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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: It is hypothesized that statin therapies might be connected with an increased risk of sleep disturbances. The objective of the study was to examine the association between use of statins (atorvastatin and rosuvastatin) and the risk of sleep disturbances compared with a group of patients who do not receive statin therapy. Additionally, we compared the effect of atorvastatin and rosuvastatin on sleep quality. Material and methods: We examined 135 patients (62 males, 73 females, mean age: 71.1 ± 10.2) with indications for chronic statin therapy (85 patients taking atorvastatin, 50 patients taking rosuvastatin) and 65 individuals without statin therapy as the control group (23 males, 42 females, mean age: 65.8 ± 11.6). The effect of statin on sleep parameters was assessed using the Athens Insomnia Scale (AIS), the Pittsburgh Sleep Quality Index (PSQI), and the Insomnia Severity Index (ISI). The exclusion criteria were use of hypnotic drugs, obstructive sleep apnoea, decompensated heart failure, and prostatic hyperplasia. Results: Our results showed that patients during atorvastatin or rosuvastatin therapy obtain a significantly higher number of points in the following: AIS compared to the control group (p < 0.001, p < 0.01), PSQI compared to the control group (p < 0.001), and ISI compared to the control group (p < 0.001, p < 0.05). Patients during atorvastatin or rosuvastatin therapy obtain a significantly higher number of points in the AIS in the first 5 questions about sleep-related symptoms compared to the control group. Conclusions: This study indicated that patients taking atorvastatin or rosuvastatin reported sleep disturbances more often than patients without statin therapy. [ABSTRACT FROM AUTHOR]

Introduction: Experimental studies have confirmed the potential vasculoprotective effects of melatonin. The aim of the study was to evaluate the influence of melatonin and its modulative role on 7-ketocholesterol-induced changes in human aortic endothelial cells (HAECs) and human aortic smooth muscle cells (HuAoSMCs). Materials and methods: The real-time cell electric impedance sensing (xCELLigence) system was used to measure cell impedance, while flow cytometry was employed to assess viability and apoptosis. Results: It was found that melatonin did not change the impedance and viability of HuAoSMCs, nor did it inhibit their 7-ketocholesterol-induced apoptosis. Melatonin decreased the impedance of HAECs. However, this effect was not attributed to cellapoptosis. In addition, it did not prevent the 7-ketocholesterol--induced decrease in HAEC impedance. Nevertheless, pretreatment with melatonin at concentrations of 10 nM and 100 nM attenuated the apoptosis caused by 7-ketocholesterol. Conclusions: This study confirmed the toxic effect of 7-ketocholesterol on primary human vascular wall cells, using 2 independent methods. We have demonstrated that melatonin has no barrier-protective effect, but low concentrations of melatonin may counteract the toxic effect of 7-ketocholesterol on HAECs through the inhibition of apoptosis. Melatonin has no significant effect on the impedance and viability of HuAoSMCs. [ABSTRACT FROM AUTHOR]

Background: The aging of our societies leads to a higher prevalence of multimorbidity and therefore polypharmacy, which often results in inappropriate drug treatment. To address this issue, numerous listing approaches, such as the Fit fOR The Aged (FORTA) list have been developed. FORTA's positive impact on the quality of medications and relevant clinical outcomes has been shown. Based on new emerging evidence and experiences with the existing FORTA lists, we aimed to update the FORTA lists in several European countries/regions. Methods: Two-step Delphi consensus procedures were conducted in Poland, UK/Ireland, Italy, Spain, the Nordic countries, The Netherlands and France. The existing European FORTA lists served as survey proposals. Results: Thirty-two experts agreed to take part in this study (return rate: 96.9%). The country/region-specific overall consensus for all items and participants after the first round was > 90%. FORTA lists from six participating countries, plus the FORTA list for the German-speaking countries, were collated into the new EURO-FORTA List, which now contains 267 items aligned to 27 indications. Three items were added to the EURO-FORTA List, and no drugs were deleted. Eight FORTA items were relabeled, and 96.9% of the labels remained unchanged. Conclusion: In this study, seven new country/region specific FORTA lists, as well as a new overarching EURO-FORTA List, were developed. An overall increase in the mean consensus coefficient and increases for all disease-specific mean consensus coefficients show a wider consensus among participants. The new lists have the potential to improve drug therapy in older people internationally. [ABSTRACT FROM AUTHOR]

Introduction: Experimental studies have confirmed the potential vasculoprotective effects of melatonin. The aim of the study was to evaluate the influence of melatonin and its modulative role on 7-ketocholesterol-induced changes in human aortic endothelial cells (HAECs) and human aortic smooth muscle cells (HuAoSMCs). Materials and methods: The real-time cell electric impedance sensing (xCELLigence) system was used to measure cell impedance, while flow cytometry was employed to assess viability and apoptosis. Results: It was found that melatonin did not change the impedance and viability of HuAoSMCs, nor did it inhibit their 7-ketocholesterol-induced apoptosis. Melatonin decreased the impedance of HAECs. However, this effect was not attributed to cell apoptosis. In addition, it did not prevent the 7-ketocholesterol--induced decrease in HAEC impedance. Nevertheless, pretreatment with melatonin at concentrations of 10 nM and 100 nM attenuated the apoptosis caused by 7-ketocholesterol. Conclusions: This study confirmed the toxic effect of 7-ketocholesterol on primary human vascular wall cells, using 2 independent methods. We have demonstrated that melatonin has no barrier-protective effect, but low concentrations of melatonin may counteract the toxic effect of 7-ketocholesterol on HAECs through the inhibition of apoptosis. Melatonin has no significant effect on the impedance and viability of HuAoSMCs. [ABSTRACT FROM AUTHOR]

Atherosclerosis and cardiovascular events can be prevented, or treated, using statin therapy, either alone or in combination with ezetimibe. Chronic inflammation, vascular proliferation, and the development of atherosclerosis are also influenced by 25-hydroxycholesterol (25-OHC). The aim of the study was to compare the direct pleiotropic effects of two commonly-used statins (atorvastatin, rosuvastatin), ezetimibe, and their combinations, on the mRNA expression of pro-inflammatory IL1β, IL-18 and IL-23 and anti-inflammatory TGFβ, IL-35 (EBI3, IL-12 subunits), IL-10 and IL-37, in endothelial cells damaged by 25-OHC. It also analyzed IL-35 expression at the protein level. HUVECs were stimulated with atorvastatin (5 μM), rosuvastatin (10 μM), ezetimibe (1.22 μM), atorvastatin-ezetimibe (5 μM + 1.22 μM) or rosuvastatin-ezetimibe (10 μM + 1.22 μM), with or without pre-incubation with 10 μg/mL 25-OHC. mRNA expression was analyzed by real-time PCR. The protein level of IL-35 was analyzed by ELISA. In the pre-stimulated HUVECs, atorvastatin and rosuvastatin decreased mRNA expression of IL1β, IL-18, IL-23, TGFβ, IL35 and increased mRNA expression of IL-10 and IL-37 compared to 25-OHC. Furthermore, only incubation with rosuvastatin and rosuvastatin-ezetimibe decreased IL-35 mRNA and protein levels. Ezetimibe down-regulated only IL1β. Treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe reversed the effect of 25-OHC in IL1β, IL-18 and IL-35 mRNA expression. In conclusion, rosuvastatin has the strongest anti-inflammatory effects and is the best at reducing the effect of oxysterols. Both statins exert a greater anti-inflammatory effect than ezetimibe. The anti-inflammatory effect of the combination therapies appears to be based on the effects of the statins alone and not their combination with ezetimibe. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (Hp) Gram-negative bacteria cause gastritis or gastric ulcers. They may be involved in the development of systemic diseases i.e. coronary heart disease (CHD). Both Hp infection and CHD are related to inflammation accompanied by C-reactive protein (CRP), tumor necrosis factor alfa (TNF-α) and homocysteine. Low density lipoprotein (LDL) and triglicerides are a classic risk factors of CHD. Infrared spectroscopy has been introduced for monitoring chronic infections or endogenous disorders using specific absorption bands for biocomponents typed as diagnostic markers. In this study we selected specific motives of infrared radiation (IR) spectra for the sera from CHD patients infected with Hp. In total 141 sera were used: 90 from patients with CHD, all Hp positive, and 51 from healthy donors, 32 Hp negative and 21 Hp positive. Hp status was evaluated by anti-Hp IgG antibodies and/or 13C urea breath testing. IR spectra were measured using FT-IR/FT-NIR Spectrum 400 spectrometer (PerkinElmer) chemometrically analyzed using artificial neural networks and they showed differences in absorption bands corresponding to triglicerides, CRP, homocysteine, LDL and TNF-α, and selected component groups between CHD patients infected with Hp vs healthy uninfected donors (96.15% accuracy). Triglicerides and CRP were the best biomarkers linking Hp infection with CHD. [ABSTRACT FROM AUTHOR]

Despite controversy over the protective effect of the BCG (Bacille Calmette-Guérin) vaccine in preventing pulmonary tuberculosis (TB) in adults, it has been used worldwide since 1921. Although the first reports in the 1930s had noted a remarkable decrease in child mortality after BCG immunization, this could not be explained solely by a decrease in mortality from TB. These observations gave rise to the suggestion of nonspecific beneficial effects of BCG vaccination, beyond the desired protection against M. tuberculosis. The existence of an innate immunity-training mechanism based on epigenetic changes was demonstrated several years ago. The emergence of the pandemic caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in 2019 revived the debate about whether the BCG vaccine can affect the immune response against the virus or other unrelated pathogens. Due to the mortality of the coronavirus disease (COVID-19), it is important to verify each factor that may have a potential protective value against the severe course of COVID-19, complications, and death. This paper reviews the results of numerous retrospective studies and prospective trials which shed light on the potential of a century-old vaccine to mitigate the pandemic impact of the new virus. It should be noted, however, that although there are numerous studies intending to verify the hypothesis that the BCG vaccine may have a beneficial effect on COVID-19, there is no definitive evidence on the efficacy of the BCG vaccine against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

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 β (TGF‐β), 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‐β, 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‐β 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‐β 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‐β, 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. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein (a)–Lp(a) has proinflammatory, prothrombotic and proatherogenic properties and may theoretically influence the course of COVID-19. Objectives: The aim of the study was to explore whether patients hospitalized due to COVID-19 with Lp(a) ≥30mg/dl may develop a worse course of the disease, increased incidence of thromboembolic complications, intubation and ICU hospitalization or death. Patients and methods: A retrospective analysis was performed of 124 patients hospitalized due to COVID-19 in the Department of Internal Diseases and Clinical Pharmacology between 29 November 2020 and 15 April 2021. The only exclusion criterion was age≥80 years. Patients were divided into two groups: 1. COVID-19 patients with Lp(a) <30mg/dl regarded as not elevated n = 80; 2. COVID-19 patients with Lp(a) ≥30 regarded as elevated n = 44. Results: A total of 124 COVID-19 patients were included in the study (66 men and 58 women) with a mean age of 62.8±11 years. COVID-19 patients with elevated Lp(a) level had significantly longer hospitalization time (11 vs. 9.5 days; p = 0.0362), more extensive radiological changes in CT scan (35 vs. 30%; p = 0.0301) and higher oxygen demand on admission (8 vs. 5L/min; p = 0.0428). Elevated Lp(a) was also associated with significantly higher OR for High Flow Nasal Oxygen Therapy (HFNOT) OR = 3.5 95%CI(1.2;8.9), p = 0.0140, Intubation and ICU OR = 4.1 95%CI(1.1;15.2) p = 0.0423, Death OR = 2.8 95%CI(0.9;8.5), p = 0.0409. Conclusions: Elevated Lp(a) might be one of the factors which contribute to a more severe course of COVID-19; however, further studies including larger groups of patients are needed. [ABSTRACT FROM AUTHOR]

Background: Molecular mimicry between Helicobacter pylori (Hp) and the host components resulting in induction of cross-reacting antibodies has been suggested as accessory mechanism in the development of coronary heart disease (CHD). A potential target for antibodies induced during Hp infection by the components of these bacteria might be amino acid sequence TVLLPVIFF (P1) of tumor necrosis factor receptor (TNFR), which is exposed on vascular endothelium and immunocompetent cells, driving inflammation. Aim: To examine whether anti-P1 IgG are induced during Hp infection in CHD patients. Methods: Sera from CHD patients infected with Hp (54) vs. sera of uninfected healthy donors (22) were tested by the ELISA for anti-H. pylori antibodies, anti-P1 IgG, and for antibodies towards control sequence IAKEGFEKIS (P2). Sera of Caviae porcellus infected experimentally with Hp (30) or uninfected (10) were included into this study. The same serum samples, which were positive for anti-P1 IgG, were adsorbed with Hp and then subjected to the ELISA. The biological activity of anti-P1 IgG was assessed in complement (C1q) binding assay. Results: Sera of 43 CHD patients seropositive for anti-Hp IgG contained anti-P1 IgG binding C1q. Additionally, 10 serum samples of animals seropositive for anti-Hp IgG contained anti-P1 IgG. Anti-P1 IgG in tested sera were neutralized by their adsorption with Hp. Conclusion: In CHD patients infected with Hp, antibodies cross-reacting with TNFR common sequence are produced. Further studies are necessary to define immunogenic Hp determinants and to confirm possible cellular effects of cross-reacting antibodies. [ABSTRACT FROM AUTHOR]

Rivaroxaban is one of the direct factor Xa inhibitors. Its function in the inactivated coagulation cascade is unclear. The aim of the study was to assess the effect of rivaroxaban on the endothelial integrity and inflammatory properties of endothelial cells stimulated by 25-hydroxycholesterol (25-OHC). HUVECs were stimulated with 25-OHC, rivaroxaban and 25-OHC+ rivaroxaban. HUVEC integrity and permeability were measured using the xCELLigence system and paracellular flux assay. The mRNA expression of tissue factor, ICAM-1, VEGF, IL-33, MCP-1, TNF-α was analyzed in the real-time PCR. Apoptosis and viability were measured by flow cytometry. The VEGF protein concentration was assessed by ELISA. The confocal microscope was used to evaluate the expression of VE-cadherin in endothelial cells. 25-OHC decreased endothelial cell integrity and increased the mRNA expression of IL-33, tissue factor, ICAM-1, MCP-1, VEGF, TNF-α as compared to unstimulated controls. Following the stimulation with rivaroxaban, HUVEC restored integrity disrupted by 25-OHC (p <.01). In HUVECs pre-stimulated with oxysterol, rivaroxaban decreased mRNA expression of IL-33, TNF-α, chemokines MCP-1, ICAM-1, VEGF and tissue factor (p <.01). Rivaroxaban 100 mg/ml+25-OHC increased the VE-cadherin expression in endothelium as compared to 25-OHC (p <.05). Our finding suggests that rivaroxaban may restore the endothelial barrier and inhibit the inflammatory activation caused by oxysterol in vitro. [ABSTRACT FROM AUTHOR]

Dyslipidemia, atherosclerosis, and cardiovascular events can be prevented, or treated, using statins, alone or in combination with ezetimibe. The aim of the study was to compare the direct pleiotropic effects of two commonly-used statins (atorvastatin, rosuvastatin), ezetimibe and their combinations on endothelial cells damaged by oxidized cholesterol. HUVEC cultures were stimulated for 20 hours with atorvastatin (5 μM; 2793 ng/mL), rosuvastatin (10 μM; 4815 ng/mL), ezetimibe (1.22 μM; 500 ng/mL), atorvastatin plus ezetimibe (5 μM + 1.22 μM; 2793 ng/mL + 500 ng/mL) and rosuvastatin plus ezetimibe (10 μM + 1.22 μM; 4815 ng/mL + 500ng/mL) in separate groups, with or without 25-hydroxycholesterol pre-incubation (24.83 μM; 10 μg/mL; four hours then washout). HUVEC integrity was measured in the RTCA-DP xCELLigence system. The mRNA expression and protein levels of ZO-1, OCLN, ICAM-1 were analyzed by real-time PCR and ELISA. Pre-incubation with 25-OHC resulted in decreased endothelial cell integrity (p<0.001), decreased expression of ZO-1 mRNA (p<0.05) and protein levels (p<0.05), OCLN mRNA (p<0.05) and protein levels (p<0.05) and increased ICAM-1 mRNA (p<0.001) and protein levels (p<0.001) compared to the control group. Incubation with rosuvastatin (12h p<0.01; 24h p<0.001) and atorvastatin (only 12h p<0.05) restored HUVEC integrity. Subsequent incubation with rosuvastatin increased ZO-1 mRNA (p<0.001) and protein (p<0.001) levels. Subsequent addition of ezetimibe increased ZO-1 mRNA level (p<0.001) but not protein level. Furthermore, only incubation with rosuvastatin increased OCLN mRNA (p<0.05) and protein (p<0.05) levels. In each drug-stimulated group, both ICAM-1 mRNA and protein levels were reduced after initial incubation with oxysterol (p<0.05). 25-hydroxycholesterol disrupts endothelial integrity, decreases the mRNA and protein levels of tight junction, and increases those of intercellular adhesion molecules. Both rosuvastatin and atorvastatin can improve endothelial integrity, but only rosuvastatin can completely abolish the effect of oxysterol. The combination of statins with ezetimibe has less direct effect on the endothelial barrier than the statins alone. [ABSTRACT FROM AUTHOR]

Background: HIV patients are at increased cardiovascular risk while available European cardiovascular recommendations are ambiguous. Methods: Retrospective analysis of 389 HIV-patients was conducted. Cardiovascular risk was determined by D:A:D, Framingham and SCORE scales. Patients were divided into risk groups as recommended by EACS 2019, PTN AIDS 2019 and ESC/EAS 2019 Guidelines and hypolipemic treatment was evaluated. Results: In total, 389 HIV-positive patients took part in the study, most of whom were men (n = 312, 80.4%), mean age 41.69±10years. Mean lipid levels among all HIV patients: Tch:177.2±36mg/dl, HDL:48.9±18mg/dl, LDL:103.8±31mg/dl, TG:143.3±81mg/dl, AIP:0.45±0.3, non-HDL:129.2±36 mg/dl. Most of the participants (n = 360, 92.5%) were assigned to the high cardiovascular risk group according to ESC/EAS and PTN AIDS guidelines. The achievement of therapeutic LDLs according to ESC/EAS was 10.3% for those at very high cardiovascular risk (8.7% on lipid lowering treatment vs. 16.7% without hypolipemic drugs) and 12.0% (5.8% treated vs. 13.6% untreated) at high cardiovascular risk; according to PTN AIDS,17.2% achievement was noted by the very high-risk group (13% treated vs. 33.3% untreated), and 45.9% for the high-risk group (37.7% treated vs. 48.0% untreated); according to EACS Guidelines, 2.5% achievement in secondary prevention (3.8% treatedvs. 0% untreated) and 24.7% in primary prevention (22.2% treated vs. 26.1% untreated). Mean doses of statins were 8.75mg±6mg (Rosuvastatin) and 22.35±19mg (Atorvastatin). Conclusions: The achievement of therapeutic LDLs by all recommendations is unsatisfactory, and generally worse in patients on lipid lowering therapy. Hypolipemic treatment of our HIV patients is based on low doses of statins, even in secondary prevention. [ABSTRACT FROM AUTHOR]

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Postprandial hypertriglyceridemia is an independent risk factor for cardiovascular disease. The aim of this study was to assess the effects of a single fat-rich meal on barrier functions and inflammatory status on human umbilical vascular endothelial cells (HUVECs), furthermore we assess the effects of mixture of palmitic acid and 25-hydroxycholesterol (PA +25OHCH) on integrity of endothelial cells and their inflammatory properties. HUVECs were induced with serum of healthy volunteers taken before, and 3 h after, the consumption of a meal with a standardized daily required dose of fats. In addition, endothelial cells were induced with PA +25OHCH (800 μM/L+10 μg/mL). Total cholesterol, triglycerides (TGs), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high sensitivity c-reactive protein, and glucose were measured at fasting and postprandially. HUVEC integrity was measured in the RTCA-DP xCELLigence system. mRNA expression of interleukin (IL)-33, IL-32, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), CX3C-chemokine, vascular endothelial growth factor (VEGF) occludin, and VE-cadherin was analyzed by real-time polymerase chain reaction. Viability and apoptosis were assessed in flow cytometry. The level of VEGF and IL-33 in fasting and postprandial serum was assessed by enzyme-linked immunosorbent assay (ELISA). Three hours after consumption of a fatty meal, all patients displayed increased levels of TGs and Toll-like receptors (110 ± 37 mg/dL versus 182 ± 64 mg/dL P < 0.05) (24 ± 11 mg/dL versus 42 ± 14 mg/dL P < 0.05). Postprandial serum and PA +25OHCH caused >20% decrease of HUVEC integrity than fasting serum (P < 0.001). HUVEC disintegration was accompanied by a decrease of occludin mRNA expression as compared with fasting serum (P < 0.05). The fatty meal affected neither VE-cadherin mRNA expression nor its apoptosis (P > 0.05). Mixture of PA +25OHCH caused decrease of VE-cadherin mRNA expression as compared with fasting serum (P < 0.01). PA +25OHCH did not affect HUVEC apoptosis (P > 0.05). Postprandial serum and PA +25OHCH caused increase of IL-33, MCP-1, ICAM-1, IL-32, VEGF, and CX3C-chemokine mRNA expression as compared with fasting serum (P < 0.05). Moreover, level of VEGF in fatty serum was significantly higher (P < 0.001). Postprandial lipemia after a single fatty meal may destabilize the endothelial barrier and initiate inflammatory processes. [ABSTRACT FROM AUTHOR]

Atherogenesis is associated with chronic gut infections; however, the mechanisms are not clear. The aim of the study was to determine whether lipopolysaccharide of E. coli (E. coli LPS) may affect endothelial barrier and modify IL‐10 expression in dendritic cells (DCs). Human umbilical vein endothelial cells (HUVECs) and monocyte‐derived DCs were treated with E. coli LPS, apolipoprotein B100 (ApoB100) and 7‐ketocholesterol (7‐kCH) – harmful oxidized form of cholesterol. The effect of E. coli LPS, 7‐kCH and ApoB100 on the barrier functions of HUVECs in real‐time cell electric impedance sensing system (RTCA‐DP) was assessed. Furthermore, the effect of 7‐kCH and ApoB100 on barrier functions of HUVECs co‐cultured with DCs previously treated with LPS was analyzed. Both E. coli LPS and 7‐kCH decreased barrier functions of HUVECs and reduced tight junction protein mRNA expression, whereas ApoB100 increased endothelial barrier. In DCs, ApoB100 and E. coli LPS decreased IL‐10 mRNA expression. In HUVECs co‐cultured with DCs treated with LPS and subsequently pulsed with ApoB100 or 7‐kCH, IL‐10 mRNA expression was lower. E. coli LPS‐exposed DCs diminished the protective effect of ApoB100 on endothelial integrity and led to the decrease in occludin mRNA expression. LPS potentially derived from gut microflora may destabilize endothelial barrier together with oxidized cholesterol and intensify the immunogenicity of ApoB100. [ABSTRACT FROM AUTHOR]

Background. FoxP3 is a marker of human T regulatory cells (Tregs), which are supposed to play an important role in the pathophysiology of atherosclerosis. Interleukin 10 (IL-10) is a cytokine with pleiotropic, immunoregulatory properties, produced mostly by Tregs and B regulatory cells. Due to their anti-inflammatory action, both Tregs and IL-10 are believed to inhibit plaque development and decrease atherosclerosis progression. The effect of hypolipidemic drugs - statins or ezetimibe - on FoxP3-positive Tregs and anti-inflammatory cytokines, such as IL-10, is still unclear. Objectives. The objective of the study was to investigate the effects of 3 different therapies of equivalent hypolipidemic activity: atorvastatin, rosuvastatin, and combination therapy of atorvastatin and ezetimibe on FoxP3-Tregs transcription factor and IL-10 mRNA expression in peripheral blood mononuclear cells (PBMCs) from patients with stable coronary artery disease (CAD). Material and methods. Sixty-five patients with diagnosed CAD participated in the study. They were randomly assigned to 3 therapeutic groups: atorvastatin at a dose of 40 mg/day (A40 group); rosuvastatin 20 mg/day (R20 group); and atorvastatin 10 mg/day combined with ezetimibe 10 mg/day (A10+E10 group). After 1 month and 6 months of therapy, the mRNA expression for FoxP3 and IL-10 in PBMCs was evaluated using real-time polymerase chain reaction (RT-PCR) and lipid parameters. Results. An improvement in lipid parameters was observed in each of the groups studied; however, hypolipidemic treatment did not induce any change in FoxP3 and IL-10 mRNA expression. After 6 months, an increase in FoxP3 mRNA expression was noted in A40 group as compared to R20 group. Conclusions. None of the therapies of equal hypolipidemic efficacy affected FoxP3 and IL-10 mRNA expression in patients with stable CAD. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (Hp) may initiate autoimmunity as a result of molecular mimicry. The aim of this study was to compare the level of IgG antibodies to a specific epitope (P1 peptide) of human heat shock protein (Hsp)60 homologous to Hp Hsp60 (HspB) in the sera of healthy donors (HD), patients with Hp‐related gastritis or coronary heart disease (CHD), uninfected or with Hp infection confirmed by rapid urease test, histological examination (dyspeptic patients) the 13C urea breath test (13C UBT), and anti‐Hp antibodies (healthy donors, CHD patients). The Anti‐P1 IgG induction by Hp was verified by adsorption of sera with these bacteria and by experimental immunization of Caviae porcellus with Hp. Cytokine secretion by THP‐1Blue™ monocytes in response to P1 was also assessed. Anti‐P1 antibodies were detected in patients with gastritis or CHD infected with Hp and they were not found in uninfected individuals or asymptomatic carriers. No antibodies were raised against P2 in any group. Reduced cross‐reactivity to P1 was exhibited by sera adsorbed with Hp. Caviae porcellus infected with Hp produced anti‐P1 autoantibodies. THP‐1XBlue™ monocytes responded to P1 by production of proinflammatory cytokines. Autoantibodies against P1 in Hp‐positive patients with gastritis or CHD and upregulation of proinflammatory cytokines by P1 may contribute to the pathogenesis of Hp infection. [ABSTRACT FROM AUTHOR]

Introduction: Atherosclerosis leading to coronary artery disease (CAD) is a chronic inflammatory condition. Interleukin 35 (IL-35) released by regulatory T cells (Tregs) has been found to be associated with CAD in the Chinese population. However, nothing is known about the relation between IL-35 concentrations and cholesterol levels. The aim of the study was to assess the levels of IL-35 in CAD patients and healthy subjects from a Caucasian population, and to analyze the relationship between IL-35 and the levels of total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, left ventricular ejection fraction (LVEF), sex and postmenopausal status.Material and Methods: Thirty-one patients with CAD and 30 healthy controls were included in the study. Levels of plasma IL-35 were analyzed by ELISA. The LVEF was assessed by transthoracic echocardiographic examination. Plasma levels of cholesterol fractions and C-reactive protein (CRP) were assessed by immunoenzymatic methods.Results: The CAD patients had higher levels of IL-35 as compared to healthy controls (58.1 ±16.6 pg/ml vs. 5.35 ±3.35 pg/ml; p < 0.001). IL-35 levels negatively correlated with total and LDL cholesterol concentrations (R = -0.31, p < 0.01) and positively correlated with HDL cholesterol in men (R = 0.53, p < 0.01). In women, IL-35 levels negatively correlated with LVEF (R = -0.29, p < 0.05) and positively with the duration of postmenopausal status (R = 0.55, p < 0.01).Conclusions: These results suggest a possible association between high levels of IL-35 and CAD. [ABSTRACT FROM AUTHOR]

Background. IL-22 is expressed at barrier surfaces, which suggests its critical role in the maintenance of normal barrier homeostasis and tissue repair. IL-22 can both promote pathological inflammation and prevent the destruction of tissues. The functional outcomes of IL-22 on vascular smooth muscle cells, which are shown to regulate immune processes within the vascular wall and which are involved in certain pathologies, have not been analyzed. Objectives. The effect of IL-22 on the expression of novel anti- and pro-inflammatory and barrier disrupting cytokines, apoptosis and the expression of adhesive molecules in human primary aortic smooth muscle cells (AoSMC) was investigated. Material and methods. Human AoSMC were induced with IL-22 for 24 h in vitro. The influence of IL-22 on IL-35 subunits EBI3 and p35, IL-33, IFN-γ and VEGF mRNA expression in Ao-SMC were assessed using real-time PCR. Additionally, the surface expression of ICAM-1 and apoptosis of AoSMC were analyzed in the flow cytometer. Results. IL-22 caused a 2- and 3-fold increase of mRNA expression of the EBI3 and p35 IL-35 subunits, and a 40% decrease of IL-33 mRNA expression in AoSMC. Additionally, IL-22 decreased ICAM-1 expression on the surface of AoSMC by 30%. However, IL-22 affected neither IFN-γ and VEGF mRNA expression in AoSMC nor their apoptosis and viability. Conclusions. Our data suggest that IL-22, which is released by Th22 and NK cells, may be an agent affecting the inflammatory response of AoSMC, and thus it may regulate immune homeostasis of the vascular wall. [ABSTRACT FROM AUTHOR]

The article presents the 2016 guidelines for the management of dyslipedemias for family physicians drafted by the Polish Lipid Association (PoLA), College of Family Physicians in Poland (CFPiP) and the Polish Cardiac Society (PCS). Topics discussed include dyslipidemias as the most common and uncontrolled risk factor for cardiovascular disease (CVD) in Poland, epidemiology of dyslipedemias in Poland, and dyslipidemia treatment targets.

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 FceRI and FceRII 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 FceRI and FceRII 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 FceRI and FceRII receptors in the human vascular endothelium. IL-4 caused respective 2- and 3-fold increases in FceRI and FceRII 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 FceRI and FceRII may allow the human vascular endothelium to respond to a specific antigen by increasing its integrity via an IgE-mediated mechanism. [ABSTRACT FROM AUTHOR]

Introduction: Pathogens, including Helicobacter pylori (Hp), have been suggested to contribute to the development of coronary heart disease (CHD), although the evidence still remains insufficient. The study was focused on the exposure of CHD patients to Hp and resulting anti-Hp heat shock protein B HspB antibody production in relation to the level of serum lipopolysaccharide binding protein (LBP) as a marker of inflammation.Material and Methods: One hundred seventy CHD patients and 58 non-CHD individuals participated in this study. Coronary angiography confirmed the atheromatic background of CHD. The panel of classical risk factors included: arterial hypertension, diabetes, total cholesterol, low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol, triglycerides, obesity and nicotinism. The Hp status was estimated by (13)C urea breath test and serology. Immunoblot and ELISA were used for screening the sera samples for anti-Hp HspB immunoglobulins (Igs) and LBP.Results: Coronary heart disease patients were exposed to Hp more frequently than non-CHD individuals. This was associated with increased levels of specific anti-Hp IgG2 and IgA as well as total IgA. Hp infected CHD and non-CHD donors produced anti-Hp HspB IgG cross-reacting with human Hsp 60. In CHD patients the LBP level was significantly higher in comparison to non-CHD donors. This was related to the severity of the disease. Type I Hp strains stimulated higher LBP levels than less pathogenic type II isolates.Conclusions: Lipopolysaccharide binding protein secreted in excess together with anti-Hp HspB, cross-reacting with human Hsp60, may increase the risk of vascular pathologies in Hp-exposed CHD patients. [ABSTRACT FROM AUTHOR]

Introduction: Statin use might be associated with an increased risk of sleep disturbances including insomnia, but the evidence regarding sleep changes following statin therapy has not been conclusive. Therefore we assessed the impact of statin therapy on sleep changes through a systematic review and meta-analysis of available randomized controlled trials (RCTs).Material and Methods: We searched MEDLINE and SCOPUS up to October 1, 2014 to identify placebo-controlled RCTs investigating the effect of statin therapy on sleep changes. A meta-analysis was performed using either a fixed-effects or a random-effect model according to the I2 statistic. Effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI).Results: Overall, the impact of statin therapy on polysomnography (PSG) indices of sleep was reported in 5 trials comprising 9 treatment arms. Overall, statin therapy had no significant effect on total sleep duration (WMD: -7.75 min, 95% CI: -18.98, 3.48, p = 0.176), sleep efficiency (WMD: 0.09%, 95% CI: -2.27, 2.46, p = 0.940), entries to stage I (WMD: 0.36, 95% CI: -0.91, 1.63, p = 0.580), or latency to stage I (WMD: -1.92 min, 95% CI: -4.74, 0.89, p = 0.181). In contrast, statin therapy significantly reduced wake time (WMD: -4.43 min, 95% CI: -7.77, -0.88, p = 0.014) and number of awakenings (WMD: -0.40, 95% CI: -0.46, -0.33, p < 0.001). Meta-regression did not suggest any correlation between changes in wake time and awakening episodes with duration of treatment and LDL-lowering effect of statins.Conclusions: The results indicated that statins have no significant adverse effect on sleep duration and efficiency, entry to stage I, or latency to stage I sleep, but significantly reduce wake time and number of awakenings. [ABSTRACT FROM AUTHOR]

Copyright of Review of Medicine / Przeglad Lekarski is the property of Wydawnictwo Przegld Lekarski / Publisher Medicine Review and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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-thrombin time, F-initial plasma clotting velocity, and L-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. [ABSTRACT FROM AUTHOR]

Objective and design: The damage of barrtier tissues, such as the vascular endothelium and intestinal epithelium, may lead to disturbances of local immune homeostasis. The aim of the study was to assess and compare the effect of oxidized cholesterols (7-ketocholesterol and 25-hydroxycholesterol) on the barrier properties of human primary aortic endothelium (HAEC) and intestinal epithelium Caco-2 cells using a real-time cell electric impedance sensing system (RTCA-DP). Materials and methods: HAEC and Caco-2 cells were stimulated with 7-ketocholesterol and 25-hydroxycholesterol by the RTCA-DP system. Apoptosis was assessed by flow cytometry and cell monolayer morphology was assessed under a light microscope. Results: 7-ketocholesterol decreased impedance (nCI) in both the endothelium and epithelium. However, the decrease was more profound in the endothelium. Similarly, although 25-hydroxycholesterol decreased nCI in both the endothelium and epithelium, the effect was weaker than that of 7-ketocholesterol, which caused extensive damage to the endothelial monolayer, while 25-hydroxycholesterol caused partial damage and did not affect the epithelial monolayer. 7-ketocholesterol, but not 25-hydroxycholesterol, increased endothelial cell apoptosis and decreased the viability of endothelial cells. However, 7-ketocholesterol and 25-hydroxycholesterol decreased epithelial cell apoptosis and increased viability. Conclusion: Oxidized cholesterols destroy the HAEC, but not the Caco-2 epithelial barrier, via cell apoptosis dependent on the site of oxidation. Damage to the endothelium by oxidized cholesterol may disrupt local homeostasis and provide open access to inner parts of the vascular wall for lipids, other peripheral blood-derived agents, and immune cells, leading to inflammation and atherogenesis. [ABSTRACT FROM AUTHOR]

Copyright of Biochemistry & Cell Biology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: A diet rich in berries is believed to play a distinct role in the prevention of metabolic diseases associated with obesity. So far, there have been no published clinical observations evaluating the influence of Aronia melanocarpa on hemostasis. The aim of our study was to investigate the effects of A. melanocarpa extract (AM) supplementation on platelet aggregation, clot formation, and lysis in patients with metabolic syndrome (MS). Methods: Middle-aged non-medicated subjects with MS ( n = 38) and 14 healthy volunteers were included in this study. Patients with MS were treated with 100 mg of AM three times daily for 2 months. Results: We observed a significant reduction in the concentration of TC, LDL-C, and TG after AM supplementation. Beneficial changes in coagulation parameters were also observed. After 1 month of AM administration, we noticed significant inhibition of platelet aggregation. However, this effect became less pronounced after 2 months of supplementation. In the case of coagulation induced by endogenic thrombin, a significant decrease in the overall potential for coagulation was induced after 1 or 2 months of supplementation. Moreover, after 1 month of AM extract supplementation, we observed a beneficial reduction in the overall potential for clot formation and fibrinolysis. Conclusions: We observed the normalization of hemostasis parameters in MS patients after both 1 and 2 months of AM administration. After 1 month of AM supplementation, we found favorable changes in regards to the overall potential for plasma clotting, clot formation, and lysis, as well as in the lipid profiles of subjects. [ABSTRACT FROM AUTHOR]

Objective: Four polyphenols: ferulic acid and p-coumaric acid (hydroxycinnamic acids), quercetin (flavonol) and cyanidin 3-glucoside (anthocyanin) were selected, and their antioxidant properties and their influence on cholesterol concentration in hypercholesterolemic and normal erythrocytes were investigated. Methods: To determine the effect of phenolic compounds, we prospectively studied cholesterol concentration, lipid peroxidation and membranes fluidity. Whole-blood and isolated erythrocytes (2% hematocrit) were incubated for 24 h with selected compounds at concentration 1, 10 and 100 μmol/L. All investigated compounds decreased lipid peroxidation in whole blood. Cyanidin 3-glucoside and quercetin showed higher antioxidant properties than hydroxycinnamic acids (ferulic acid and p-coumaric acid). Results: Incubation of whole blood of hypercholesterolemic patients with quercetin and cyanidin 3-glucoside resulted in statistically significant reduction of cholesterol concentration in erythrocytes down to 75% (at 10 μmol/L of polyphenols) and 69% (at 100 μmol/L of polyphenols) of initial values. The effect of both compounds on isolated erythrocytes was even more pronounced, reduction down to 70% (at 10 μmol/L of polyphenols) and 58% (at 100 μmol/L of polyphenols) of initial values. After incubation of isolated erythrocytes of hypercholesterolemic patients with quercetin and cyanidin 3-glucoside, increase of membrane fluidity was noticed. After incubation of isolated erythrocytes of healthy donors with investigated compounds, no changes in membrane fluidity were observed. Conclusion: Our results indicate that flavonols and anthocyanins have higher antioxidant properties and higher influence on cholesterol concentration in erythrocytes membranes than simple hydroxycinnamic acids. [ABSTRACT FROM AUTHOR]

Objective: Four polyphenols: ferulic acid and p-coumaric acid (hydroxycinnamic acids), quercetin (flavonol) and cyanidin 3-glucoside (anthocyanin) were selected, and their antioxidant properties and their influence on cholesterol concentration in hypercholesterolemic and normal erythrocytes were investigated. Methods: To determine the effect of phenolic compounds, we prospectively studied cholesterol concentration, lipid peroxidation and membranes fluidity. Whole-blood and isolated erythrocytes (2% hematocrit) were incubated for 24 h with selected compounds at concentration 1, 10 and 100 μmol/L. All investigated compounds decreased lipid peroxidation in whole blood. Cyanidin 3-glucoside and quercetin showed higher antioxidant properties than hydroxycinnamic acids (ferulic acid and p-coumaric acid). Results: Incubation of whole blood of hypercholesterolemic patients with quercetin and cyanidin 3-glucoside resulted in statistically significant reduction of cholesterol concentration in erythrocytes down to 75% (at 10 μmol/L of polyphenols) and 69% (at 100 μmol/L of polyphenols) of initial values. The effect of both compounds on isolated erythrocytes was even more pronounced, reduction down to 70% (at 10 μmol/L of polyphenols) and 58% (at 100 μmol/L of polyphenols) of initial values. After incubation of isolated erythrocytes of hypercholesterolemic patients with quercetin and cyanidin 3-glucoside, increase of membrane fluidity was noticed. After incubation of isolated erythrocytes of healthy donors with investigated compounds, no changes in membrane fluidity were observed. Conclusion: Our results indicate that flavonols and anthocyanins have higher antioxidant properties and higher influence on cholesterol concentration in erythrocytes membranes than simple hydroxycinnamic acids. [ABSTRACT FROM AUTHOR]

Experimental studies have proven that melatonin has many beneficial pleiotropic actions. The aim of this study was to assess melatonin efficacy in patients with metabolic syndrome (MS). The study included 33 healthy volunteers (who were not treated with melatonin) and 30 patients with MS, who did not respond to 3-month lifestyle modification. Patients with MS were treated with melatonin (5 mg/day, 2 hr before bedtime) for 2 months. The following parameters were studied: systolic and diastolic blood pressure (SBP, DBP), levels of glucose, serum lipids, C-reactive protein, fibrinogen, activities of antioxidative enzymes: catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), thiobarbituric acid reactive substrates (TBARS). After 2-month therapy in comparison with baseline, the following significant changes were measured: systolic blood pressure (132.8 ± 9.8 versus 120.5 ± 11.0 mmHg, P < 0.001), DBP (81.7 ± 8.8 versus 75 ± 7.4 mmHg, P < 0.01), low-density lipoprotein cholesterol (LDL-C) (149.7 ± 26.4 versus 139.9 ± 30.2 mg/dL, P < 0.05), TBARS (0.5 ± 0.2 versus 0.4 ± 0.1 μ/gHb, P < 0.01), and CAT (245.9 ± 46.9 versus 276.8 ± 39.4 U/gHb). Melatonin administered for 2 months significantly improved antioxidative defense (increase in CAT activity, decrease in TBARS level) and lipid profile (decrease in LDL-C), and lowered blood pressure. We conclude that melatonin therapy may be of benefit for patients with MS, particularly with arterial hypertension. Further studies with higher doses of melatonin or prolonged supplementation are awaited. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Presents a study which investigated the effects of simvastatin and prevastatin on peroxidation of erythrocyte plasma membrane lipids in patients with type 2 hypercholesterolemia. Materials and method; Results; Discussion.

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-β 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. [ABSTRACT FROM AUTHOR]

Metformin, one of the most frequently prescribed oral anti-diabetic drugs, is characterized by multidirectional activity, including lipid lowering, cardio-protective and anti-inflammatory properties. This study presents synthesis and stability studies of 10 novel sulfonamide-based derivatives of metformin with alkyl substituents in the aromatic ring. The potential of the synthesized compounds as glucose-lowering agents and their effects on selected parameters of plasma and vascular hemostasis were examined. Compounds with two or three methyl groups in the aromatic ring (6, 7, 9, 10) significantly increased glucose uptake in human umbilical vein endothelial cells (HUVECs), e.g., 15.8 µmol/L for comp. 6 at 0.3 µmol/mL versus 11.4 ± 0.7 µmol/L for control. Basic coagulation studies showed that all examined compounds inhibit intrinsic coagulation pathway and the process of fibrin polymerization stronger than the parent drug, metformin, which give evidence of their greater anti-coagulant properties. Importantly, synthesized compounds decrease the activity of factor X, a first member of common coagulation pathway, while metformin does not affect coagulation factor X (FX) activity. A multiparametric clot formation and lysis test (CL-test) revealed that the examined compounds significantly prolong the onset of clot formation; however, they do not affect the overall potential of clot formation and fibrinolysis. Erythrotoxicity studies confirmed that none of the synthesized compounds exert an adverse effect on erythrocyte integrity, do not contribute to the massive hemolysis and do not interact strongly with the erythrocyte membrane. In summary, chemical modification of metformin scaffold into benzenesulfonamides containing alkyl substituents leads to the formation of potential dual-action agents with comparable glucose-lowering properties and stronger anti-coagulant activity than the parent drug, metformin. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]