Effect of Heat-Treated Garlic (Allium sativum L.) on Growth Parameters, Plasma Lipid Profile and Histological Changes in the Ileum of Atherogenic Rats.

Dietary supplementation with raw garlic has a preventive and healing effect in cardiovascular diseases, but it could also damage the intestinal mucosa, resulting in impairment of nutrient absorption. Garlic processing, including heat treatment, changes the content and biological activity of garlic, so it is crucial to find food-processing methods that will preserve the health-promoting properties of garlic while minimizing its negative impact on the digestive system. Therefore, in this study, the effect of garlic (Allium sativum L.) on growth parameters, plasma lipid profile, and morphological parameters in the ileum of Wistar rats subjected to various types of heat treatment (90 s blanching garlic, 10 min boiling in water, 10 min pan frying without fat, microwave heating fresh garlic, 90 s blanching and microwave heating garlic, 10 min boiling in water and microwave heating garlic, and 10 min pan frying without fat and microwave heating garlic) was determined in an atherogenic diet (containing 1% addition of cholesterol). In the conducted research, it was found that the diet supplemented with heat-treated garlic used in the atherogenic diet improved the consumption and growth parameters of rats, depending on the type and time of its use. The highest consumption was recorded in atherogenic groups supplemented with garlic subjected to a longer (10 min) heat treatment and was then heated in a microwave oven. Garlic subjected to the shortest heat treatment proved to be most effective, and a significant improvement in the lipid profiles of rats' plasma with atherogenic was observed. Extending the time of heat treatment of garlic and, additionally, its microwaving significantly weakened the action of garlic in the body, but still retained its hypolipidemic effect. The greatest influence on the structural changes in the mucosa of the rats' iliac intestine, manifested by degeneration of the mucosa, shortening the length of the intestinal villi, damage to the brush border, and thus impairment of the intestinal absorption, was exerted by supplementing the atherogenic diet with garlic subjected to short-term heat treatment. Among the processes used, blanching was the least favorable, and the long-lasting thermal processes (cooking, frying for 10 min) had a positive effect on the mucosa of the rats' intestines. The results obtained in this study confirm that the selection of an appropriate method of thermal processing of garlic may allow for the maintenance of preventive and therapeutic efficacy of garlic in cardiovascular diseases, while ensuring the safety of its long-term use in the context of degenerative changes in the gastrointestinal tract.

Effect of Dietary or Supplemental Vitamin C Intake on Vitamin C Levels in Patients with and without Cardiovascular Disease: A Systematic Review.

Atherosclerosis is a pro-oxidative and pro-inflammatory disease state, which is the underlying cause of most cardiovascular events, estimated to affect 5.2% of the Australian population. Diet, and specifically vitamin C, through its antioxidant properties can play a role in impeding the development and progression of atherosclerosis. This systematic review conducted comprehensive searches in Medline, Emcare, Scopus, PubMed, and Cochrane using key search terms for vitamin C, plasma vitamin C, supplementation, and cardiovascular disease (CVD). The results demonstrated that vitamin C supplementation resulted in a significant increase in vitamin C levels in populations with or without CVD, except for one study on the CVD population. It was also seen that the healthy population baseline and post-intervention vitamin C levels were high compared to the CVD population. However, further research is indicated for CVD population groups with varying baseline vitamin C levels, such as low baseline vitamin C, within a more representative elderly cohort in order to formulate and update vitamin C repletion guidelines.

Thymoquinone, a major constituent in Nigella sativa seeds, is a potential preventative and treatment option for atherosclerosis.

Atherosclerosis is a widespread and progressive chronic arterial disease that remains the leading cause of mortality and morbidity worldwide. It is generally accepted that atherosclerosis is a multifactorial disease characterized by dyslipidemia and inflammation in the vessel walls. Nonpharmacological interventions to treat chronic diseases like atherosclerosis have gained considerable attention in recent years. Thymoquinone (TQ), the major bioactive constituent of Nigella sativa seeds, presents one such example of a natural therapeutic agent that has captured the attention of many researchers due to its wide array of medicinal properties, including its potent anti-atherosclerotic effects. Various in vitro and in vivo studies support the potential of TQ in ameliorating hyperlipidemia, hypercholesterolemia, oxidative stress, and inflammation, all of which are key hallmarks of atherosclerosis. However, to date, no review has been conducted to substantiate the role of TQ in preventing and/or treating atherosclerosis. This comprehensive review aims to examine recent in vitro and in vivo experimental findings reported on the potential anti-atherosclerotic effects of TQ. The roles of TQ in combatting hyperlipidemia, oxidative stress, and inflammation in atherosclerosis are highlighted. We also shed light on the role of TQ in preventing foam cell formation by decreasing low-density lipoprotein (LDL) availability and oxidation. Moreover, recent findings on the protective role of TQ on early markers of atherosclerosis, including homocysteinemia and endothelial dysfunction, are also underscored. Experimental evidence suggests that TQ can potentially be employed as a natural therapeutic agent with minimal side effects against the development and/or progression of atherosclerosis and its associated complications.

Dietary iron overload mitigates atherosclerosis in high-fat diet-fed apolipoprotein E knockout mice: Role of dysregulated hepatic fatty acid metabolism.

The atherosclerosis "iron hypothesis" generates a fair amount of debate since it has been proposed. Here, we revisited the "iron hypothesis" by examining whether dietary iron overload would intensify iron deposition in plaques and thus lead to further exacerbation of atherosclerosis in apolipoprotein E knockout (ApoE KO) mice. ApoE KO mice were fed either a normal chow diet (ND) or a high fat diet (HFD) supplemented with or without 2% carbonyl iron (Fe) for 16 weeks. However, contrary to our assumption, dietary iron overloading did not intensify, but rather diminished the atherosclerotic lesion area by 65.3%, which was accompanied by significantly decreased serum total cholesterol, triglyceride and low-density lipoprotein cholesterol contents, together with hepatic lipid accumulation decline, despite the evident existence of aortic iron accumulation and the typical signs of iron overload in ApoE KO mice. Using isobaric tag for absolute quantification (iTRAQ) proteomics approach, hepatic CD36 and fatty acid binding proteins-mediated fatty acid (FA) uptake and trafficking impairment were identified as the key potential pathomechanisms by which iron overload diminishes atherosclerotic lesions. Furthermore, downstream hepatic FA de novo biosynthesis was enhanced and FA oxidation was inhibited to compensate for the FA deficiency triggered by iron overload-impaired fatty acid uptake and trafficking. Our findings suggested that dietary iron overload is not atherogenic in ApoE KO mice, and more research efforts are warranted to revisit the "iron hypothesis" of atherosclerosis.

Triglyceride-lowering and anti-inflammatory mechanisms of omega-3 polyunsaturated fatty acids for atherosclerotic cardiovascular risk reduction.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death globally. Omega-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid and docosahexaenoic acid have been extensively studied as both dietary supplement and pharmaceutical agent for the prevention of ASCVD. Epidemiological and retrospective studies have long shown the inverse relationship of omega-3 PUFA consumption and ASCVD event but results of previous large randomized controlled trials have not consistently shown the same effect. Meta-analysis and a recent clinical trial using a high dose of eicosapentaenoic acid showed convincing protective effects of omega-3 PUFAs on ASCVD. Emerging evidence shows that both chronic inflammation and hypertriglyceridemia increase the risk of atherosclerosis. Amelioration of the inflammatory process and reduction of hypertriglyceridemia provide two mechanisms on the prevention and management of ASCVD, and agents with both of these effects are more potent and desirable. Omega-3 PUFAs exert anti-hypertriglyceridemia effect, ameliorate inflammation, and maintain the resolution of inflammation homeostasis pleiotropically through multiple molecular and cellular mechanisms. This review presents the pathophysiology of atherosclerosis, the mechanisms of omega-3 PUFAs on the reduction of the atherosclerotic risk, and the current clinical utilities of omega-3 PUFAs on the prevention of ASCVD.

12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice.

Atherosclerosis is a chronic inflammatory disease associated with macrophage aggregate and transformation into foam cells. In this study, we sought to investigate the impact of dietary intake of ω3 fatty acid on the development of atherosclerosis, and demonstrate the mechanism of action by identifying anti-inflammatory lipid metabolite. Mice were exposed to a high-fat diet (HFD) supplemented with either conventional soybean oil or α-linolenic acid-rich linseed oil. We found that as mice became obese they also showed increased pulsatility and resistive indexes in the common carotid artery. In sharp contrast, the addition of linseed oil to the HFD improved pulsatility and resistive indexes without affecting weight gain. Histological analysis revealed that dietary linseed oil inhibited foam cell formation in the aortic valve. Lipidomic analysis demonstrated a particularly marked increase in the eicosapentaenoic acid-derived metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) in the serum from mice fed with linseed oil. When we gave 12-HEPE to mice with HFD, the pulsatility and resistive indexes was improved. Indeed, 12-HEPE inhibited the foamy transformation of macrophages in a peroxisome proliferator-activated receptor (PPAR)γ-dependent manner. These results demonstrate that the 12-HEPE-PPARγ axis ameliorates the pathogenesis of atherosclerosis by inhibiting foam cell formation.

Investigating the mechanisms of Modified Xiaoyaosan (tiaogan-liqi prescription) in suppressing the progression of atherosclerosis, by means of integrative pharmacology and experimental validation.

Atherosclerosis (AS)-related diseases remain among the leading causes of death worldwide. Modified Xiaoyaosan (also called Tiaogan-Liqi prescription, TGLQ), a traditional Chinese medical formulation, has been widely applied in the treatment of AS-related diseases. The aim of this study was to investigate the underlying pharmacological mechanisms of TGLQ in acting on AS. A total of 548 chemical compounds contained in TGLQ, and 969 putative targets, were collected from the Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine, while 1005 therapeutic targets for the treatment of AS were obtained from the DisGeNET, TTD and CTD databases. Moreover, the 63 key targets were screened by the intersection of the targets above, and by network topological analysis. Further functional enrichment analysis showed that the key targets were significantly associated with regulation of the immune system and inflammation, improvement of lipid and glucose metabolism, regulation of the neuroendocrine system and anti-thrombosis effect. The in vivo experiments confirmed that TGLQ could reduce plasma lipid profiles and plasma inflammatory cytokines, and also inhibit AS plaque formation, within the AS model ApoE-/- mice. The in vitro experiments validated the hypothesis that TGLQ could significantly reduce intracellular lipid accumulation, suppress the production of inflammatory cytokines of macrophages induced by oxidized-LDL, and inhibit the protein expression of heat shock protein 90 and toll-like receptor 4. This study identified a list of key targets of TGLQ in the treatment of AS by applying an integrative pharmacology approach, which was validated by in vivo and in vitro experimentation.

Synergistic effect of Betulinic acid, Apigenin and Skimmianine (BASk) in high cholesterol diet rabbit: Involvement of CD36-TLR2 signaling pathway.

BACKGROUND: Progression of chronic inflammatory disease, atherosclerosis is a multifactorial process. Cluster of differentiation 36 (CD36) mediated downstream activation of Toll like receptor 2 (TLR2) and NLRP3 (Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome signaling pathway actively participates during chronic inflammation. Nowadays, synergistic combinations of bioactive compounds attained priority in the field of drug discovery and development as therapeutic agents. An investigation regarding the anti-inflammatory potential of a novel drug formulation, BASk which is a combination of three bioactive compounds Betulinic acid (B):Apigenin (A):Skimmianine (Sk) remains the focus area of this research study. We also elucidate the molecular mechanism behind the therapeutic potential of BASk through CD36 mediated activation TLR2-NLRP3 signaling pathway. METHODS: OxLDL induced hPBMCs used to screen out a suitable combination of BASk via MTT, COX, LOX, NOS and MPO assays. Hypercholesterolemia is induced in rabbits by supplementing with 1% cholesterol + 0.5% cholic acid and treated with BASk (2:2:1) (5 mg/Kg) and atorvastatin (10 mg/Kg) for 60 days. CD36, TLR2, NLRP3, NFκB, cytokines, endothelial damage were quantified by reverse transcription, real time PCR, ELISA, flow cytometry and histopathology. RESULTS: hPBMCs pretreated with BASk at 2:2:1 ratio significantly decreased the activities of COX, 15-LOX, NOS and MPO on OxLDL induction than quercetin. Down regulation of CD36, TLR2, MyD88, TRAF6 by BASk further buttressed NLRP3 inflammasome activation mediated by the transcription factor NFκB. This is in correlation with the effect of BASk by balancing pro (IL-1ß, IL-18) and anti-inflammatory (TGF-ß) mediators in the aortic endothelial cells. CONCLUSION: BASk exerted its anti-inflammatory potential by reducing pro-inflammatory mediators during cholesterol supplementation via down regulating CD36 mediated TLR2 - NLRP3 inflammasome cascade. This deciphers a synergistic combination named BASk (2:2:1) as a novel drug formulation against chronic inflammatory disease, atherosclerosis.

Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (Bifidobacterium longum BB536, Red Yeast Rice Extract) (Randomized, Double-Blind, Placebo-Controlled Study).

BACKGROUND: Oxysterol relationship with cardiovascular (CV) risk factors is poorly explored, especially in moderately hypercholesterolaemic subjects. Moreover, the impact of nutraceuticals controlling hypercholesterolaemia on plasma levels of 24-, 25- and 27-hydroxycholesterol (24-OHC, 25-OHC, 27-OHC) is unknown. METHODS: Subjects (n = 33; 18-70 years) with moderate hypercholesterolaemia (low-density lipoprotein cholesterol (LDL-C:): 130-200 mg/dL), in primary CV prevention as well as low CV risk were studied cross-sectionally. Moreover, they were evaluated after treatment with a nutraceutical combination (Bifidobacterium longum BB536, red yeast rice extract (10 mg/dose monacolin K)), following a double-blind, randomized, placebo-controlled design. We evaluated 24-OHC, 25-OHC and 27-OHC levels by gas chromatography/mass spectrometry analysis. RESULTS: 24-OHC and 25-OHC were significantly correlated, 24-OHC was correlated with apoB. 27-OHC and 27-OHC/total cholesterol (TC) were higher in men (median 209 ng/mL and 77 ng/mg, respectively) vs. women (median 168 ng/mL and 56 ng/mg, respectively); 27-OHC/TC was significantly correlated with abdominal circumference, visceral fat and, negatively, with high-density lipoprotein cholesterol (HDL-C). Triglycerides were significantly correlated with 24-OHC, 25-OHC and 27-OHC and with 24-OHC/TC and 25-OHC/TC. After intervention, 27-OHC levels were significantly reduced by 10.4% in the nutraceutical group Levels of 24-OHC, 24-OHC/TC, 25-OHC, 25-OHC/TC and 27-OHC/TC were unchanged. CONCLUSIONS: In this study, conducted in moderate hypercholesterolemic subjects, we observed novel relationships between 24-OHC, 25-OHC and 27-OHC and CV risk biomarkers. In addition, no adverse changes of OHC levels upon nutraceutical treatment were found.

Clearing the Clutter: Antiatherosclerotic activity of Eucalyptus camaldulensis crude extract.

Plant components have been extensively evaluated for their pharmacological activities. This study provides scientific rationale towards the therapeutic effect of Eucalyptus camaldulensis aqueous bark extract against induced atherosclerosis and hyperlipidemia in pigeons. Phytochemical components of Eucalyptus bark extract possess a great antioxidant activity that potentially reduced the risk of heart diseases. A total of 42 Pigeons of both sexes were distributed into negative control (fed normal grain diet), hyperlipidemic control (fed HFD 1% animal fat oil and 0.1% cholesterol for 3 months), test groups of variable doses (0.05, 0.1, 0.2 to 0.4 gms/kg BW for 21 days) and the group received atorvastatin daily after induction used. At the end of the experiment biochemical and histological evaluation has been performed. After HFD induction the serum levels of liver enzyme AST, glucose, urea, cholesterol, LDL, VLDL, and TG were significantly increased with the reduction in HDL levels. The atherogenic index was also found significantly raised. Microscopic examination of the liver and aorta showed the appearance of lipid-filled foam cells all over the liver parenchyma and intima after the HFD induction. Thus it was concluded that Eucalyptus aqueous bark extract can be effective against atherosclerosis and hyperlipidemia.

Anti-atherogenic properties of Kgengwe (Citrullus lanatus) seed powder in low-density lipoprotein receptor knockout mice are mediated through beneficial alterations in inflammatory pathways.

Kgengwe fruits are commonly consumed in sub-Saharan countries. Recent reports indicated low coronary artery disease rates in those regions. To investigate anti-atherogenic properties and potential mechanisms of action of Kgengwe seed powder (KSP), male low-density lipoprotein receptor knockout (LDL-r-KO) mice were fed with an atherogenic diet supplemented with (treated, n = 10) or without (controls, n = 10) 10% (w/w) KSP for 20 weeks. Proximate analysis revealed that KSP contained 38% fibre and 15% lipids. KSP supplementation was not associated with significant changes in body weight gain rate, food intake, and plasma lipid levels. However, the average atherosclerotic lesion size in the aortic roots in the KSP-treated group was 58% smaller than that in the control group (0.26 vs 0.11 mm2, p < 0.05). This strong anti-atherogenic effect was associated with significant increases in the average plasma levels of certain cytokines such as IL-10 (6 vs 13 pg/mL, p < 0.05), GM-CSF (0.1 vs 0.2 pg/mL, p < 0.05), and EPO (7 vs 16 pg/mL, p < 0.05) along with reductions in the average levels of plasma MCP-1 (19 vs 14 pg/mL, p < 0.05) and MIP-2 (28 vs 13 pg/mL, p < 0.05). Except for relatively high levels of saturated fatty acids, KSP possesses balanced nutrient compositions with strong anti-atherogenic properties, which may be mediated through alterations in inflammatory pathways. Additional studies warrant confirmation and mechanism(s) of action of such effects. Novelty: Kgengwe seeds prevent atherogenesis in LDL-r-KO mice. Kgengwe seeds increase circulating levels of IL-10 and EPO. No reduction in plasma total cholesterol levels.

Integrating systematic biological and proteomics strategies to explore the pharmacological mechanism of danshen yin modified on atherosclerosis.

This research utilized the systematic biological and proteomics strategies to explore the regulatory mechanism of Danshen Yin Modified (DSYM) on atherosclerosis (AS) biological network. The traditional Chinese medicine database and HPLC was used to find the active compounds of DSYM, Pharmmapper database was used to predict potential targets, and OMIM database and GeneCards database were used to collect AS targets. String database was utilized to obtain the other protein of proteomics proteins and the protein-protein interaction (PPI) data of DSYM targets, AS genes, proteomics proteins and other proteins. The Cytoscape 3.7.1 software was utilized to construct and analyse the network. The DAVID database is used to discover the biological processes and signalling pathways that these proteins aggregate. Finally, animal experiments and proteomics analysis were used to further verify the prediction results. The results showed that 140 active compounds, 405 DSYM targets and 590 AS genes were obtained, and 51 differentially expressed proteins were identified in the DSYM-treated ApoE-/- mouse AS model. A total of 4 major networks and a number of their derivative networks were constructed and analysed. The prediction results showed that DSYM can regulate AS-related biological processes and signalling pathways. Animal experiments have also shown that DSYM has a therapeutic effect on ApoE-/-mouse AS model (P < .05). Therefore, this study proposed a new method based on systems biology, proteomics, and experimental pharmacology, and analysed the pharmacological mechanism of DSYM. DSYM may achieve therapeutic effects by regulating AS-related signalling pathways and biological processes found in this research.

Gypenoside Inhibits Endothelial Cell Apoptosis in Atherosclerosis by Modulating Mitochondria through PI3K/Akt/Bad Pathway.

Atherosclerosis remains the most common cause of deaths worldwide. Endothelial cell apoptosis is an important process in the progress of atherosclerosis, as it can cause the endothelium to lose their capability in regulating the lipid homeostasis, inflammation, and immunity. Endothelial cell injury can disrupt the integrity and barrier function of an endothelium and facilitate lipid deposition, leading to atherogenesis. Chinese medicine techniques for preventing and treating atherosclerosis are gaining attention, especially natural products. In this study, we demonstrated that gypenoside could decrease the levels of serum lipid, alleviate the formation of atherosclerotic plaque, and lessen aortic intima thickening. Gypenoside potentially activates the PI3K/Akt/Bad signal pathway to modulate the apoptosis-related protein expression in the aorta. Moreover, gypenoside downregulated mitochondrial fission and fusion proteins, mitochondrial energy-related proteins in the mouse aorta. In conclusion, this study demonstrated a new function of gypenoside in endothelial apoptosis and suggested a therapeutic potential of gypenoside in atherosclerosis associated with apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway.

Improvement of Endothelial Dysfunction of Berberine in Atherosclerotic Mice and Mechanism Exploring through TMT-Based Proteomics.

Atherosclerosis is a multifactorial vascular disease triggered by disordered lipid metabolism, characterized by chronic inflammatory injury, and initiated by endothelial dysfunction. Berberine is the main active alkaloid of the herbal medicine Coptidis Rhizoma (Huanglian). Notably, berberine has been shown to have beneficial effects against atherosclerosis. However, the mechanisms of berberine in preventing atherosclerosis are still unclear. This study is aimed at investigating the effects and mechanisms of berberine in protecting the aorta and ameliorating atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. Here, we demonstrated that berberine reduced serum lipid levels, antagonized hepatic lipid accumulation, improved intima-media thickening, and alleviated atherosclerotic lesions in ApoE-/- mice fed a western-type diet for 12 weeks. Meanwhile, berberine reduced aortic reactive oxygen species (ROS) generation and reduced the serum levels of malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), and interleukin-6 (IL-6). In aortic ring assay, berberine restored aortic endothelium-dependent vasodilatation in vivo and in vitro. Furthermore, 4,956 proteins were identified by proteomic analysis, and 199 differentially expressed proteins regulated by berberine were found to be involved in many biological pathways, such as mitochondrial dysfunction, fatty acid ß-oxidation I, and FXR/RXR activation. Summarily, these data suggested that berberine ameliorates endothelial dysfunction and protects against atherosclerosis, and thus may be a promising therapeutic candidate for atherosclerosis.

The paradigm of immunosenescence in atherosclerosis-cardiovascular disease (ASCVD).

The new immunosenescence paradigm (2015) was an attempt to explain a mechanism by which macrophages could be immunosuppressed and dysfunctional, yet paradoxically release proinflammatory factors in an unregulated manner. This mechanism was linked to the loss of dehydroepiandrosterone (DHEA) with aging and thus explained how immunosenescence could be causally related to the risk of stress and/or age-associated chronic diseases. At the center of this paradigm was lipid body negative (LB-) foamy macrophage (CD14+CD16+) which produced human endogenous retrovirus K102 (HERV-K102) particles. HERV-K102 may be a protector foamy virus of humans, and its induction may generate trained innate immunity, a special type of autoimmunity, in response to intracellular pathogens, their constituents, toxins, and/or tumors. Overwhelming evidence now suggests that the proinflammatory foamy macrophages driving ASCVD are LB-. Moreover, the monocyte/macrophage phenotype implicated in atherosclerosis-cardiovascular disease (ASCVD) appears to be the CD14+CD16+ intermediate phenotype. These and other observations directly challenge the cholesterol hypothesis. For the prevention and treatment of ASCVD, it is important to address the putative cause of ASCVD -- immunosenescence, rather than the signs or symptoms such as inflammation or elevated cholesterol. Therefore, strategies to reverse or prevent immunosenescence, which improve or maintain an optimal cortisol/DHEA ratio such as isoflavonoids, would be expected to alleviate not only ASCVD but the risk of many other age-associated chronic diseases. Here, the new immunosenescence paradigm will be appraised for its suitability to explain ASCVD risks.

Small dense low-density lipoprotein-lowering agents.

Metabolic disorders, including obesity, diabetes, and hyperlipidemia, as well as cardiovascular diseases (CVD), particularly atherosclerosis, are still leading causes of death worldwide. Plasma levels of low-density lipoprotein (LDL) are currently being considered as a critical risk factor for the diseases mentioned above, especially atherosclerosis. Because of the heterogeneous nature of LDL, many studies have already been conducted on its subclasses, especially small dense LDL (sdLDL). According to available evidence, sdLDL levels can be considered as an ideal alternative to LDL levels for monitoring CVD and early diagnosis of atherosclerosis. Recently, several researchers have focused on factors that are able to decrease sdLDL levels and improve health quality. Therefore, the purpose of this study is to describe the production process of sdLDL particles and review the effects of pharmaceutical and dietary agents as well as lifestyle on sdLDL plasma levels. In brief, their mechanisms of action are discussed. Apparently, cholesterol and LDL-lowering compounds are also effective in the reduction of sdLDL levels. In addition, improving lipid profile, especially the reduction of triglyceride levels, appropriate regimen, and lifestyle can decrease sdLDL levels. Therefore, all the aforementioned parameters should be taken into consideration simultaneously in sdLDL levels reducing strategies.

Dihydromyricetin increases endothelial nitric oxide production and inhibits atherosclerosis through microRNA-21 in apolipoprotein E-deficient mice.

Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata, in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient (Apoe-/- ) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe-/- mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe-/- mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.

Anti-lipidemic Effect of Fractions of Peristrophe bivalvis Leaf in NG-nitro-L-arginine Methyl Ester (L-NAME) Treated Rats.

PURPOSE: The reduction in nitric oxide (NO) bioavailability accelerates atherosclerosis development, augments lipolysis, elevates blood pressure and upregulate leukocyte level. This study was designed to examine the biochemical constituents of fractions of Peristrophe bivalvis (PB) leaf, their effect on blood pressure, serum lipid contents and complete blood count in NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. METHOD: Male Wistar rats were grouped into control and hypertensive groups. The hypertensive group was pretreated with 60 mg/kg b.w of L-NAME (L-NAME60) daily for two weeks. They were then randomly sub-grouped into: Hypertensive (H), Hypertensive+n-hexane fraction (HHF), Hypertensive+dichloromethane fraction (HDF), Hypertensive+ethyl acetate fraction (HEF) and Hypertensive+aqueous fraction (HAF) groups. These were orally gavaged with L-NAME60 and L-NAME60+200 mg/kg b.w of fractions of PB respectively, daily for two weeks. RESULT: The biochemical components analysis of the fractions of PB identified numerous polar and non polar compounds like alkaloids, organic acids and esters. The results showed a significant increase in NO level in HHF and HEF groups compared to H. Total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C) and very LDL-C were significantly decreased in HAF group compared to H. High density lipoprotein cholesterol (HDL-C) increased significantly and atherogenic indices decreased significantly in HHF, HDF and HAF groups compared to H, while reduced glutathione level increased significantly in HHF group compared to H. White blood cells count effectively decreased in HEF group compared to H. CONCLUSION: In brief, the fractions of PB leaf increased HDL-C and NO, and decrease atherogenic indices in L-NAME treated rats.

Anthocyanins in berries exhibited anti-atherogenicity and antiplatelet activities in a metabolic syndrome population.

Metabolic syndrome (MetS) is a global challenge for atherosclerosis. It was hypothesized that a four-week consumption of anthocyanin supplements by MetS patients who had three or more risk factors linked with metabolic syndrome would have a greater improvement in cardiometabolic biomarkers and would also reduce the risk of thrombosis. A total of 55 participants in two groups of Normal healthy and MetS (age 25-75y) were given 320 mg anthocyanin supplements twice daily for 4 weeks. Platelet coagulant activities, lipid profiles, fasting blood glucose, and inflammatory and oxidative stress biomarkers were measured before and after supplementation to evaluate the atheroprotective effects of anthocyanins in the study subjects. Four weeks of anthocyanin supplementation significantly decreased cardiometabolic risk factors including the average serum fasting blood glucose (FBG) (by 13.3%, P < .05) and lipid profiles by significant reduction in triglyceride (by 24.9%, P < .05) and LDL-C (by 33.1%, P < .05) in the MetS group. Anthocyanin supplementation also decreased high sensitivity C-reactive protein (hs-CRP) level (by 28%, P < .05) in females. However, no significant differences in serum UA (uric acid) and HDL-C were observed between anthocyanin pre- and post-treatment in both groups. Moreover, Anthocyanin supplements decreased ADP-induced platelet activation configuration expressed as P-selectin by 40% (P < .05). There was a positive correlation between decreased hs-CRP values and the levels of LDL-C and FBG in the MetS group (P < .05). These results support the hypothesis that anthocyanin supplementation exerts anti-atherogenicity effects by improving cardiometabolic risk factors and reducing thrombogenicity in the MetS population.