UNASSIGNED: Bempedoic acid (BA) is a small-molecule first-in-class of inhibitor of ATP citrate lyase that significantly lowers low-density lipoproteins cholesterol (LDL-c) in statin-intolerant and inadequate responders. Increased serum uric acid (SUA) levels and gout incidence have been described in BA-treated patients. The aim of this systematic review was to investigate the safety of BA regarding SUA levels and gout in randomised controlled trials (RCTs).
UNASSIGNED: A search on 7 databases was performed from inception to May 4, 2023. RCTs of BA monotherapy or combination with other lipid-lowering treatment (LLT) in patients with increased LDL-c were included. Dual data extraction was performed with disagreements resolved through consensus. Due to the methodological purpose of this review risk-of-bias assessment of studies was not performed.
UNASSIGNED: 6 Phase 3 RCTs (N = 17,975 patients of which 9,635 received BA) 9 Phase 2 RCTs (N = 362 patients of which 170 received BA) and an open-label extension of a Phase 3 RCT were included. Gout and/or hyperuricemia were not mentioned as exclusion criteria, previous/current use of urate-lowering therapies (ULT) and/or colchicine and/or dietary patterns were not reported. Phase 3 RCTs: 2 studies specified the number of patients experiencing hyperuricemia over the study period (BA: 4.9%-11%; placebo: 1.9%-5.6%) and the effect size was significant only in 1 study (OR = 2.0, 95% CI 1.8-2.3). Four RCTs reported a higher incidence of gout in the BA arm however, when we calculated the effect size, it was small and often not significant. Two studies reported 0 cases of gout. The paucity of information about SUA levels at baseline and/or at the end of follow-up do not allow us to quantify the effect sizes for BA-induced SUA elevation. Data on gout from Phase 2 RCTs is scant.
UNASSIGNED: Data from phase 2 and 3 RCTs do not allow for confirming a clear association between BA and gout. It is conceivable that a careful assessment of SUA levels/history of gout at baseline and the concomitant use of urate-lowering agents may be instrumental to minimise the risk of new-onset gout/gout flares in patients treated with BA.

BACKGROUND: Accurate early biomarkers of oxidative stress, placenta perfusion and vascular resistance and endothelial platelet interaction for prediction of preeclampsia have not been shown to be beneficial for routine clinical use. The study of association between abnormal lipid levels in early pregnancy and preeclampsia is thus necessary in a bid to reduce the progression and severity of complications of preeclampsia.
OBJECTIVE: To determine the association between abnormal lipid levels in early pregnancy and the development of preeclampsia.
METHODS: A prospective longitudinal study involving 184 pregnant women with singleton pregnancy who met the inclusion criteria and recruited from the antenatal clinic at gestational age of < 20weeks. Their fasting blood samples were collected for the measurement serum lipid profile. They were monitored until delivery for the development of preeclampsia. The mean values of serum lipid profile were analyzed for association with pre-eclampsia using the statistical package for social sciences (SPSS) version 21.0 and P value of < 0.05 was considered statistically significant.
RESULTS: Out of 184 participants, 3 had spontaneous miscarriage and were excluded while 5 were lost to follow up. This left a total of 176 participants who completed the study, 11 of which developed preeclampsia. There was a statistically significant increase in the levels of total cholesterol (TC) and low-density lipoprotein (LDL) in the preeclamptic group. The mean serum lipid levels were 4.8 mmol/L for total cholesterol, 1.87 mmol/L for total triglycerides, 1.3 mmol/L for high-density lipoprotein and 2.67 mmol/L for low-density lipoprotein. Age and parity also showed a causal association with development of preeclampsia.
CONCLUSIONS: There was an association between elevated serum total cholesterol and low-density lipoprotein with development of preeclampsia later in pregnancy.
BACKGROUND: Les biomarqueurs précoces précis du stress oxydatif, de la perfusion et de la résistance vasculaire du placenta et de l’interaction endothéliale-plaquettaire pour la prédiction de la prééclampsie ne se sont pas révélés avantageux pour l’utilisation clinique courante. L’étude de l’association entre les taux anormaux de lipides en début de grossesse et la prééclampsie est donc nécessaire pour réduire la progression et la gravité des complications de la prééclampsie.
OBJECTIVE: Déterminer l’association entre des taux de lipides anormaux en début de grossesse et le développement de la pré- éclampsie.
UNASSIGNED: Une étude longitudinale prospective impliquant 184 femmes enceintes avec une grossesse unique qui répondaient aux critères d’inclusion et qui ont été recrutées à la clinique prénatale à l’âge gestationnel de < 20 semaines. Des échantillons de sang à jeun ont été prélevés pour mesurer le profil lipidique sérique. Elles ont été suivies jusqu’à l’accouchement pour le développement de la pré-éclampsie. Les valeurs moyennes du profil lipidique sérique ont été analysées pour leur association avec la pré-éclampsie à l’aide du progiciel statistique pour les sciences sociales (SPSS) version 21.0 et une valeur P de < 0,05 a été considérée comme statistiquement significative.
UNASSIGNED: Sur les 184 participantes, 3 ont fait une fausse couche spontanée et ont été exclues, tandis que 5 ont été perdues de vue. Il restait donc un total de 176 participantes qui ont terminé l’étude, dont 11 ont développé une prééclampsie. On a constaté une augmentation statistiquement significative des taux de cholestérol total (CT) et de lipoprotéines de basse densité (LDL) dans le groupe prééclamptique. Les taux moyens de lipides sériques étaient de 4,8 mmol/L pour le cholestérol total, 1,87 mmol/L pour les triglycérides totaux, 1,3 mmol/L pour les lipoprotéines de haute densité et 2,67 mmol/L pour les lipoprotéines de basse densité. L’âge et la parité ont également montré une association causale avec le développement de la prééclampsie.
CONCLUSIONS: Il y avait une association entre un taux élevé de cholestérol total sérique et de lipoprotéines de basse densité et le développement de la prééclampsie plus tard dans la grossesse.
UNASSIGNED: Association, Prééclampsie, Cholestérol sérique, Lipoprotéines de basse densité, Lipoprotéines de haute densité, Triglycérides, Lipides sériques.

OBJECTIVE: Recent evidence demonstrates that the atherogenic process is discontinuous. Our goal is to study changes of plaque components and local hemodynamics during atherosclerotic progression.
METHODS: The histological and immunohistochemical staining of high-fat diet rabbit aorta were evaluated at 0, 8, 10 and 12 weeks, respectively. In addition, the blood flow and LDL transport were simulated at the above four time points.
RESULTS: The plaque thickness at different characteristic regions increased at different rates. The collagen continued to increase, while the elastin, fibronectin, macrophages and smooth muscle cells increased first and then decreased. The relative surface LDL concentration decreased at 8 weeks, and then it increased first and decreased slightly. Meanwhile, the hemodynamic environment became better firstly at 8 weeks, then got slightly worse and lastly improved again.
CONCLUSIONS: The local hemodynamics and plaque components vary nonlinearly during atherosclerotic progression in rabbit aorta.

BACKGROUND: Hypertension is the leading direct cause of death in the world and one of the most important risk factors for cardiovascular disease (CVD). Elevated blood pressure (BP) often coexists with lipid disorders and is an additional factor that increases CV risk. Nowadays, we are able to distinguish low density lipoproteins (LDL) and high density lipoproteins (HDL) subfractions. Except LDL also HDL small subfractions can increase the risk of CV events. Therefore, we aimed to investigate the associations between changes of lipoprotein subfractions and the risk of hypertension development.
METHODS: In 2-year long study 200 volunteers with normal blood pressure at the age of 19-32 years were included. Each volunteer underwent detailed medical examination, 12-lead electrocardiogram was taken at rest, echocardiogram, lipid subfraction assessment (using Lipoprint®) and two 24-hour BP measurements.
RESULTS: Mean total cholesterol concentration was 189 mg/dl (4.89 mmol/l), with mean LDL concentration of 107 mg/dl (2.77 mmol/l), HDL of 63 mg/dl (1.63 mmo/l), very low-density lipoprotein (VLDL) of 40 mg/dl (1.04 mmol/l) and triglycerides (TG) of 89 mg/dl (1.00 mmol/l). Subfractions LDL 1-3 were most abundant, LDL 4-5 making up a marginal portion and LDL 6-7 were not observed. Whereas, subfractions HDL 4-6 were most abundant, in lower concentration was present HDL 1-3 and HDL 8-10. We showed that increased systolic blood pressure coreclated significantly with HDL cholesterol concentrations (p = 0.0078), HDL intermediate subgractions (p = 0.0451), with HDL-3 subfraction (p = 0.0229), and intermediate density lipoprotein-A (IDL-A) (p = 0.038). A significant correlation between increased diastolic blood pressure and HDL lipoprotein levels (p = 0.0454) was only observed.
CONCLUSIONS: Obtained results indicating correlation between total HDL levels and HDL-3 subfraction concentration (for systolic BP) and the tendency to develop hypertension.

The antioxidant effect of dinitrosyl iron complexes (DNICs) was studied in various model systems. DNICs with glutathione ligands effectively inhibited Cu2+-induced peroxidation of low density lipoproteins (LDL). The antioxidant effect of DNICs with phosphate ligands and free reduced glutathione (GSH) was less pronounced. In addition, DNICs with glutathione suppressed the formation of reactive oxygen species during co-oxidation of lecithin liposomes and glucose. Free radical oxidation in this system was induced with a lipophilic azo initiator and evaluated by luminol-dependent chemiluminescence. NO sharply stimulated chemiluminescence during co-oxidation of glucose and liposomes, thus suggesting the formation of potent oxidants under these conditions. Glutathione DNICs scavenge the superoxide radical anion generated in the xanthine-xanthine oxidase system. Superoxide production was assessed by lucigenin-dependent chemiluminescence and electron paramagnetic resonance (EPR) spectroscopy. Chemiluminescence revealed the dose-dependent character of antiradical effect of glutathione DNICs; moreover, these complexes turned out to be more efficient than GSH. EPR spectra of the adducts of the DEPMPO spin trap with free radicals suggest that the interaction of glutathione DNICs and superoxide does not result in the formation of the thiyl radical of glutathione. Here we propose a mechanism of the antioxidant action of glutathione DNICs, suggesting that unstable intermediate complexes are formed upon their interaction with superoxide or lipid radicals. Further, as a result of intramolecular rearrangement, these intermediates decompose without the free radical as the by-products.
V razlichnykh model\'nykh sistemakh issledovali antioksidantnoe deĭstvie dinitrozil\'nykh kompleksov zheleza (DNKZh). Pokazano, chto DNKZh s glutationovymi ligandami (GS-DNKZh) éffektivno ingibiruiut indutsirovannoe ionami Cu2+ perekisnoe okislenie lipoproteinov nizkoĭ plotnosti (LNP). Antioksidantnoe deĭstvie DNKZh s fosfatnymi ligandami i svobodnogo vosstanovlennogo glutationa (GSH) bylo menee vyrazhennym. Krome togo, GS-DNKZh podavliaiut obrazovanie aktivnykh form kisloroda pri sookislenii letsitinovykh liposom i gliukozy. Svobodnoradikal\'noe okislenie v étoĭ sisteme indutsirovali lipofil\'nym azoinitsiatorom (AIBN) i otsenivali s pomoshch\'iu liuminol-zavisimoĭ khemiliuminestsentsii. NO rezko stimuliroval khemiliuminestsentsiiu pri sookislenii gliukozy i liposom, chto ukazyvaet na obrazovanie v étikh usloviiakh sil\'nykh okisliteleĭ. Takzhe ustanovleno, chto GS-DNKZh perekhvatyvaiut superoksidnyĭ radikal (O2 •−), generiruemyĭ v sisteme ksantin-ksantinoksidaza. Produktsiiu O2 •− otsenivali metodami liutsigenin-zavisimoĭ khemiliuminestsentsii i spektroskopii élektronnogo paramagnitnogo rezonansa (ÉPR). S ispol\'zovaniem khemiliuminestsentsii pokazano, chto antiradikal\'noe deĭstvie GS-DNKZh bylo dozozavisimym, prichem éti kompleksy byli bolee éffektivny, chem GSH. Analiz spektrov ÉPR adduktov spinovoĭ lovushki DEPMPO c svobodnymi radikalami pozvoliaet zakliuchit\', chto pri vzaimodeĭstvii glutation-soderzhashchikh DNKZh i O2 •− ne obrazuetsia tiil\'nogo radikala glutationa. Predlozhen mekhanizm antioksidantnogo deĭstviia GS-DNKZh, predpolagaiushchiĭ obrazovanie pri ikh vzaimodeĭstvii s O2 •− ili lipidnymi radikalami nestabil\'nykh promezhutochnykh kompleksov. Dalee v rezul\'tate vnutrimolekuliarnoĭ peregruppirovki éti intermediaty raspadaiutsia bez obrazovaniia svobodnoradikal\'nykh produktov.

Depression is a major cause of morbidity and low quality of life among patients with cardiovascular disease (CVD), and it is now considered as an independent risk factor for major adverse cardiovascular events. Increasing evidence indicates not only that depression worsens the prognosis of cardiac events, but also that a cross-vulnerability between the two conditions occurs. Among the several mechanisms proposed to explain this interplay, platelet activation is the more attractive, seeing platelets as potential mirror of the brain function. In this review, we dissected the mechanisms linking depression and CVD highlighting the critical role of platelet behavior during depression as trigger of cardiovascular complication. In particular, we will discuss the relationship between depression and molecules involved in the CVD (e.g., catecholamines, adipokines, lipids, reactive oxygen species, and chemokines), emphasizing their impact on platelet activation and related mechanisms.

Cholesterol (Chol) interacts with lipoproteins, in order to be transported through the aqueous bloodstream. High density lipoproteins (HDL) and low density lipoproteins (LDL) transport cholesterol differently, a result that may be due to a difference in their interactions with cholesterol. Here, we investigated how the lipoprotein type affects the interaction with cholesterol by using a Langmuir trough and fluorescence microscope. We studied pure monolayers of 1) Chol, 2) LDL, and 3) HDL, and mixed monolayers of 1) Chol-LDL, and 2) Chol-HDL at air/water interfaces. Images of the Chol-LDL mixed monolayer showed many small sterol domains distributed in the non-sterol molecules (e.g. phospholids, proteins and lipids) of LDL. The sterol domains that were seen in the Chol-HDL mixed monolayer were larger in size but smaller in number than those seen in the Chol-LDL mixed monolayers. These images and the excess area, excess free energy, and free energy of mixing values obtained from the thermodynamic analysis of the surface pressure-area per molecule isotherms suggested that the cholesterol phase separated more from HDL than from LDL. Cholesterol was therefore concluded to interact with LDL better than with HDL. This more favorable interaction was explained by the presence of hydrophobic interactions between cholesterol and Apo-B, the major apoprotein of LDL.

Proinflammatory status is the risk factor for coronary atherosclerosis progression after coronary stenting (CS). Intensive statin treatment is associated with hsCRP concentration decline.
OBJECTIVE: to evaluate prognostic significance of preprocedural hsCRP level reduction with intensive statin regimen for coronary atherosclerosis progression during one year after CS.
METHODS: We enrolled 102 patients with stable angina who were on list for scheduled CS. Group I (n=37) patients received atorvastatin 80 mg for 7 days before and 3 months after CS with further dose adjustment according to LDL; group II (n=65) patients received atorvastatin 20-40 mg/day for LDL goal achievement. HsCRP level was assessed at baseline, before CS and after 1, 3, 6 and 12 months. Coronary atherosclerosis progression was defined as new ≥50% stenosis or ≥30% increase of ≥20% pre - existing stenosis according to coronary angiography (CA) 1 year after CS.
RESULTS: Baseline concentration of hsCRP was comparable: 0.21 (0.13; 0.38) vs. 0.20 (0.1; 0.44) mg/dl in groups I and II, respectively (p>0.05). In group I significant hsCRP level decrease to 0.14 (0.07; 0.32) mg/dl (p.
Провоспалительный статус является фактором риска прогрессии коронарного атеросклероза (АС) после коронарного стентирования (КС). Высокоинтенсивная терапия статинами ассоциирована со снижением концентрации С-реактивного белка, измеренного высокочувствительным методом (вчСРБ). Цель исследования: определение прогностической значимости снижения предпроцедурного содержания вчСРБ на фоне высокоинтенсивной терапии статинами в отношении прогрессии коронарного АС в течение года после КС. Материалы и методы. В исследование включено 102 пациента со стабильной стенокардией напряжения перед плановым КС. Группу I (n=37) составили пациенты, получавшие 80 мг аторвастатина в течение 7 сут перед и в течение 3 мес после КС с дальнейшей коррекцией дозы с учетом содержания липопротеинов низкой плотности (ЛПНП); группу II (n=65) - пациенты, получавшие 20-40 мг/сут аторвастатина с целью достижения оптимального уровня ЛПНП. Концентрация вчСРБ определялась исходно, перед КС и через 1, 3, 6 и 12 мес. Прогрессирование коронарного АС диагностировалось при выявлении нового стеноза (≥50%) или усугублении существовавшего (≥20%) как минимум на 30% при коронароангиографии (КАГ) через год после КС. Результаты. Исходная концентрация вчСРБ была сопоставимой: 0,21 (0,13; 0,38) и 0,20 (0,1; 0,44) мг/дл (p>0,05) в группах I и II соответственно. В группе I значимое снижение вчСРБ наблюдалось после недели терапии: 0,14 (0,07;0,32) мг/дл перед КС (p.

Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme, statins, are powerful cholesterol-lowering medications and have provided outstanding contributions to the primary and secondary prevention of coronary heart disease. Low-density lipoprotein cholesterol (LDL-C) is one of the major modifiable cardiovascular risk factors, indeed, every 1.0 mmol/L (38.7 mg/dL) reduction in LDL cholesterolaemia corresponds to a 21% lowering in the risk of major vascular events. In this context, the pharmacological approach with PCSK9 monoclonal antibodies is considered a promising non-statin therapeutic option for the management of lipid disorders in patients with persistent cardiovascular risk, including patients with diabetes mellitus. Data from two large clinical trials have indisputably demonstrated the efficacy of alirocumab and evolocumab in preventive major adverse cardiovascular events in high risk, secondary-prevention patients with clinical manifestation of atherosclerotic cardiovascular diseases. Finally, PCSK9 monoclonal antibodies did not increase the risk of serious adverse events, neurocognitive events, new-onset of diabetes, muscle-related events, or myalgia.

apoB exists as apoB100 and apoB48, which are mainly found in hepatic VLDLs and intestinal chylomicrons, respectively. Elevated plasma levels of apoB-containing lipoproteins (Blps) contribute to coronary artery disease, diabetes, and other cardiometabolic conditions. Studying the mechanisms that drive the assembly, intracellular trafficking, secretion, and function of Blps remains challenging. Our understanding of the intracellular and intraorganism trafficking of Blps can be greatly enhanced, however, with the availability of fusion proteins that can help visualize Blp transport within cells and between tissues. We designed three plasmids expressing human apoB fluorescent fusion proteins: apoB48-GFP, apoB100-GFP, and apoB48-mCherry. In Cos-7 cells, transiently expressed fluorescent apoB proteins colocalized with calnexin and were only secreted if cells were cotransfected with microsomal triglyceride transfer protein. The secreted apoB-fusion proteins retained the fluorescent protein and were secreted as lipoproteins with flotation densities similar to plasma HDL and LDL. In a rat hepatoma McA-RH7777 cell line, the human apoB100 fusion protein was secreted as VLDL- and LDL-sized particles, and the apoB48 fusion proteins were secreted as LDL- and HDL-sized particles. To monitor lipoprotein trafficking in vivo, the apoB48-mCherry construct was transiently expressed in zebrafish larvae and was detected throughout the liver. These experiments show that the addition of fluorescent proteins to the C terminus of apoB does not disrupt their assembly, localization, secretion, or endocytosis. The availability of fluorescently labeled apoB proteins will facilitate the exploration of the assembly, degradation, and transport of Blps and help to identify novel compounds that interfere with these processes via high-throughput screening.