A perspective for atherosclerosis vaccination: Is there a place for plant-based vaccines?

Alternatives to pharmacological treatments for atherosclerosis are highly desirable in terms of cost and compliance. During the last two decades several vaccination strategies have been reported as an effort to develop immunotherapeutic treatments. This approach consists on eliciting immune responses able to modulate either the atherosclerosis-associated inflammatory processes or the activity of some physiological mechanisms that are up-regulated under this pathologic condition. In particular, the apolipoprotein B100 (ApoB100) and the cholesterilester transferase protein (CETP) have been targeted in these strategies. It is considered that recent progress in the development of experimental models of oral vaccines against atherosclerosis has opened a new avenue in the field: as plant-based vaccines are considered a viable platform for vaccine production and delivery at low costs, they could serve as an oral-delivered therapeutic approach for atherosclerosis in an economical and patient-friendly manner. The rationale of the design, development and evaluation of possible plant-based vaccines against atherosclerosis is discussed in this review. We identify within this approach a significant trend that will positively impact the field of atherosclerosis vaccination.     

Measurement of Atherosclerosis: Development of an Atherosclerosis Severity Index

Treatment of hypertension has succeeded in preventing the complications attributable to pressure, including heart failure and the arteriolar complications such as brain hemorrhage and renal failure. Recent understanding that antihypertensive drugs have effects on lipoproteins and flow disturbances that may be important in atherosclerosis progression, and the recent development of drugs that are more effective in treating hyperlipidemia, have given impetus to the design of studies to test whether interventions are anti-atherosclerotic. Since studies depending on clinical endpoints by necessity consume vast resources, it is desirable to develop methods for measurement of atherosclerosis, in order to make it possible to conduct intervention studies efficiently. Because angiographic methods are costly and associated with risk, and many patients are unable or unwilling to undergo followup angiography at the end of a study, we are developing an atherosclerosis severity index based on clinical and noninvasive ultrasound assessment. This scale can be used as a surrogate outcome in place of, or complementary to angiographic measurement of atherosclerosis, to avoid costly loss of subjects in intervention studies. It has the additional advantage that it is suitable for repeated assessment over time, permitting the power of analyses such as life table analysis which look at time to development of endpoints.     

Current Strategies for Atherosclerosis and Lowering Cholesterol

Atherosclerosis is a multifactorial disorder in which nutritional factors are closely related to a number of the manifestations of the disease. Sounder nutritional principles might therefore prevent atherosclerosis itself or its major complications. Optimising nutrients would diminish monocyte adhesion to endothelium, suppress platelet aggregation, prevent oxidative modification of lipoproteins, minimise activation of coagulant factors and reduce the flux of cholesterol and of atherogenic lipoproteins through plasma.

Optimising the mix of dietary fatty acids should have the highest priority. Emphasis should be placed on those fatty acids, such as those derived from fish, which modify several cardiovascular risk factors, including plasma lipids, blood pressure and coagulation factors. Reduction of risk factors is also achieved but to a lesser extent by reducing total fat intake, reducing dietary cholesterol, optimising the mix of starches and fibre and increasing plant foods generally.

A developing strategy is to identify genetic predisposition to environmentally induced hyperlipidaemia, since most forms of hyperlipidaemia reflect interactions between genetic and dietary factors.     

C‐reactive protein and tumor necrosis factor‐alpha in relation to insulin‐mediated glucose uptake,smoking and atherosclerosis

Objectives. To examine the hypothesis that serum concentration of C‐reactive protein (CRP) is inversely associated with insulin sensitivity and obesity, and that this may by mediated by tumor necrosis factor‐α (TNFα) and interleukin‐6 (IL‐6). Material and methods. Cross‐sectional, one‐center study of a population‐based sample of 58‐year‐old Swedish men (n = 98). Exclusion criteria were cardiovascular disease, clinical diabetes mellitus and/or continuous cardiovascular medication. Glucose infusion‐rate (euglycemic hyperinsulinemic clamp), adjusted for fat‐free mass, which together with total body fat was measured by dual‐energy X‐ray absorptiometry. Serum concentrations of CRP, TNFα, soluble TNFα receptor 2 (sTNFAR2), IL‐6 determined by ELISA. Ultrasound was used to measure intima‐media thickness (IMT) in both common carotid arteries, carotid bulbs and in the right femoral artery. Results. CRP was inversely associated with insulin sensitivity (r = ?0.28, p<0.01) and with total body fat (r = 0.31, p<0.01), but not independently of the TNFα and sTNFAR2 product. Serum CRP, TNFα, sTNFAR2, but not IL‐6, were associated with low insulin sensitivity, total body fat, abdominal obesity, hyperinsulinemia, hypertriglyceridemia, low HDL cholesterol and small LDL particles, i.e. the metabolic syndrome. These associations were independent of smoking and carotid and femoral artery IMT. Conclusions. Serum concentrations of CRP were related to insulin sensitivity and accompanying factors constituting the metabolic syndrome. The results indicate that this association may be mediated by adipose tissue and TNFα effects, the latter measured as the product of TNFα and sTNFAR2. This was a cross‐sectional study and causality cannot be proven.     

Albuminuria within the normal range and ultrasound‐assessed atherosclerosis in the AIR study: a 9‐year follow‐up of 58‐year‐old clinically healthy men

Background:Microalbuminuria, traditionally defined as 30–300 mg urinary albumin/24 h, predicts renal impairment and cardiovascular disease. Studies suggest that also a far lower urinary albumin excretion (UAE) can predict clinical outcome. Intima media thickness (IMT) is an established estimate of atherosclerosis. In this study, we investigated the predictive value of UAE within the normal rate (UAE–n) for the progression of IMT in the carotid and femoral arteries. Methods: We included 325 clinically healthy men with normoalbuminuria. Anthropometrics, urine and blood samples were taken and IMT in the carotid and femoral arteries were assessed by B–mode ultrasound at baseline and after 3 and 9 years. The annual progression rate of IMT (r–IMT) was calculated. Results: UAE–n correlated with carotid IMT at baseline and after 3 and 9 years, but not with r–IMT. In a regression analysis, only HDL and baseline IMT remained as statistically significant co–variates to mean IMT at 9 years. IMT in the femoral artery and r–IMT at any time–point did not correlate to baseline UAE. Conclusion: UAE–n was associated with carotid IMT after 3 and 9 years but not r–IMT or with femoral artery IMT. Carotid IMT after 9 years' follow–up was independently related to baseline IMT and HDL cholesterol. In this cohort of 58–year–old men, our interpretation is that UAE–n is not associated with the increase in carotid and femoral artery IMT observed after 9 years.     

Elimination of endoplasmic reticulum stress and cardiovascular,type 2 diabetic,and other metabolic diseases

Abstract

Multiple factors including unhealthy living habits influence the life-maintaining functions of the endoplasmic reticulum (ER) and induce ER stress and metabolic abnormalities. The ER responds to the disturbances by activating mechanisms that increase the capacity to eliminate ER stress. This article elucidates the effects of ER activation that eliminates both ER stress and associated cardiovascular, type 2 diabetic (DM2), and other metabolic diseases. ER-activating compounds eliminate ER stress by lowering elevated cholesterol, regress atherosclerosis, decrease cardiovascular mortality, reduce blood glucose and insulin, and, together with the normalization of glucose–insulin homeostasis, remove insulin resistance, pancreatic β-cell failure, and DM2. A deficient cytochrome P450 activity in hepatic ER leads to cholesterol accumulation that induces stress and xanthoma formation, whereas P450-activating therapy up-regulates apolipoprotein AI and LDLR genes, down-regulates apolipoprotein B gene, and produces an antiatherogenic plasma lipoprotein profile. The ER activation reduces the stress also by eliminating hepatic fat and converting saturated fatty acids (FAs) to unsaturated FAs. Cognitive processes require gene expression modification, and preclinical studies indicate that ER-activating therapy improves cognition. Promotion of healthy lifestyle choices and indicated therapies are key factors in the prevention and elimination of ER stress and associated global health problems.     

Outcomes of Carotid Revascularization in Patients with Contralateral Carotid Artery Occlusion

1. Download : Download high-res image (331KB)
2. Download : Download full-size image

     

Study on the correlation between the concentration of plasma lipoprotein-associated phospholipase A2 and coronary heart disease

ObjectiveThis study explores the correlation between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) and coronary heart disease (CHD) by comparing the level of plasma Lp-PLA2 in the plasma of patients with different types of CHD.MethodsBlood samples were collected from 56 patients diagnosed with CHD by the Department of Cardiology of the First People''s Hospital of Foshan and 34 healthy subjects from February 2013 to January 2014. We measured the concentration of plasma Lp-PLA2 and determined the levels of total cholesterol (Tch), triglyceride (TG), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), high density lipoprotein-cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c), lipoprotein a (Lp(a)), glucose (Glu), and high-sensitivity C-reactive protein (hs-CRP). The concentration of plasma Lp-PLA2 in the healthy control group and each subgroup of CHD patients were compared and analyzed for correlations of plasma Lp-PLA2 between the patients in different CHD subgroups and several laboratory indicators.ResultsThe concentration of plasma Lp-PLA2 in each subgroup of CHD was significantly higher than in the control group (P < 0.05). The concentration of Lp-PLA2 in the unstable angina pectoris (UAP) group and acute myocardial infarction (AMI) group were significantly higher than in the stable angina pectoris (SAP) group (P < 0.05), and the concentration of plasma Lp-PLA2 in the AMI group was significantly higher than in the UAP group (P < 0.05). The concentration of plasma Lp-PLA2 in the CHD group merely showed a positive correlation (r = 0.493, P < 0.05) with the hs-CRP group, but the levels of Tch, TG, Apo-A1, Apo-B, HDL-c, LDL-c, Lp(a) and Glu did not.ConclusionsThe concentration of plasma Lp-PLA2 in patients with CHD was higher than that in the control group. The concentration of plasma Lp-PLA2 in the subgroups of CHD patients varied greatly from each other. The inflammatory response of atherosclerosis might be resulted from the synergy of plasma Lp-PLA2 and hs-CRP.     

Pentraxins,Anti-pentraxin Antibodies,and Atherosclerosis

Atherosclerosis is a disease of the vascular wall, which predominantly affects large and medium-sized arteries. It represents a leading cause of morbidity and mortality in the Western world. In the last few decades, it has been clearly shown that immune system plays a relevant role in atherogenesis. The effectors of both innate and adaptive immunity, including immune cells, cell or soluble receptors, cytokines, chemokines, complement components or coagulation systems, and autoantibodies are able to modulate atherosclerosis. Among proteins belonging to innate immunity, the highly conserved pentraxin family, which encompass C-reactive protein (CRP), serum amyloid P (SAP), and the long pentraxin 3 (PTX3) seems to be directly involved in the induction and progression of atherosclerosis. By immunohistochemical staining, pentraxins were found within the atherosclerotic plaques where they could play a key role interacting with atherogenic-modified lipoproteins, favoring the formation of foam cells, and exerting a proinflammatory action. Pentraxin serum levels have been shown to be associated with clinical and subclinical atherosclerosis in general population. Antibodies against pentraxins have been demonstrated in patients with autoimmune diseases, but their role in atherogenesis is still controversial.