Marine Phospholipids from Fishery By-Products Attenuate Atherosclerosis

In this study, the anti-atherosclerotic properties of three marine phospholipids (MPLs) extracts from fishery by-products including codfish roe, squid gonad, and shrimp head are verified. Their effects on key factors involved in atherosclerosis are examined and compared to explore whether the differences in their constitutions lead to the differences in the function. All three MPLs dampen oxidation of low- density lipoproteins (LDL) in vitro. Treating RAW264.7 macrophages and HUVECs endothelial cells with each MPLs ranging 10–100 µg mL⁻¹ does not decrease cell viability, yet ox-LDL caused cytotoxicity of both cells are alleviated by 50 or 100 µg mL⁻¹ MPLs treatment. In addition, the three MPLs reduce ox-LDL induced macrophage foam-like transition, mainly through inhibition of lipid uptake. Of the three MPLs, the one from squid gonad exhibits the best effect. On the other hand, all three MPLs modulate inflammatory responses, equally, by inhibiting the adhesion of monocytes to endothelial cells, and decreasing secretion of pro-inflammatory cytokines IL-6 and MCP-1. Using a high-cholesterol diet induced zebrafish model, it is found that all three MPLs, especially the one from squid gonad, alleviates cholesterol accumulation in early plaques, and decreases total cholesterol as well as lipid peroxide in vivo. Practical Applications: As a way of making the best of the increasingly scarce marine resources, valuable lipid components can be recovered from by-products and wastes from the fishery industry. Here, we tested the anti-atherosclerotic effects and the mechanisms of three MPLs extracted from codfish roe, squid gonad, and shrimp head. Our study provides further evidence that marine phospholipids extracted from fishery by-products could protect against atherosclerosis, and helps to elucidate the structure-function relationship of MPLs.     

Role of Macrophages and RhoA Pathway in Atherosclerosis

The development, progression, or stabilization of the atherosclerotic plaque depends on the pro-inflammatory and anti-inflammatory macrophages. The influx of the macrophages and the regulation of macrophage phenotype, inflammatory or anti-inflammatory, are controlled by the small GTPase RhoA and its downstream effectors. Therefore, macrophages and the components of the RhoA pathway are attractive targets for anti-atherosclerotic therapies, which would inhibit macrophage influx and inflammatory phenotype, maintain an anti-inflammatory environment, and promote tissue remodeling and repair. Here, we discuss the recent findings on the role of macrophages and RhoA pathway in the atherosclerotic plaque formation and resolution and the novel therapeutic approaches.     

Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease

Neutrophils are primary effector cells of innate immunity and fight infection by phagocytosis and degranulation. Activated neutrophils also release neutrophil extracellular traps (NETs) in response to a variety of stimuli. These NETs are net-like complexes composed of cell-free DNA, histones and neutrophil granule proteins. Besides the evolutionarily conserved mechanism to capture and eliminate pathogens, NETs are also associated with pathophysiological processes of various diseases. Here, we elucidate the mechanisms of NET formation and their different implications in disease. We focused on autoinflammatory and cardiovascular disorders as the leading cause of death. Neutrophil extracellular traps are not only present in various cardiovascular diseases but play an essential role in atherosclerotic plaque formation, arterial and venous thrombosis, as well as in the development and progression of abdominal aortic aneurysms. Furthermore, NETosis can be considered as a source of autoantigens and maintains an inflammatory milieu promoting autoimmune diseases. Indeed, there is further need for research into the balance between NET induction, inhibition, and degradation in order to pharmacologically target NETs and their compounds without impairing the patient’s immune defense. This review may be of interest to both basic scientists and clinicians to stimulate translational research and innovative clinical approaches.     

Modified Low Density Lipoprotein and Lipoprotein-Containing Circulating Immune Complexes as Diagnostic and Prognostic Biomarkers of Atherosclerosis and Type 1 Diabetes Macrovascular Disease

In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity of modified LDL results in induction of self-antibodies specific to a certain type of modified LDL. The antibodies react with modified LDL forming circulating immune complexes. Circulating immune complexes exhibit prominent immunomodulatory properties that influence atherosclerotic inflammation. Compared to freely circulating modified LDL; modified LDL associated with the immune complexes have a more robust atherogenic and proinflammatory potential. Various lipid components of the immune complexes may serve not only as diagnostic but also as essential predictive markers of cardiovascular events in atherosclerosis. Accumulating evidence indicates that LDL-containing immune complexes can also serve as biomarker for macrovascular disease in type 1 diabetes.     

Effect of Lowering Asymmetric Dimethylarginine (ADMA) on Vascular Pathology in Atherosclerotic ApoE-Deficient Mice with Reduced Renal Mass

The purpose of the work was to study the impact of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) and its degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH1), on atherosclerosis in subtotally nephrectomized (SNX) ApoE-deficient mice. Male DDAH1 transgenic mice (TG, n = 39) and C57Bl/6J wild-type littermates (WT, n = 27) with or without the deletion of the ApoE gene underwent SNX at the age of eight weeks. Animals were sacrificed at 12 months of age, and blood chemistry, as well as the extent of atherosclerosis within the entire aorta were analyzed. Sham treated (no renal mass reduction) ApoE-competent DDAH1 transgenic and wild-type littermates (n = 11) served as a control group. Overexpression of DDAH1 was associated with significantly lower ADMA levels in all treatment groups. Surprisingly, SNX mice did not exhibit higher ADMA levels compared to sham treated control mice. Furthermore, the degree of atherosclerosis in ApoE-deficient mice with SNX was similar in mice with or without overexpression of DDAH1. Overexpression of the ADMA degrading enzyme, DDAH1, did not ameliorate atherosclerosis in ApoE-deficient SNX mice. Furthermore, SNX in mice had no impact on ADMA levels, suggesting a minor role of this molecule in chronic kidney disease (CKD) in this mouse model.     

Label-Free Quantitative Proteomics Reveals Differences in Molecular Mechanism of Atherosclerosis Related and Non-Related to Chronic Kidney Disease

The major cause of mortality in patients with chronic kidney disease (CKD) is atherosclerosis related to traditional and non-traditional risk factors. However, the understanding of the molecular specificity that distinguishes the risk factors for classical cardiovascular disease (CVD) and CKD-related atherosclerosis (CKD-A) is far from complete. In this study we investigated the disease-related differences in the proteomes of patients with atherosclerosis related and non-related to CKD. Plasma collected from patients in various stages of CKD, CVD patients without symptoms of kidney dysfunction, and healthy volunteers (HVs), were analyzed by a coupled label-free and mass spectrometry approach. Dysregulated proteins were confirmed by an enzyme-linked immunosorbent assay (ELISA). All proteomic data were correlated with kidney disease development and were subjected to bioinformatics analysis. One hundred sixty-two differentially expressed proteins were identified. By directly comparing the plasma proteomes from HVs, CKD, and CVD patients in one study, we demonstrated that proteins involved in inflammation, blood coagulation, oxidative stress, vascular damage, and calcification process exhibited greater alterations in patients with atherosclerosis related with CKD. These data indicate that the above nontraditional risk factors are strongly specific for CKD-A and appear to be less essential for the development of “classical” CVD.     

Diet and antiatherogenic aspects — a review

There is evidence that dietary changes could be associated with a significant decrease in blood lipids with a beneficial influence on all the risk factors of coronary heart disease (CHD). Dietary recommendations made for Americans do not appear to be suitable for Asians because most Asians are consuming a diet similar to the phase I diet advised by the American Heart Association (AHA). Several studies have demonstrated that foods such as guava, fish, fenugreek, mushroom, star gooseberry, onion, garlic, Bengal gram, blackgram, horsegram, redgram, parwar, konjac food, bitter gourd, oatmeal, soyabean, almonds, walnuts, elucine (ragi) and tapioca root can cause a beneficial change of blood lipids and decrease atherosclerosis. Several of these foods can also lower blood sugar, hyperinsulinemia and platelet‐aggregation. Banana, guava, musk melon, sweet lemon, lemon, tomato and star gooseberry may also diminish blood pressure. It has been demonstrated that a diet rich in these foods, if administered for a prolonged period, may cause a significant decrease in CHD and total mortality.     

The effects of food essential oils on cardiovascular diseases: A review

Essential oils (EO) are complex secondary metabolites, which are produced by aromatic plants and identified by their powerful odors. Present studies on EO and their isolated ingredients have drawn the attention of researchers to screen these natural products and evaluate their effect on the cardiovascular system. Some EO, and their active ingredients, have been reported to improve the cardiovascular system significantly by affecting vaso-relaxation, and decreasing the heart rate and exert a hypotension activity. Several mechanisms have been proposed for the role of EO and their main active components in promoting the health of the cardiovascular system. The objective of this review is to highlight the current state of knowledge on the functional role of EO extracted from plants for reducing the risk of cardiovascular diseases and their mechanisms of action. Research on EO has the potential to identify new bioactive compounds and formulate new functional products for the treatment of cardiovascular diseases such as arterial hypertension, angina pectoris, heart failure, and myocardial infarction.     

高脂血症引起小鼠内脏的基因特异性变化

通过给小鼠喂食高脂饲料建立小鼠高脂血症模型,并测定内脏中一系列相关基因的表达,为解明高脂血症形成的分子机理提供一定的理论基础.11只6周龄雄性ICR小鼠,随机分成两组:一组为基础饲料组(BD),另一组为高脂饲料组(HFD).实验结果表明:对比BD,HFD血清Tc,LDL-C,VLDL和HDL-C水平有显著上升(p<0.01),而Tg水平明显下降(p<0.05).在肝脏中,Sod基因和Gpx1基因表达显著下降,而ID1和LDL-r表达显著上升(p<0.05).心脏中,HFD的LPL基因表达明显上升(p<0.05).结果表明,上述基因表达水平的变化可能与高脂血症在生理方面带来的不良作用有关.     

Diminazene Aceturate Stabilizes Atherosclerotic Plaque and Attenuates Hepatic Steatosis in apoE-Knockout Mice by Influencing Macrophages Polarization and Taurine Biosynthesis

Atherosclerosis and nonalcoholic fatty liver disease are leading causes of morbidity and mortality in the Western countries. The renin–angiotensin system (RAS) with its two main opposing effectors, i.e., angiotensin II (Ang II) and Ang-(1–7), is widely recognized as a major regulator of cardiovascular function and body metabolic processes. Angiotensin-converting enzyme 2 (ACE2) by breaking-down Ang II forms Ang-(1–7) and thus favors Ang-(1–7) actions. Therefore, the aim of our study was to comprehensively evaluate the influence of prolonged treatment with ACE2 activator, diminazene aceturate (DIZE) on the development of atherosclerotic lesions and hepatic steatosis in apoE^−/− mice fed a high-fat diet (HFD). We have shown that DIZE stabilized atherosclerotic lesions and attenuated hepatic steatosis in apoE^−/− mice fed an HFD. Such effects were associated with decreased total macrophages content and increased α-smooth muscle actin levels in atherosclerotic plaques. Moreover, DIZE changed polarization of macrophages towards increased amount of anti-inflammatory M2 macrophages in the atherosclerotic lesions. Interestingly, the anti-steatotic action of DIZE in the liver was related to the elevated levels of HDL in the plasma, decreased levels of triglycerides, and increased biosynthesis and concentration of taurine in the liver of apoE^−/− mice. However, exact molecular mechanisms of both anti-atherosclerotic and anti-steatotic actions of DIZE require further investigations.