the diagnostics performed the occurrence of non-sustained ventricular. There were no other causes of arrhythmias, such as coronary heart disease or heart failure. It is considered that this is a result of treatment. Because of the confirmed viral clearance completed PegINF therapy at a lower dose, without further complications. CONCLUSIONS: The presented case of our patient illustrates very well the level of difficulty of the taken decisions, especially when treatment complications occurred, while also confirming the fairly assistive and supportive role of the non-invasive methods of cardiovascular diagnostics.
Assuntos
Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Ribavirina/efeitos adversos , Taquicardia Ventricular/induzido quimicamente , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/uso terapêutico , Pessoa de Meia-Idade , Ribavirina/uso terapêuticoRESUMO
PURPOSE: Aronia melanocarpa has an extremely high content of procyanidins and anthocyanins. The multidirectional benefits of consumption of these berries are widely reported. Although numerous studies confirmed the influence of polyphenols on various stages of hemostasis, the exact mechanism of this phenomenon is not understood. The aim of our study was to evaluate the in vitro effect of A. melanocarpa extract on various parameters of hemostasis. METHODS: Adenosine 5'-diphosphate (ADP)-induced aggregation was measured with turbidimetric method. Spontaneous and ADP-activated platelet adhesion were investigated using a colorimetric method. The global assay of coagulation and fibrinolysis was performed with the use of optical clotting and lysis (CL) test. Thrombin (0.5 IU/mL) and tissue plasminogen activator (60 ng/mL) were used to obtain a CL curve. The activity of thrombin and plasmin was determined by means of chromogenic substrate (S-2238, S-2251) RESULTS: The aronia extract contributed to the reduction in spontaneous and ADP-activated platelet adhesion. A significant increase in overall potential of CL as well as significant changes in key parameters of these processes (T t-thrombin time, F vo-initial plasma clotting velocity, and L max-maximum lysis) was reported. Chokeberry extract significantly inhibited the amidolytic activity of thrombin and plasmin. CONCLUSION: Our in vitro findings indicate a complex mechanism of influence of chokeberry polyphenols on platelet activity and the overall potential of CL. We confirmed that chokeberry inhibits the amidolytic activity of thrombin. It was demonstrated for the first time that chokeberry polyphenols inhibit the amidolytic activity of another serine protease, i.e., plasmin, which is the main fibrinolytic enzyme. Furthermore, our research points out a significant contribution of other plasma components and fibrinogen in the modulation of hemostasis by polyphenols.
Assuntos
Hemostasia/efeitos dos fármacos , Photinia/química , Extratos Vegetais/farmacologia , Antocianinas/análise , Antocianinas/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Adesão Celular , Fibrinólise/efeitos dos fármacos , Frutas/química , Humanos , Polifenóis/análise , Polifenóis/farmacologia , Proantocianidinas/análise , Proantocianidinas/farmacologia , Trombina/metabolismo , Ativador de Plasminogênio Tecidual/metabolismoRESUMO
UNLABELLED: Proatherogenic factors lead to activation of endothelial cells, which symptom is an increased expression of surface adhesion molecules enabling the initiation of a local inflammatory response. 7-ketocholesterol (7-KCH) is a product of oxidation of cholesterol with proven pro-apoptotic effect on the cells of the vessel wall. So far, however, the impact of 7-KCH on surface expression of adhesion molecules has not been assessed. The aim of this study was to evaluate the influence of 7-KCH on the surface expression of adhesion molecules--intracellular adhesion molecule 1 (ICAM-1, CD 54) and .platelet endothelial cell adhesion molecule 1 (PECAM-1, CD31) on human aortic endothelial cells (HAECs). MATERIAL AND METHODS: After treatment with 7-KCH surface expression of adhesion molecules on HAEC was measured with antihuman CD31 and anti-human CD54 antibodies using flow cytometer. RESULTS: 7-KCH significantly increases percentages of CD 54 on viable HEAC, but does not affect expression of CD 31. CONCLUSION: 7-KCH may enhance the initiation of a local inflammatory response in atherosclerosis by increasing the expression of ICAM-1.
Assuntos
Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Cetocolesteróis/metabolismo , Cetocolesteróis/farmacologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Aorta/citologia , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Humanos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/efeitos dos fármacosRESUMO
UNLABELLED: For 60 years, vitamin K antagonists have been used in prevention of thromboembolic complications in the course of atrial fibrillation (AF), however such therapy is associated with many inconveniences. New oral anticoagulants (NOAC), rivaroxaban and dabigatran, represent an attractive alternative to VKA. THE AIM OF THE STUDY: Yo evaluate the safety of a 6-month therapy with rivaroxaban and dabigatran in patients (pts) with persistent AF. MATERIALS AND METHODS: The analysis included 24 pts (14 females, 10 males) with nonvalvular AF and indications for oral anticoagulant therapy (CHA2DS2-VASc > or = 2, HAS-BLED < 3), hospitalized in the Clinic of Internal Diseases and Clinical Pharmacology of the Medical University of Lodz between July 2012 and September 2013. In the group of patients treated chronically with VKA, laboratory tests (GFR, creatinine, ALT AST, coagulation) were performed during their stay in the clinic. The patients were randomly assigned to the treatment with one of the new NOACs, rivaroxaban or dabigatran. After a 6-month period, the patients completed a questionnaire on their general health condition and follow-up laboratory tests were performed. RESULTS: In the group of pts. receiving dabigatran INR increased by 23% (p = 0.0002) and APTT prolongation by 91% was noted (p = 0.0004) whereas in the group of pts receiving rivaroxaban an INR increase by 17% (p = 0.04) and APTT prolongation by 32% (p = 0.0043) were observed. After a 6-month therapy, dabigatran prolongs APTT significantly more, as compared to rivaroxaban (p=0.0002). Among patients using dabigatran, 16.7% experienced the following symptoms: abdominal pain, gastritis, nausea. 8.3% patients experienced bleeding from haemorrhoids, easier bruising. In the group of patients receiving rivaroxaban, 16.7% experienced the following symptoms: nosebleeds and easier bruising; 8.3%: bleeding from gums, haematuria. 25%: pruritus, rash: 8.3%. The hazard ratio (HR) for occurrence of dyspeptic symptoms was 1.13 for dabigatran. Minor bleeding is 3.6 times more common when using rivaroxaban. CONCLUSIONS: Significant increase of INR and prolongation of APTT are observed after a 6-month therapy with rivaroxaban or dabigatran. Additionally, dabigatran significantly prolongs the prothrombin time. Despite the fact that dabigatran caused larger prolongation of APTT minor bleeding episodes occurred more frequently in patients treated with rivaroxaban. No worsening of kidney or liver function was observed during the 6-month therapy with rivaroxaban or dabigatran. Rywaroxaban more frequently causes minor bleeding, whereas treatment with dabigatran is associated with more frequent gastrointestinal adverse symptoms.
Assuntos
Fibrilação Atrial/tratamento farmacológico , Benzimidazóis/uso terapêutico , Morfolinas/uso terapêutico , Tiofenos/uso terapêutico , Tromboembolia/prevenção & controle , beta-Alanina/análogos & derivados , Idoso , Antitrombinas/efeitos adversos , Antitrombinas/uso terapêutico , Fibrilação Atrial/complicações , Benzimidazóis/efeitos adversos , Dabigatrana , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Gastroenteropatias/induzido quimicamente , Hemorragia/induzido quimicamente , Humanos , Masculino , Morfolinas/efeitos adversos , Rivaroxabana , Tiofenos/efeitos adversos , Tromboembolia/etiologia , beta-Alanina/efeitos adversos , beta-Alanina/uso terapêuticoRESUMO
UNLABELLED: The incidence of atrial fibrillation (AF) and of thromboembolic complications increases along with age. This is also the case for cognitive function disturbances; therefore their occurrence in patients (pts) with AF may hamper control of anticoagulant therapy and maintenance of therapeutic INR values. The aim of the study was to evaluate the effect of cognitive function disturbances on implementation and monitoring of the treatment with oral vitamin K antagonists (VKA) in patients with AF. The relationship between the level of cognitive function disturbances and the severity of experienced AF symptoms was defined. MATERIAL AND METHODS: The analysis included a group of 93 pts (41 males, 52 females, mean age: 76.8) with a diagnosis of AF and with indications for anticoagulation treatment with VKAs (CHA2DS2VASc > or = 2, HAS-BLED < 3), referred to the Clinic of Internal Diseases and Clinical Pharmacology of the Medical University of Lodz. In a group of pts (n = 46) treated chronically with VKAs, mean INR values at admission to the hospital were calculated and the number of results falling within the therapeutic range of 2-3, by the severity of cognitive disturbances, was analyzed. Cognitive abilities were assessed with the Mini Mental State Examination Scale (MMSE) (MMSE-Mini-mental state examination). The EHRA (European Heart Rhythm Association) classification was used to assess AF-related complaints. RESULTS: The 93 studied subjects were divided into 3 groups: group I with normal cognitive function (MMSE = 24-27) - n = 35; group II with disturbances of cognitive function without dementia (MMSE = 24-26) - n = 35 and group III with dementia (MMSE < 24) - n = 23.66% of pts with normal MMSE result were referred to the hospital because AF-related symptoms and in the group of patients with MMSE < 24 these symptoms were the cause of hospitalization in 23% of pts. Despite the fact that all patients had indications for VKAs, this treatment was not started in 40%, 51.4% and 65% of pts in group I, II and III, respectively. At admission to the hospital, therapeutic level INR values were found only in 34.8% of AF pts. 49% of pts were treated with VKAs in total. In group II, a high percentage of patients (43%) treated with aspirin was found in spite of high thromboembolic risk and no contraindications to VKAs. About 23% of pts with a normal MMSE result and 14% of pts in group II experienced AF-related symptoms preventing them from normal functioning and performing daily activities (EHRA IV). Nobody in group III reported severe AF-related symptoms. CONCLUSIONS: Along with the advancing age, there is an increase of the incidence of persistent and fixed atrial fibrillation, of the risk of thromboembolic complications and of the severity of cognitive function disturbances. Treatment with oral vitamin K antagonists was implemented much less frequently among patients with atrial fibrillation and cognitive function disturbances, as compared to the patients with normal cognitive function. The MMSE test should be routinely performed in patients with atrial fibrillation to monitor the efficacy and safety of the treatment with oral vitamin K antagonists properly. In patients with disturbances of cognitive function, significantly lower reportability of AF-related complaints was shown, as compared to individuals without these disturbances. Patients with normal MMSE result were referred to the hospital because AF-related symptoms, in the group of patients with MMSE < 23 the main reason for hospitalization was the severity of the symptoms heart failure. ECG should be a routine test performed in elderly patients with cognitive function disturbances or with dementia to detect atrial fibrillation.
Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Transtornos Cognitivos/epidemiologia , Demência/epidemiologia , Tromboembolia/epidemiologia , Vitamina K/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Transtornos Cognitivos/tratamento farmacológico , Comorbidade , Monitoramento de Medicamentos , Uso de Medicamentos , Eletrocardiografia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Diabetes patients often suffer chronic vascular complications resulting from endothelial dysfunction, smooth muscle cell (SMC) proliferation, inflammation and disturbed oxidative balance. Empagliflozin is one of three approved sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes mellitus. THE AIM OF THIS STUDY: was to determine the protective and repairing effect of EMPA in a model of vascular endothelial and SMC damage with 25-hydroxycholesterol (25-OHC). METHODS: Human umbilical vascular endothelial cells (HUVECs) and SMCs were treated with compounds which induce DNA single-strand breaks (SSBs) and subjected to comet assay. Oxidative DNA damage was detected using endonuclease III (Nth) or human 8 oxoguanine DNA glycosylase (hOOG1). Reactive oxygen species (ROS) formation was determined by the fluorescence of a 6-carboxy-2',7'-dichlorodihydrofluoresce probe in diacetate (H2DCFDA). RESULTS: 25-OHC-stimulated SMCs showed greater resistance to ROS generation and DNA damage compared to HUVECs. In both experimental models, EMPA treatment was associated with lower ROS production and DNA damage, including oxidative damage to purines and pyrimidines. This effect was not dose-dependent. EMPA was found to counteract this DNA damage by inhibiting ROS production. CONCLUSIONS: It appears that the EMPA induced indirect repair of DNA by inhibiting ROS production.
Assuntos
Diabetes Mellitus Tipo 2 , Células Endoteliais , Humanos , Espécies Reativas de Oxigênio/metabolismo , Células Endoteliais/metabolismo , Dano ao DNA , Estresse Oxidativo , Colesterol , DNA/metabolismoRESUMO
Statins, also known as HMG-CoA reductase inhibitors, are one of the most potently prescribed and thoroughly researched medications, predominantly utilized for managing cardiovascular diseases by modulating serum cholesterol levels. Despite the well-documented efficacy of statins in reducing overall mortality via attenuating the risk of cardiovascular diseases, notable interindividual variability in therapeutic responses persists as such variability could compromise the lipid-lowering efficacy of the drug, potentially increasing susceptibility to adverse effects or attenuating therapeutic outcomes.This phenomenon has catalysed a growing interest in the scientific community to explore common genetic polymorphisms within genes that encode for pivotal enzymes within the pharmacokinetic pathways of statins. In our review, we focus to provide insight into potentially clinically relevant polymorphisms associated with statins' pharmacokinetic participants and assess their consequent implications on modulating the therapeutic outcomes of statins among distinct genetic carrier.
Assuntos
Doenças Cardiovasculares , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Farmacogenética , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/induzido quimicamente , Polimorfismo GenéticoRESUMO
Heterozygous familial hypercholesterolemia (HeFH) is a common autosomal-dominant inherited disorder associated with atherosclerotic cardiovascular disease (ASCVD). HeFH subjects have a higher lipoprotein(a), i.e. Lp(a), concentration than the general population. Patients with FH are exposed to elevated levels of LDL from birth and ox-LDL may induce other oxidation pathways. The aim of the study was to determine the levels of markers of oxidative stress and DNA damage in patients with HeFH and describe the effect of Lp(a) on the resulting damage. Higher DNA damage was identified in patients with HeFH compared to the normolipidemic ones, and ASCVD was associated with greater damage. Oxidative stress markers were elevated in HeFH patients; however, only ox-LDL was higher in the ASCVD group and its level correlated with DNA damage. A positive correlation was found between DNA damage and Lp(a) concentration in the HeFH patients. Higher levels of Lp(a) were associated with greater DNA damage, especially in patients with HeFH and ASCVD. In HeFH patients, the optimal Lp(a) cut-off point associated with ASCVD is > 23.45 nmol/L, i.e. much lower than for the general population; however this cut-off point needs validation in a larger group of HeFH patients.
Assuntos
Aterosclerose , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Humanos , Lipoproteína(a)/genética , Hiperlipoproteinemia Tipo II/metabolismo , Hipercolesterolemia/complicações , Aterosclerose/complicações , Dano ao DNARESUMO
Lipid disorders are the most common (even 70%) and worst monitored cardiovascular risk factor (only 1/4 of patients in Poland and in CEE countries are on the low-density lipoprotein cholesterol (LDL-C) goal). To improve this, clear and simple diagnostic criteria should be introduced for all components of the lipid profile. These are the updated guidelines of the two main scientific societies in Poland in the area - the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA), which, in comparison to those from 2020, introduce few important changes in recommendations (two main lipid targets, new recommendations on LDL-C measurements, calculations new goals for triglycerides, new recommendations on remnants and small dense LDL) that should help the practitioners to be early with the diagnosis of lipid disorders and in the effective monitoring (after therapy initiation), and in the consequence to avoid the first and recurrent cardiovascular events.