Lycopene and preclinical carotid atherosclerosis

Evidence from epidemiological and clinical studies suggests a possible correlation between serum antioxidant levels and cardiovascular disease risk. High plasma concentrations of lycopene have been associated with reduced prevalence of cardiovascular disease. The aim of this study is to compare plasma concentrations of lycopene in subjects with or without ultrasonic evidence of asymptomatic carotid atherosclerosis. One hundred and twenty subjects underwent physical examination, ultrasonic measurement of common carotid artery intima-media thickness and serum profile analysis. Logistic regression methods and analysis of variance were used to determine whether differences existed between participants with or without evidence of carotid atherosclerosis. Of the 120 participants, 58 exhibited evidence of carotid atherosclerosis. Participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly higher serum concentrations of total cholesterol, LDL-cholesterol and triglycerides. In contrast, participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly lower plasma concentrations of lycopene. These data suggest that higher serum levels of lycopene may play a protective role versus cardiovascular diseases, in particular carotid atherosclerosis.     

血浆游离DNA检测在心血管系统疾病诊断中的应用

心血管疾病发病率和病死率居高不下,寻求敏感性高的生物学指标帮助早期诊断和改善预后意义重大.血浆游离DNA(cell-free DNA,cfDNA)是一类存在于血浆、尿液及其他体液中游离于细胞之外的双链DNA片段.血浆cfDNA水平在心血管疾病的早期明显升高,提示其可能是心血管疾病的潜在生物标志物.为了更深入理解cfDN...     

Proprotein convertase subtilisin/kexin type 9: A new target molecule for gene therapy

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel target for controlling plasma levels of low-density lipoprotein cholesterol (LDL-C) and decreasing the risk of cardiovascular diseases. At present it is clear that the major classes of commonly prescribed lipid-lowering medications increase serum PCSK9 levels and fail to protect a significant percentage of patients from cardiovascular events. Therefore development of new LDL-C lowering medications that either do not increase circulating PCSK9 levels or work through inhibition of PCSK9 expression and protease activity is a highly desirable approach to overcome hypercholesterolemia. Since there are several agents which are being evaluated in human preclinical and clinical trials, this review summarizes current therapeutic strategies targeting PCSK9, including specific antibodies, antisense oligonucleotides, small interfering RNAs (siRNAs) and other small-molecule inhibitors.     

Serum C‐reactive protein in the prediction of cardiovascular diseases: Overview of the latest clinical studies and public health practice

Cardiovascular disease is the most common cause of morbidity and mortality globally. Epidemiological studies using high‐sensitivity assays for serum C‐reactive protein have shown a consistent association between cardiovascular disease risk and serum C‐reactive protein concentrations. C‐reactive protein is a biomarker for inflammation, and has been established in clinical practice as an independent risk factor for cardiovascular disease events. There is evidence that serum C‐reactive protein is an excellent biomarker of cardiovascular disease and is also an independent and strong predictor of adverse cardiovascular events. Further characterization of the impact and influence of lifestyle exposures and genetic variation on the C‐reactive protein response to cardiovascular disease events may have implications for the therapeutic approaches to reduce cardiovascular disease events. This review summarizes the studies that have examined the association between serum C‐reactive protein and the risk of cardiovascular disease. We also discuss the impact of independent factors and C‐reactive protein genetic polymorphisms on baseline plasma C‐reactive protein levels.     

Plasma p-Cresol Lowering Effect of Sevelamer in Peritoneal Dialysis Patients: Evidence from a Cross-Sectional Observational Study

p-Cresol is a by-product of the metabolism of aromatic aminoacid operated by resident intestinal bacteria. In patients with chronic kidney disease, the accumulation of p-cresol and of its metabolite p-cresyl-sulphate causes endothelial dysfunction and ultimately increases the cardiovascular risk of these patients. Therapeutic strategies to reduce plasma p-cresol levels are highly demanded but not available yet. Because it has been reported that the phosphate binder sevelamer sequesters p-cresol in vitro we hypothesized that it could do so also in peritoneal dialysis patients. To explore this hypothesis we measured total cresol plasma concentrations in 57 patients with end-stage renal disease on peritoneal dialysis, 29 receiving sevelamer for the treatment of hyperphosphatemia and 28 patients not assuming this drug. Among the patients not assuming sevelamer, 16 were treated with lanthanum whereas the remaining 12 received no drug because they were not hyperphosphatemic. Patients receiving sevelamer had plasma p-cresol and serum high sensitivity C-reactive protein concentrations significantly lower than those receiving lanthanum or no drug. Conversely, no difference was observed among the different groups either in residual glomerular filtration rate, total weekly dialysis dose, total clearance, urine volume, protein catabolic rate, serum albumin or serum phosphate levels. Multiple linear regression analysis showed that none of these variables predicted plasma p-cresol concentrations that, instead, negatively correlated with the use of sevelamer. These results suggest that sevelamer could be an effective strategy to lower p-cresol circulating levels in peritoneal dialysis patients in which it could also favorably affect cardiovascular risk because of its anti-inflammatory effect.     

Comparative protein profiling of serum and plasma using an antibody suspension bead array approach

In the pursuit towards a systematic analysis of human diseases, array‐based approaches within antibody proteomics offer high‐throughput strategies to discover protein biomarkers in serum and plasma. To investigate the influence of sample preparation on such discovery attempts, we report on a systematic effort to compare serum and plasma protein profiles determined with an antibody suspension bead array. The intensity levels were used to define protein profiles and no significant differences between serum and plasma were observed for 79% of the 174 antibodies (targeting 156 proteins). By excluding 36 antibodies giving rise to differential intensity levels, cluster analysis revealed donor‐specific rather than preparation‐dependent grouping. With a cohort from a clinically relevant medical condition, the metabolic syndrome, the influence of the sample type on a multiplexed biomarker discovery approach was further investigated. Independent comparisons of protein profiles in serum and plasma revealed an antibody targeting ADAMTSL‐4, a protein that would qualify to be studied further in association with the condition. In general, the preparation type had an impact on the results of the applied antibody suspension bead array, and while the technical variability was equal, plasma offered a greater biological variability and allowed to give rise to more discoveries than serum.     

Adrenomedullin as a sensitive marker for coronary and peripheral arterial complications in patients with atherosclerotic risks

Plasma adrenomedullin (AM) levels are elevated in various pathological states including cardiovascular and inflammatory diseases. The present study investigated whether an increased AM level is a marker of vascular complications in patients with atherosclerotic risks. In 114 patients with cardiovascular risks and/or diseases including ischemic heart disease (IHD) and peripheral arterial disease (PAD), plasma AM concentration and other inflammatory markers such as high sensitive C-reactive protein (CRP) and interleukin (IL)-6 were examined. The plasma AM level was not altered by the absence or presence of each of four major risk factors, i.e., hypertension, diabetes mellitus, hyperlipidemia, and smoking and its level was not significantly correlated with blood pressure, plasma glucose, or serum lipid levels. The patients with IHD had a significantly higher concentration of plasma AM than those without IHD. The AM level in subjects with PAD was also increased significantly compared with those without PAD. The plasma AM was strongly correlated with inflammatory parameters such as CRP and IL-6. Among AM, CRP, and IL-6, however, only AM was an independent predictor for both IHD and PAD by multiple logistic regression analysis. Our findings suggest the possibility that plasma AM is a novel sensitive marker for the presence of vascular lesions in patients with atherosclerotic risks.     

Role of proteomic technologies in understanding risk of arterial thrombosis

Arterial thrombosis is a pivotal event in the development of cardiovascular diseases. Plasma and cellular proteins have the potential to influence thrombus morphology and function. This review summarizes the latest studies to use proteomic technologies to characterize the cellular and plasma components involved in arterial thrombosis, with a view to understanding the pathogenesis and treatment of acute cardiovascular diseases. Proteomic approaches have been extensively used to profile the proteome of endothelial cells, leukocytes, vascular smooth muscle cells, platelets and plasma in the search for risk factors for cardiovascular disease; however, further work is required to validate the direct contribution of these proteins to arterial thrombosis.     

Serum triglycerides and risk of cardiovascular disease

Dyslipidemia, especially elevated serum levels of cholesterol, is causally related to cardiovascular disease. The specific role of triglycerides has long been controversial. In this article we discuss the role of serum triglycerides in relation to the risk of cardiovascular disease. First, the (patho)physiology of triglycerides is described, including the definition and a short summary of the primary and secondary causes of hypertriglyceridemia. Furthermore, we will give an overview of the published epidemiological studies concerning hypertriglyceridemia and cardiovascular disease to support the view that triglyceride-rich lipoproteins are an independently associated risk factor. Finally, treatment strategies and treatment targets are discussed. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.     

Metabolic syndrome in rheumatic diseases: epidemiology,pathophysiology, and clinical implications

Subjects with metabolic syndrome–a constellation of cardiovascular risk factors of which central obesity and insulin resistance are the most characteristic–are at increased risk for developing diabetes mellitus and cardiovascular disease. In these subjects, abdominal adipose tissue is a source of inflammatory cytokines such as tumor necrosis factor-alpha, known to promote insulin resistance. The presence of inflammatory cytokines together with the well-documented increased risk for cardiovascular diseases in patients with inflammatory arthritides and systemic lupus erythematosus has prompted studies to examine the prevalence of the metabolic syndrome in an effort to identify subjects at risk in addition to that conferred by traditional cardiovascular risk factors. These studies have documented a high prevalence of metabolic syndrome which correlates with disease activity and markers of atherosclerosis. The correlation of inflammatory disease activity with metabolic syndrome provides additional evidence for a link between inflammation and metabolic disturbances/vascular morbidity.     

脂蛋白电子显微结构研究的优化负染方法

人类心血管等疾病与胆固醇含量的高低有着十分密切的关系．人体内胆固醇主要通过血液中的脂蛋白来调节和运载．因此,新一代调节胆固醇的药物设计迫切地需要揭示脂蛋白分子结构与功能之间的关系．由于脂蛋白分子的成分高度复杂、结构特征灵活、尺寸微小,传统的蛋白质结构标定技术,如X射线衍射、核磁共振谱、质谱和冷冻电子显微镜等手段都面临着巨大的困难．针对这一问题,任罡小组最近提出一种优化的电镜负染制备方法,可以观测到单个脂蛋白分子的空间结构．此方法应用的成功,使得对单个脂蛋白分子的结构研究成为可能．同时也证明该负染色技术作为一种普遍的实验手段,可以用于对蛋白质小分子的结构研究,从而将促进新一代蛋白质分子药物的研发．     

Anthocyanin-Rich Juice Lowers Serum Cholesterol,Leptin, and Resistin and Improves Plasma Fatty Acid Composition in Fischer Rats

Obesity and obesity-associated diseases e.g. cardiovascular diseases and type 2 diabetes are spread worldwide. Anthocyanins are supposed to have health-promoting properties, although convincing evidence is lacking. The aim of the present study was to investigate the effect of anthocyanins on several risk factors for obesity-associated diseases. Therefore, Fischer rats were fed anthocyanin-rich grape-bilberry juice or an anthocyanin-depleted control juice for 10 weeks. Intervention with anthocyanin-rich grape-bilberry juice reduced serum cholesterol and tended to decrease serum triglycerides. No effects were seen for serum non-esterified fatty acids, glucose, and insulin. Anthocyanin-rich grape-bilberry juice intervention reduced serum leptin and resistin, but showed no influence on serum adiponectin and secretion of adipokines from mesenteric adipose tissue. Furthermore, anthocyanin-rich grape-bilberry juice increased the proportion of polyunsaturated fatty acids and decreased the amount of saturated fatty acids in plasma. These results indicate that anthocyanins possess a preventive potential for obesity-associated diseases.     

胆汁酸受体FXR 的研究进展

法尼酯衍生物X受体(FXR)是一种胆汁酸受体,在胆汁酸代谢和胆固醇代谢中发挥重要作用,并有望成为降低胆固醇,治疗某些心血管病及肝脏疾病的治疗靶点。本文介绍了FXR的发现、FXR在调控胆汁酸和脂质代谢中的作用,以及FXR在心血管疾病治疗中的应用前景。     

Potential application of biomimetic exosomes in cardiovascular disease: focused on ischemic heart disease

Cardiovascular disease, especially ischemic heart disease, is a major cause of mortality worldwide. Cardiac repair is one of the most promising strategies to address advanced cardiovascular diseases. Despite moderate improvement in heart function via stem cell therapy, there is no evidence of significant improvement in mortality and morbidity beyond standard therapy. The most salutary effect of stem cell therapy are attributed to the paracrine effects and the stem cell-derived exosomes are known as a major contributor. Hence, exosomes are emerging as a promising therapeutic agent and potent biomarkers of cardiovascular disease. Furthermore, they play a role as cellular cargo and facilitate intercellular communication. However, the clinical use of exosomes is hindered by the absence of a standard operating procedures for exosome isolation and characterization, problems related to yield, and heterogeneity. In addition, the successful clinical application of exosomes requires strategies to optimize cargo, improve targeted delivery, and reduce the elimination of exosomes. In this review, we discuss the basic concept of exosomes and stem cell-derived exosomes in cardiovascular disease, and introduce current efforts to overcome the limitations and maximize the benefit of exosomes including engineered biomimetic exosomes.     

Cell-derived microparticles in atherosclerosis: biomarkers and targets for pharmacological modulation?

Cardiovascular diseases remain an important cause of morbi-mortality. Atherosclerosis, which predisposes to cardiovascular disorders such as myocardial infarction and stroke, develops silently over several decades. Identification of circulating biomarkers to evaluate cardiovascular event risk and pathology prognosis is of particular importance. Microparticles (MPs) are small vesicles released from cells upon apoptosis or activation. Microparticles are present in blood of healthy individuals. Studies showing a modification of their concentrations in patients with cardiovascular risk factors and after cardiovascular events identify MPs as potential biomarkers of disease. Moreover, the pathophysiological properties of MPs may contribute to atherosclerosis development. In addition, pharmacological compounds, used in the treatment of cardiovascular disease, can reduce plasma MP concentrations. Nevertheless, numerous issues remain to be solved before MP measurement can be applied as routine biological tests to improve cardiovascular risk prediction. In particular, prospective studies to identify the predictive values of MPs in pathologies such as cardiovascular diseases are needed to demonstrate whether MPs are useful biomarkers for the early detection of the disease and its progression.     

Plasma Clusterin and Lipid Profile: A Link with Aging and Cardiovascular Diseases in a Population with a Consistent Number of Centenarians

The role of Clusterin in attenuation of inflammation and reverse cholesterol transfer makes this molecule a potential candidate as a marker for cancer, cardiovascular disease, diabetes mellitus, and metabolic syndrome. In elderly subjects cardiovascular diseases represent the primary cause of death and different clinical studies have shown a positive correlation of these diseases with changes in the lipid pattern. This work aimed at evaluating the relationship between circulating clusterin and the biochemical parameters that characterize the lipid profile of a Sardinian population divided into five age groups including centenarians; the high frequency in Sardinia of these long-lived individuals gave us the opportunity to extend the range of the age groups to be analyzed to older ages and to better evaluate the changes in the lipid balance during ageing and its relationship with clusterin concentration in plasma. Our results showed that Clusterin concentration values of the youngest group were more similar with the centenarian’s group compared to the other age groups, and a positive correlation arises with LDL. Furthermore given the high prevalence of cardiovascular diseases in the population examined and the association of Clusterin with these pathologies we evaluated Clusterin concentration variation in two groups with or without cardiovascular diseases. In presence of cardiovascular disease, Clusterin is significantly related to the most atherogenic components of lipid profile (total cholesterol and LDL), especially in women, suggesting its potential role in modulating cardiovascular metabolic risk factors.     

天然产物在新药开发中的应用--HMG-CoA还原酶抑制剂新药的发现对天然产物研究与开发的启示

自1973年发现第一个作用于HMG-CoA还原酶的化合物mevastatin以来,多个具有HMG-CoA还原酶抑制活性的抗高血脂新药被开发成功,并成为治疗高血脂症的首选药物。在此简单介绍该类新药的发现与开发过程,并就天然产物的研究与开发提出一点个人见解。     

Gout. Hyperuricemia and cardiovascular disease: how strong is the evidence for a causal link?

An association between high levels of serum urate and cardiovascular disease has been proposed for many decades. However, it was only recently that compelling basic science data, small clinical trials, and epidemiological studies have provided support to the idea of a true causal effect. In this review we present recently published data that study the association between hyperuricemia and selected cardiovascular diseases, with a final conclusion about the possibility of this association being causal.