Antiatherogenic Properties Research Articles

The state of lipid metabolism indicators and the system of peroxidation — antioxidant protection in aluminum production workers with occupational bronchopulmonary pathology

Introduction. In aluminum production workers, the most common occupational pathology is bronchopulmonary diseases, which are characterized by the formation of comorbid pathologies. Oxidative stress plays a key role in the pathogenesis of bronchopulmonary and cardiovascular pathologies.
 The study aims to research the indicators of oxidative metabolism and antioxidant protection in aluminum production workers with occupational bronchopulmonary pathology (OBPP) during work and post-contact period.
 Materials and methods. During the study, on the basis of the therapeutic department of the clinic at East-Siberian Institute of Medical and Ecological Research, scientists examined 130 patients — workers of aluminum production, with an established professional diagnosis of the bronchopulmonary system both during work and in the post-contact period. The authors have analyzed the indicators of oxidative stress, lipid metabolism and the concentration of antibodies to oxidized low-density lipoproteins.
 Results. In patients with OBPP, decreased superoxide dismutase activity was more common during work than in the post-exposure period. About 60% of the examined patients had elevated cholesterol levels, almost 40% had higher reference values of the atherogenicity index and the content of antibodies to oxidized low-density lipoproteins. Cholesterol levels in high-density lipoproteins in individuals with OBPP in the long-term period were lower than in individuals with the same pathology during the work period.
 Conclusion. The depletion of antioxidant protection in workers in the post-contact period of the OBPP, the researchers noted in the form of a decrease in the activity of superoxide dismutase in every third person examined, which can lead to the formation of endothelial dysfunction. An increase in the fractions of atherogenic cholesterol is accompanied by a significant increase in the occurrence of a reduced level of high-density lipoprotein cholesterol, which has anti-atherogenic properties.
 Ethics. The examination of patients met ethical standards in accordance with the Helsinki Declaration of the World Association "Ethical Principles of Conducting Scientific Medical Research with Human Participation", as amended in 2000 and the "Rules of Clinical Practice in the Russian Federation", approved by Order of the Ministry of Health of the Russian Federation No. 266 of 06/19/2003. All the surveyed signed an informed consent to participate in the study. The protocol of the study was approved by the Ethics Committee of the East Siberian Institute of Medical and Environmental Research (Protocol No. 6 of 10.03.2020).

Dissecting the Impact of Vascular Smooth Muscle Cell ABCA1 versus ABCG1 Expression on Cholesterol Efflux and Macrophage-like Cell Transdifferentiation: The Role of SR-BI.

Cholesterol-laden macrophages are recognized as a major contributor to atherosclerosis. However, recent evidence indicates that vascular smooth muscle cells (VSMC) that accumulate cholesterol and transdifferentiate into a macrophage-like cell (MLC) phenotype also play a role in atherosclerosis. Therefore, removing cholesterol from MLC may be a potential atheroprotective strategy. The two transporters which remove cholesterol from cells are ABCA1 and ABCG1, as they efflux cholesterol to apoAI and HDL, respectively. In this study, the well-characterized immortalized VSMC line MOVAS cells were edited to generate ABCA1- and ABCG1-knockout (KO) MOVAS cell lines. We cholesterol-loaded ABCA1-KO MOVAS cells, ABCG1-KO MOVAS cells, and wild-type MOVAS cells to convert cells into a MLC phenotype. When we measured apoAI- and HDL-mediated cholesterol efflux in these cells, we observed a drastic decrease in apoAI-mediated cholesterol efflux within ABCA1-KO MOVAS MLC, but HDL-mediated cholesterol efflux was only partially reduced in ABCG1-KO MOVAS cells. Since SR-BI also participates in HDL-mediated cholesterol efflux, we assessed SR-BI protein expression in ABCG1-KO MOVAS MLC and observed SR-BI upregulation, which offered a possible mechanism explaining why HDL-mediated cholesterol efflux remains maintained in ABCG1-KO MOVAS MLC. When we used lentivirus for shRNA-mediated knockdown of SR-BI in ABCG1-KO MOVAS MLC, this decreased HDL-mediated cholesterol efflux when compared to ABCG1-KO MOVAS MLC with unmanipulated SR-BI expression. Taken together, these major findings suggest that SR-BI expression in MLC of a VSMC origin plays a compensatory role in HDL-mediated cholesterol efflux when ABCG1 expression becomes impaired and provides insight on SR-BI demonstrating anti-atherogenic properties within VSMC/MLC.

Phytocorrection of Age-Related Changes in the Composition of Blood Plasma, Lymph, and Interstitial Fluid.

We studied the effect of a new complex phytocomposition on age-related changes in the composition of biological fluids (blood, lymph, and interstitial fluid) in old (22-24-month-old) white Sprague-Dawley rats. A 3-month course of phytocomposition induced an increase in the volumes of interstitial fluid (IF) and plasma and stimulated lymph outflow and diuresis. In the blood and lymph, the clotting time increased, while the viscosity and all lipid indicators decreased. The phytocomposition increased the number of erythrocytes and leukocytes, the levels of immunoglobulins (except IgG) and lymphocyte subpopulations, which contributed to correction and improvement of the immune properties of the blood and lymph. Increased hydration of the tissues of the body and strengthening of the anti-atherogenic and immune properties of the lymph and blood led to recovery of the drainage and detoxification function of the lymphatic system. Due to the presence of bioflavonoids, microelements, and vitamins, the new complex phytocomposition produces a lymphotropic effect by changing the composition of the blood, lymph, and IF and stimulates fluid transport from IF into the vascular bed, thereby promoting natural lymph detoxification and increasing the immune properties of the blood and lymph.

Interbreed differences in the cholesterol profile in cattle in Western Siberia

The authors studied the leading indicators of the cholesterol profile of high-density lipoproteins (HDL-C), low-density lipoproteins (LDL-C) and total cholesterol (TC) in Black-and-White, Red Steppe and Holstein breeds of the second or third lactation, bred in large livestock farms—complexes on the territory of Western Siberia. Metabolism and concentration of lipid complexes of cholesterol status play a cardinal role in the homeostasis of cellular metabolic processes. The critical role of serum lipoproteins in cholesterol metabolism is well recognised, as is their role as predictors of cardiovascular disease. At the same time, the atherogenic effect of LRN-C is associated with the transfer of fatty acids, which act as energy substrates for ATP synthesis. Anti-atherogenic properties characterise HDL-C and have an antioxidant and anti-inflammatory effect. The concentration of HDL-C - was determined by the precipitation method of phosphotungstic acid with magnesium chloride; the level of LDL-C - by the enzymatic colourimetric direct method, total cholesterol - by the process of enzymatic hydrolysis and oxidation of CHOD-PAP using reagent kits “HDL-Cholesterol-Novo”, “LDLCholesterol-Novo-A”, “Cholesterol-Novo” (“Vector-Best, Russia. The content of OH and LDL-C in the blood serum of cows at the age of the second or third lactation bred in Western Siberia is higher than the generally accepted standard values, which reflects a different degree of adaptation to climatic conditions. Ranked series of breeds (p < 0.05) according to LDL-C: black-and-white → Holstein → red steppe, medians were 4.91; 2.77 and 2.24 mmol/l, respectively. Differences between the indicators of HDL-C and LDL-C in Black-and-White, Red Steppe and Holstein cows were established, which indicates the genetic determination of the level of lipoproteins in the blood serum. The strength of the influence of the cow breed factor on the level of HDL-C in blood serum was 29%, LDL-C - 17%.

Conventional and advanced extraction methods of some bioactive compounds with health benefits of food and plant waste: A comprehensive review

AbstractFood bioactive compounds have a beneficial biological effect on human health, fending off cancer, cardiovascular disease, metabolic syndrome, and neurodegenerative disease, among other noncommunicable diseases and neurodegenerative disorders. Secondary metabolites like polyphenols, glucosinolates, carotenoids, vitamins, terpenoids, saponins, and fibers have been linked to these health benefits due to their antioxidant, antiatherogenic, anti‐inflammatory, antimicrobial, cardioprotective, and vasodilator properties. This review comprehensively illustrates the extraction of bioactive compounds in food formulations along plant wastes and provides insight into the efficient delivery systems for health‐promoting compounds. There is an insight into how to choose which bioactive to use, how to extract them in a bioavailable state, and how to include and deliver them. Grapes, garlic, sweet potato leaves, cactus pears, beetroot, amaranth, Picea abies bark waste, olive leaves, and black plum are discussed comprehensively in terms of extraction and health benefits. The novel and emerging technologies are discussed in detail, and a comprehensive review and comparison with conventional methods are presented. The significant health benefits associated with bioactive compounds are also discussed.

Adipose tissue dysfunction serum markers are associated with high density lipoprotein size and glycation in the early stages of type 2 diabetes

BackgroundHigh-density lipoproteins (HDLs) have antiatherogenic properties related to their chemical structure. Adipose tissue (AT) influences HDL reverse cholesterol transport and plasma HDL cholesterol levels. However, whether AT dysfunction affects HDL subpopulations and their glycation in early type 2 diabetes (T2D) is still unknown.ObjectiveTo investigate the association of inflammation and AT dysfunction serum markers with the size and glycation of HDLs in normoglycemic, prediabetes, and T2D subjects.MethodsWe assessed HDL particle size and advanced glycation end-product (AGE) content in HDLs isolated from normoglycemic (n = 17), prediabetes (n = 17), and recently T2D-diagnosed (n = 18) subjects. Insulin, adiponectin, and plasminogen activator inhibitor 1 (PAI-1) were determined using the Bio-Rad Multiplex Platform, and free fatty acids (FFAs) and high sensitivity C-reactive protein (hs-CRP) were determined by standard procedures. The AT insulin resistance (ATIR) index and ATIR/adiponectin and adiponectin/leptin ratios were calculated.ResultsHDL was progressively smaller (nm) and enriched with AGE (mg-BSA-AGE/mg protein) according to the glucose categories: 8.49 and 7.5 in normoglycemic subjects, 8.44 and 12.4 in prediabetic subjects, and 8.32 and 14.3 in T2D subjects (P = 0.033 and P = 0.009 for size and AGE, respectively). In multivariable regression analysis, the ATIR/adiponectin ratio was inversely associated with HDL size (β = -0.257, P = 0.046), and the ATIR ratio was directly associated with HDL glycation (β = 0.387, P = 0.036). In contrast, adiponectin and the adiponectin/leptin ratio were not associated with alterations in HDL particles. Furthermore, HDL size was associated with resistin (β = -0.348, P = 0.007) and PAI-1 (β = -0.324, P = 0.004). HDL and AGE were related to insulin concentrations (β = 0.458, P = 0.015). Analyses were adjusted for age, sex, body mass index, triglycerides, and HDL-cholesterol.ConclusionHDL size was significantly associated with the ATIR/adiponectin ratio and inflammation, whereas glycation was more strongly related to the ATIR index. These findings have important implications for the management and prevention of cardiovascular disease in T2D patients.

Efficacy and Biomedical Roles of Unsaturated Fatty Acids as Bioactive Food Components

Abstract: Unsaturated fatty acids (UFAs) as bioactive compounds possess a wide range of biomedical functions and a lack or shortage of them may cause serious harm to human body health. Biochemically, UFAs have attracted growing interest, and this attention arises not only from biomedical reasons but also economic ones. Among these fatty acids, omega-3 and omega-6 fatty acids are considered the most efficient and safe compounds which can be used for expanding and identification of novel functionalities. They are considered essential membrane components and are associated with a variety of biological processes. For example, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as polyunsaturated fatty acids (PUFAs) play a central role in the proper functioning of the nervous system like anti-atherogenic properties and improve the functioning of the cardiovascular system. Briefly, understanding the relationship between these properties and potential biomedical applications of UFAs may help to elucidate and facilitate the development of novel pathogenesis strategies regarding their disorders in human health and diseases. This review provides the most suitable functional roles and potential mechanisms of UFAs associated with human health and nutrition.

The Role of Punicalagin and Its Metabolites in Atherosclerosis and Risk Factors Associated with the Disease.

Atherosclerotic cardiovascular disease (ACVD) is the leading cause of death worldwide. Although current therapies, such as statins, have led to a marked reduction in morbidity and mortality from ACVD, they are associated with considerable residual risk for the disease together with various adverse side effects. Natural compounds are generally well-tolerated; a major recent goal has been to harness their full potential in the prevention and treatment of ACVD, either alone or together with existing pharmacotherapies. Punicalagin (PC) is the main polyphenol present in pomegranates and pomegranate juice and demonstrates many beneficial actions, including anti-inflammatory, antioxidant, and anti-atherogenic properties. The objective of this review is to inform on our current understanding of the pathogenesis of ACVD and the potential mechanisms underlying the beneficial actions of PC and its metabolites in the disease, including the attenuation of dyslipidemia, oxidative stress, endothelial cell dysfunction, foam cell formation, and inflammation mediated by cytokines and immune cells together with the regulation of proliferation and migration of vascular smooth muscle cells. Some of the anti-inflammatory and antioxidant properties of PC and its metabolites are due to their strong radical-scavenging activities. PC and its metabolites also inhibit the risk factors of atherosclerosis, including hyperlipidemia, diabetes mellitus, inflammation, hypertension, obesity, and non-alcoholic fatty liver disease. Despite the promising findings that have emerged from numerous in vitro, in vivo, and clinical studies, deeper mechanistic insights and large clinical trials are required to harness the full potential of PC and its metabolites in the prevention and treatment of ACVD.

The Adapted POM Analysis of Avenanthramides In Silico.

POM analysis and related approaches are significant tools based on calculating various physico-chemical properties and predicting biological activity, ADME parameters, and toxicity of a molecule. These methods are used to evaluate a molecule's potential to become a drug candidate. Avenanthramides (AVNs) are promising secondary metabolites specific to Avena spp. (oat). They comprise the amides of anthranilic acid linked to various polyphenolic acids with or without post-condensation molecule transformation. These natural compounds have been reported to exert numerous biological effects, including antioxidant, anti-inflammatory, hepatoprotective, antiatherogenic, and antiproliferative properties. To date, almost 50 various AVNs have been identified. We performed a modified POM analysis of 42 AVNs using MOLINSPIRATION, SWISSADME, and OSIRIS software. The evaluation of primary in silico parameters revealed significant differences among individual AVNs, highlighting the most promising candidates. These preliminary results may help coordinate and initiate other research projects focused on particular AVNs, especially those with predicted bioactivity, low toxicity, optimal ADME parameters, and promising perspectives.

In vitro study of Nigella sativa and thymoquinone activity on endothelial activation and monocyte adhesion.

Thymoquinone (TQ) is one of the bioactive compounds in Nigella sativa (NS). Also known as black seeds/cumin, it has been postulated to possess anti-atherogenic properties. However, research on the effects of NS oil (NSO) and TQ on atherogenesis remain scarce. The aim of this study is to determine gene and protein expression of Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Endothelial-eukocyte adhesion molecule (E-selectin) in Human Coronary Artery Endothelial Cells (HCAECs). HCAECs were stimulated for 24 hours (h) with 200 µg/ml of Lipopolysaccharides (LPS) and different concentrations of NSO (55, 110, 220, 440 µg/ml) or TQ (4.5, 9.0, 18.0, 36.0 µm). The effects of NSO and TQ on gene and protein expressions were measured using multiplex gene assay and ELISA assay, respectively. Rose Bengal assay was used to analyse monocyte binding activity. NSO and TQ significantly reduced ICAM-1 and VCAM-1 gene and protein expressions. TQ showed significant reduction activity of the biomarkers in dose dependent manner. HCAECs pre-treated with NSO and TQ for 24 h significantly lowered monocytes adherence compared to non-treated HCAECs. NSO and TQ supplementation have anti-atherogenic properties and inhibit monocytes' adherence to HCAECs via down-regulation of ICAM-1 expression. NSO could potentially be incorporated in standard treatment regimens to prevent atherosclerosis and its related complications.

Deletion of the scavenger receptor Scarb1 in myeloid cells does not affect bone mass.

The scavenger receptor class B member 1 (SR-B1 or Scarb1) is a glycosylated cell surface receptor for high density lipoproteins (HDL), oxidized low density lipoproteins (OxLDL), and phosphocholine-containing oxidized phospholipids (PC-OxPLs). Scarb1 is expressed in macrophages and has been shown to have both pro- and anti-atherogenic properties. It has been reported that global deletion of Scarb1 in mice leads to either high or low bone mass and that PC-OxPLs decrease osteoblastogenesis and increase osteoclastogenesis. PC-OxPLs decrease bone mass in 6-month-old mice and are critical pathogenetic factors in the bone loss caused by high fat diet or aging. We have investigated here whether Scarb1 expression in myeloid cells affects bone mass and whether PC-OxPLs exert their anti-osteogenic effects via activation of Scarb1 in macrophages. To this end, we generated mice with deletion of Scarb1 in LysM-Cre expressing cells and found that lack of Scarb1 did not affect bone mass in vivo. These results indicate that Scarb1 expression in cells of the myeloid/osteoclast lineage does not contribute to bone homeostasis. Based on this evidence, and earlier studies of ours showing that Scarb1 expression in osteoblasts does not affect bone mass, we conclude that Scarb1 is not an important mediator of the adverse effects on PC-OxPLs in osteoclasts or osteoblasts in 6-month-old mice.

Hypolipidemic and Anti-Atherogenic Effects of Sesamol and Possible Mechanisms of Action: A Comprehensive Review.

Sesamol is a phenolic lignan isolated from Sesamum indicum seeds and sesame oil. Numerous studies have reported that sesamol exhibits lipid-lowering and anti-atherogenic properties. The lipid-lowering effects of sesamol are evidenced by its effects on serum lipid levels, which have been attributed to its potential for significantly influencing molecular processes involved in fatty acid synthesis and oxidation as well as cholesterol metabolism. In this review, we present a comprehensive summary of the reported hypolipidemic effects of sesamol, observed in several in vivo and in vitro studies. The effects of sesamol on serum lipid profiles are thoroughly addressed and evaluated. Studies highlighting the ability of sesamol to inhibit fatty acid synthesis, stimulate fatty acid oxidation, enhance cholesterol metabolism, and modulate macrophage cholesterol efflux are outlined. Additionally, the possible molecular pathways underlying the cholesterol-lowering effects of sesamol are presented. Findings reveal that the anti-hyperlipidemic effects of sesamol are achieved, at least in part, by targeting liver X receptor α (LXRα), sterol regulatory element binding protein-1 (SREBP-1), and fatty acid synthase (FAS) expression, as well as peroxisome proliferator-activated receptor α (PPARα) and AMP activated protein kinase (AMPK) signaling pathways. A detailed understanding of the molecular mechanisms underlying the anti-hyperlipidemic potential of sesamol is necessary to assess the possibility of utilizing sesamol as an alternative natural therapeutic agent with potent hypolipidemic and anti-atherogenic properties. Research into the optimal sesamol dosage that may bring about such favorable hypolipidemic effects should be further investigated, most importantly in humans, to ensure maximal therapeutic benefit.

Can Electronegative LDL Act as a Multienzymatic Complex?

Electronegative LDL (LDL(-)) is a minor form of LDL present in blood for which proportions are increased in pathologies with increased cardiovascular risk. In vitro studies have shown that LDL(-) presents pro-atherogenic properties, including a high susceptibility to aggregation, the ability to induce inflammation and apoptosis, and increased binding to arterial proteoglycans; however, it also shows some anti-atherogenic properties, which suggest a role in controlling the atherosclerotic process. One of the distinctive features of LDL(-) is that it has enzymatic activities with the ability to degrade different lipids. For example, LDL(-) transports platelet-activating factor acetylhydrolase (PAF-AH), which degrades oxidized phospholipids. In addition, two other enzymatic activities are exhibited by LDL(-). The first is type C phospholipase activity, which degrades both lysophosphatidylcholine (LysoPLC-like activity) and sphingomyelin (SMase-like activity). The second is ceramidase activity (CDase-like). Based on the complementarity of the products and substrates of these different activities, this review speculates on the possibility that LDL(-) may act as a sort of multienzymatic complex in which these enzymatic activities exert a concerted action. We hypothesize that LysoPLC/SMase and CDase activities could be generated by conformational changes in apoB-100 and that both activities occur in proximity to PAF-AH, making it feasible to discern a coordinated action among them.

Nobiletin Improves D-Galactose-Induced Aging Mice Skeletal Muscle Atrophy by Regulating Protein Homeostasis.

Sarcopenia, a decrease in skeletal muscle mass and function caused by aging, impairs mobility, raises the risk of fractures, diabetes, and other illnesses, and severely affects a senior's quality of life. Nobiletin (Nob), polymethoxyl flavonoid, has various biological effects, such as anti-diabetic, anti-atherogenic, anti-inflammatory, anti-oxidative, and anti-tumor properties. In this investigation, we hypothesized that Nob potentially regulates protein homeostasis to prevent and treat sarcopenia. To investigate whether Nob could block skeletal muscle atrophy and elucidate its underlying molecular mechanism, we used the D-galactose-induced (D-gal-induced) C57BL/6J mice for 10 weeks to establish a skeletal muscle atrophy model. The findings demonstrated that Nob increased body weight, hindlimb muscle mass, lean mass and improved the function of skeletal muscle in D-gal-induced aging mice. Nob improved myofiber sizes and increased skeletal muscle main proteins composition in D-gal-induced aging mice. Notably, Nob activated mTOR/Akt signaling to increase protein synthesis and inhibited FOXO3a-MAFbx/MuRF1 pathway and inflammatory cytokines, thereby reducing protein degradation in D-gal-induced aging mice. In conclusion, Nob attenuated D-gal-induced skeletal muscle atrophy. It is a promising candidate for preventing and treating age-associated atrophy of skeletal muscles.

Relationship Between Phenolic Content Determined by LC/MS/MS and Antioxidant Capacity and Enzyme Inhibition of Cyclotrichium niveum L.

Cyclotrichium niveum (Boiss.) Manden & Scheng belonging to the Lamiaceae family, which is an endemic species in the eastern Anatolian region of Turkey, has an important place in terms of ethno-botany. The phytochemical composition of the plant, inhibition of acetylcholinesterase (AChE) (which hydrolyzes the neurotransmitter acetylcholine), inhibition of paraoxonase for antiatherosclerotic activity (hPON 1) (which detoxifies organophosphates), and antioxidant capacity were all investigated in this study. Phytochemical content was determined by LC/MS/MS, and enzyme inhibition and antioxidant capacity studies were determined by spectrophotometer. Antioxidant capacity of C. niveum extracts (methanol, hexane, and water) was determined by applying ABTS⋅+ , DPPH⋅, FRAP, and CUPRAC methods. Both the water and the methanol extracts of the C. niveum exhibited significant inhibition on the AChE (IC50 value for methanol and water extract 0.114±0.14 mg/mL (R2:0.997) and 0.178±0.12 mg/mL (R2 : 0.994), respectively). In contrast, the methanol and water extracts of the C. niveum did not exhibit the inhibition effect on hPON 1. The highest activity for ABTS⋅+ was 66.53 % in the water extract, and DPPH⋅ was 55.03 % in the methanol extract. In the metal-reducing power assay, the absorbance was 0.168±0.04 for FRAP water extract and 0.621±0.01 for CUPRAC methanol extract. According to LC/MS/MS analyses, hydroxybenzoic acid, salicylic acid, syringic acid, acetohydroxamic acid and luteolin determined in the plant extract. As a consequence, C. niveum which has antioxidant, anti-atherogenic and anti-neurodegenerative properties has the potential to be used as a natural medication instead of synthetic drugs used in Alzheimer's patients.

PCSK9 Inhibitors Reduce PCSK9 and Early Atherogenic Biomarkers in Stimulated Human Coronary Artery Endothelial Cells

Despite reports on the efficacy of proprotein convertase subtilisin-Kexin type 9 (PCSK9) inhibitors as a potent lipid-lowering agent in various large-scale clinical trials, the anti-atherogenic properties of PCSK9 inhibitors in reducing PCSK9 and atherogenesis biomarkers via the NF-ĸB and eNOS pathway has yet to be established. This study aimed to investigate the effects of PCSK9 inhibitors on PCSK9, targeted early atherogenesis biomarkers, and monocyte binding in stimulated human coronary artery endothelial cells (HCAEC). HCAEC were stimulated with lipopolysaccharides (LPS) and incubated with evolocumab and alirocumab. The protein and gene expression of PCSK9, interleukin-6 (IL-6), E-selectin, intercellular adhesion molecule 1 (ICAM-1), nuclear factor kappa B (NF-ĸB) p65, and endothelial nitric oxide synthase (eNOS) were measured using ELISA and QuantiGene plex, respectively. The binding of U937 monocytes to endothelial cell capacity was measured by the Rose Bengal method. The anti-atherogenic effects of evolocumab and alirocumab were contributed to by the downregulation of PCSK9, early atherogenesis biomarkers, and the significant inhibition of monocyte adhesion to the endothelial cells via the NF-ĸB and eNOS pathways. These suggest the beyond cholesterol-lowering beneficial effects of PCSK9 inhibitors in impeding atherogenesis during the initial phase of atherosclerotic plaque development, hence their potential role in preventing atherosclerosis-related complications.

Abstract MP03: Adiponectin Levels in Young Adulthood and the Association With Midlife Cognition: The Bogalusa Heart Study

Objective: Adiponectin (ApN), has anti-inflammatory and anti-atherogenic properties. Low levels of ApN are found even after normalization of glucose in patients with diabetes, and are implicated in atherosclerosis, and dementia onset but results vary across the lifespan. We assessed the relation of ApN levels in young adulthood, with midlife atherosclerosis, measured by carotid intima media thickness (cIMT), and with cognitive function among Black and White individuals from the Bogalusa Heart Study (BHS). Methods: A total of 604 participants from the BHS, a community cohort in rural Louisiana, were examined for ApN levels with lowest quartile of ApN levels (<5.4 μg/mL) defined as low-ApN. Structural equation models assessed mediation via the temporal association of low-ApN (age 36±4) with midlife (age 49±5) cIMT, dichotomized above the 50 th percentile (>0.88mm), and a global cognitive score(GCS) standardized for age, race and sex. Adjusted models included education attendance. Results: Individuals with low-ApN were more likely men [ 56.2% (77), p<0.001] and White [54.7% (75), p<0.001]. No differences in education were found. There was a direct association between low-ApN and GCS (P=0.025), low-ApN and cIMT ≥ 50 th (P=0.001), and cIMT ≥ 50 th and GCS (P=0.002). ( Figure1) In mediation analysis, the ratio of Indirect effect/Total effect was 0.108, indicating that ~11% of the effect of low-ApN on GCS was mediated by cIMT. Education was not associated with low-ApN. Conclusion: Low-ApN levels in early adulthood was associated with poor cognition after ~10 years of follow-up, and the association was partially mediated by subclinical atherosclerosis. This suggests that ApN may play a role in neurodegeneration mechanisms and contribute to the development of dementia, underscoring the importance of addressing cardiometabolic influences earlier in the lifespan to prevent/delay cognitive decline.

Adding Modified Buckwheat Sprouts to an Atherogenic Diet — the Effect on Selected Nutritional Parameters in Rats

The germinated seeds of many plants are a natural source of substances that can be used to supplement food and increase its functionality. The seeds’ metabolism may be modified during germination to produce specific health-promoting compounds. Fagopyrum esculentum Moench is a rich source of nutrients. Buckwheat seeds modified during germination may be helpful as an additive to new functional food products with anti-atherogenic properties. However, their effect and safety should be assessed in in vivo studies. The aim of the study was to evaluate the effect that adding modified buckwheat sprouts (Fagopyrum esculentum Moench) to an atherogenic (high-fat) diet has on the morphology and digestibility parameters of rats. Buckwheat seeds were modified by adding the probiotic strain of the yeast Saccharomyces cerevisiae var. boulardii. The study was carried out on 32 Wistar rats, and digestibility and blood counts were assessed during the experiment. There was no evidence of an adverse effect on the animals' weight gain and nutritional efficiency. However, the influence of diets with freeze-dried buckwheat sprouts on digestibility and morphological parameters was noticed. Fat digestibility registered a statistically significant decrease in the groups fed a high-fat diet with the addition of sprouts. The study shows a new direction in the use of buckwheat sprouts.

Glucagon-Like Peptide 1 Receptor Agonists Versus Sodium-Glucose Cotransporter 2 Inhibitors for Atherosclerotic Cardiovascular Disease in Patients With Type 2 Diabetes.

Beyond improving hemoglobin A1c (HbA1c) in adults with type 2 diabetes, glucagon-like peptide 1 receptor agonists (GLP-1RA) have been approved for reducing risk of major adverse cardiovascular events (MACE) with established cardiovascular disease (CVD) or multiple CV risk factors. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) also reduced the risk for the primary composite CV outcome in patients with type 2 diabetes at high risk for CV events. In the American Diabetes Association (ADA) and European Association of Study in Diabetes (EASD) consensus report 2022, there is the description "In people with established atherosclerotic CVD (ASCVD) or with a high risk for ASCVD, GLP-1RA were prioritized over SGLT2i"; however, the evidence supporting such statement is limited. Therefore, we studied the superiority of GLP-1RA over SGLT2i for prevention of ASCVD from various viewpoints. We could not find a meaningful difference in the risk reduction in three-point MACE (3P-MACE), mortality due to any cause, mortality due to CV cause and nonfatal myocardial infarction between GLP-1RA and SGLT2i trials. The risk of nonfatal stroke decreased in all five GLP-1RA trials; however, two of three SGLT2i trials showed an increase in risk of nonfatal stroke. The risk of hospitalization for heart failure (HHF) decreased in all three SGLT2i trials, and one GLP-1RA trial showed an increase in risk of HHF. The risk reduction of HHF in SGLT2i trials was greater than that in GLP-1RA trials. These findings were consistent with current systematic reviews and meta-analyses. The risk reduction of 3P-MACE was significantly and negatively correlated with changes in HbA1c (R = -0.861, P = 0.006) and body weight (R = -0.895, P = 0.003) in GLP-1RA and SGLT2i trials. The studies using SGLT2i failed to reduce carotid intima media thickness (cIMT), the surrogate marker for atherosclerosis; however, several studies using GLP-1RA successfully reduced cIMT in patients with type 2 diabetes. Compared with SGLT2i, GLP-1RA had a higher probability of decreasing serum triglyceride. GLP-1RA have multiple vascular biological anti-atherogenic properties.

Effect of Berberis vulgaris fruit powder on visfatin and metabolic profiles in type 2 diabetes mellitus patients: A randomized, double-blind, placebo-controlled trial

BackgroundType 2 diabetes mellitus (T2DM) is a multifactorial disorder that is strongly associated with cardiovascular complications. Berberis vulgaris (B. vulgaris) is a traditional plant with anti-diabetic and anti-atherogenic properties. The present study aimed to investigate the effect of B. vulgaris on visfatin and metabolic profiles in T2DM. MethodsIn this double-blind clinical trial, 40 patients with T2DM were randomized into two equal groups: i) 1000 mg B. vulgaris was administered at a dosage of 2 × 500 mg capsules daily (BFP group), ii) placebo was administered as 500 mg capsules containing lactose twice a day (PL group) for 8 weeks. Anthropometric parameters, biochemical tests and serum visfatin levels were measured prior to and following the intervention. ResultsThe changes in the Total Cholesterol (P = 0.006), Triglyceride (TG) (P = 0.001), High-Density Lipoprotein-Cholesterol (HDL-C) (P = 0.001), Low-Density Lipoprotein-Cholesterol (LDL-C) (P = 0.004), LDL-C/HDL-C (P = 0.001), TG/HDL-C (P = 0.001) and, Total Cholesterol/HDL-C (P = 0.009) between the two groups was significant at the end of trial. Moreover, visfatin was significantly changed following 8-weeks in the group receiving B.Vulgaris in comparison with the PL group (P = 0.01), based on ANCOVA. ConclusionsB. vulgaris supplementation appears to have favorable effects on lipid profile and serum visfatin in T2DM.