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The decision to use the optimal animal model to mimic the various types of cardiovascular disease is a critical one for a basic scientist. Clinical cardiovascular disease can be complex and presents itself as atherosclerosis, hypertension, ischemia/reperfusion injury, myocardial infarcts, and cardiomyopathies, amongst others. This may be further complicated by the simultaneous presence of two or more cardiovascular lesions (for example, atherosclerosis and hypertension) and co-morbidities (i.e., diabetes, infectious disease, obesity, etc). This variety and merging of disease states creates an unusually difficult situation for the researcher who needs to identify the optimal animal model that is available to best represent all of the characteristics of the clinical cardiovascular disease. The present manuscript reviews the characteristics of the various animal models of cardiovascular disease available today, their advantages and disadvantages, with the goal to allow the reader access to the most recent data available for optimal choices prior to the initiation of the study. The animal species that can be chosen, the methods of generating these models of cardiovascular disease, as well as the specific cardiovascular lesions involved in each of these models are reviewed. A particular focus on the JCR:LA- cp rat as a model of cardiovascular disease is discussed., Competing Interests: There are no competing interests that are financial or non-financial or any other relationship that might bias or be seen to bias our work.

Fatty acids come in a variety of structures and, because of this, create a variety of functions for these lipids. Some fatty acids have a role to play in energy metabolism, some help in lipid storage, cell structure, the physical state of the lipid, and even in food stability. Fatty acid metabolism plays a particularly important role in meeting the energy demands of the heart. It is the primary source of myocardial energy in control conditions. Its role changes dramatically in disease states in the heart, but the pathologic role these fatty acids play depends upon the type of cardiovascular disease and the type of fatty acid. However, no matter how good a food is for one's health, its taste will ultimately become a deciding factor in its influence on human health. No food will provide health benefits if it is not ingested. This review discusses the taste characteristics of culinary oils that contain fatty acids and how these fatty acids affect the performance of the heart during healthy and diseased conditions. The contrasting contributions that different fatty acid molecules have in either promoting cardiac pathologies or protecting the heart from cardiovascular disease is also highlighted in this article.

Food quality and nutritional habits strongly influence human health status. Extensive research has been conducted to confirm that foods rich in biologically active nutrients have a positive impact on the onset and development of different pathological processes, including cardiovascular diseases. However, the underlying mechanisms by which dietary compounds regulate cardiovascular function have not yet been fully clarified. A growing number of studies confirm that bioactive food components modulate various signaling pathways which are involved in heart physiology and pathology. Recent evidence indicates that microRNAs (miRNAs), small single-stranded RNA chains with a powerful ability to influence protein expression in the whole organism, have a significant role in the regulation of cardiovascular-related pathways. This review summarizes recent studies dealing with the impact of some biologically active nutrients like polyunsaturated fatty acids (PUFAs), vitamins E and D, dietary fiber, or selenium on the expression of many miRNAs, which are connected with cardiovascular diseases. Current research indicates that the expression levels of many cardiovascular-related miRNAs like miRNA-21, -30 family, -34, -155, or -199 can be altered by foods and dietary supplements in various animal and human disease models. Understanding the dietary modulation of miRNAs represents, therefore, an important field for further research. The acquired knowledge may be used in personalized nutritional prevention of cardiovascular disease or the treatment of cardiovascular disorders.

Food constituents can either promote cardiovascular health or serve in its demise. In view of the lack of more effective pharmacological interventions in cardiovascular disease (CVDs), attention has focused on the potential protective effects of diet. Food components and their metabolites are emerging as major regulators of the human epigenome, which is being linked to CVDs. In this review, we summarize data from studies that suggest an important role for bioactive food compounds in cardioprotection and the potential for harnessing the epigenome as a nutrient sensor target in CVDs. While clinical data strongly support a role for effective diet intervention in CVDs protection, studies linking changes to human epigenome are now warranted for mechanistic insight and development of personalized care., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Flaxseed (Linum usitatissimum) is composed of a unique combination of bioactive components that appear to generate, through either an isolated or a synergistic action, a significant beneficial effect on the cardiovascular system. With a significant increase in the generation of data on the dietary impact of flaxseed on the cardiovascular system, a review of where we stand - what we know and what we still need to understand about these effects on the heart and the vasculature - was thought to be of value and the rationale for this paper. For example, although we now know how to deliver the bioactives most efficiently (oil versus ground seed versus whole seed), we do not know how different foods can influence that delivery. Further, we know flaxseed has anti-arrhythmic, anti-atherogenic, anti-hypertensive, and cholesterol-lowering actions in animal studies and some selected human trials but much more needs to be learned, particularly in human trials. These results have justified further commitment of resources to the initiation of human trials. Because of the impact of nutrition on many chronic diseases, this may not only be true for the effects of flaxseed on cardiovascular disease but may be just as relevant for many other disease conditions.

Cardiovascular disease remains the leading cause of mortality and morbidity worldwide. The inclusion of functional foods and natural health products in the diet are gaining increasing recognition as integral components of lifestyle changes in the fight against cardiovascular disease. Several preclinical and clinical studies have shown the beneficial cardiovascular effects of dietary supplementation with flaxseed. The cardiovascular effects of dietary flaxseed have included an antihypertensive action, antiatherogenic effects, a lowering of cholesterol, an anti-inflammatory action, and an inhibition of arrhythmias. Its enrichment in the ω-3 fatty acid α-linolenic acid and the antioxidant lignan secoisolariciresinol diglucoside as well as its high fiber content have been implicated primarily in these beneficial cardiovascular actions. Although not as well recognized, flaxseed is also composed of other potential bioactive compounds such as proteins, cyclolinopeptides, and cyanogenic glycosides, which may also produce biological actions. These compounds could also be responsible for the cardiovascular effects of flaxseed. This article will not only summarize the cardiovascular effects of dietary supplementation with flaxseed but also review its bioactive compounds in terms of their properties, biological effects, and proposed mechanisms of action. It will also discuss promising research directions for the future to identify additional health-related benefits of dietary flaxseed.

Oxylipins are a group of fatty acid metabolites generated via oxygenation of polyunsaturated fatty acids and are involved in processes such as inflammation, immunity, pain, vascular tone, and coagulation. As a result, oxylipins have been implicated in many conditions characterized by these processes, including cardiovascular disease and aging. The best characterized oxylipins in relation to cardiovascular disease are derived from the ω-6 fatty acid arachidonic acid. These oxylipins generally increase inflammation, hypertension, and platelet aggregation, although not universally. Similarly, oxylipins derived from the ω-6 fatty acid linoleic acid generally have more adverse than beneficial cardiovascular effects. Alternatively, most oxylipins derived from 20- and 22-carbon ω-3 fatty acids have anti-inflammatory, antiaggregatory, and vasodilatory effects that help explain the cardioprotective effects of these fatty acids. Much less is known regarding the oxylipins derived from the 18-carbon ω-3 fatty acid α-linolenic acid, but clinical trials with flaxseed supplementation have indicated that these oxylipins can have positive effects on blood pressure. Normal aging also is associated with changes in oxylipin levels in the brain, vasculature, and other tissues, indicating that oxylipin changes with aging may be involved in age-related changes in these tissues. A small number of trials in humans and animals with interventions that contain either 18-carbon or 20- and 22-carbon ω-3 fatty acids have indicated that dietary-induced changes in oxylipins may be beneficial in slowing the changes associated with normal aging. In summary, oxylipins are an important group of molecules amenable to dietary manipulation to target cardiovascular disease and age-related degeneration. NEW & NOTEWORTHY Oxylipins are an important group of fatty acid metabolites amenable to dietary manipulation. Because of the role they play in cardiovascular disease and in age-related degeneration, oxylipins are gaining recognition as viable targets for specific dietary interventions focused on manipulating oxylipin composition to control these biological processes., (Copyright © 2017 the American Physiological Society.)

Coronary heart disease is becoming a worldwide epidemic and diet and lifestyle are well known contributing factors. Identifying the kinds of foods that may have a cardioprotective or cardiotoxic effect and understanding their molecular mechanisms of action has become of increasing importance. Through largely epidemiological evidence, trans fatty acid (TFA) intake has been associated with a variety of cardiovascular complications including atherosclerosis. Traditionally, industrial TFAs (iTFAs) have been associated with these deleterious cardiovascular effects. However, there is a current body of research that suggests that ruminant trans fats (rTFAs) may have a cardioprotective role within the heart. The molecular mechanisms whereby TFAs are delivering their effects are largely unknown. In the following review, we discuss recent in vitro, animal and epidemiological research to better understand the effect of TFAs in the diet on cardiovascular disease, particularly atherosclerosis., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Flaxseed is an important source of alpha-linolenic acid an essential omega-3 fatty acid. The possibility that a supplementation of the diet with foods rich in alpha-linolenic acid, antioxidants and fiber (like flaxseed) has not been investigated., Methods/design: The primary objective is to determine whether consumption of a diet rich in FLAXseed over a one year period has any beneficial cardiovascular effects in patients with Peripheral Arterial Disease (FLAX-PAD study). This is a single center, prospective, double blinded, randomized controlled clinical trial aimed at in 110 patients over 40 years old and with peripheral arterial disease. Patients will receive 30 g of milled flaxseed (or placebo) per day. Primary endpoints are incidence of myocardial infarction and stroke. Secondary measures include: requirement for surgical interventions, exercise and cardiopulmonary performance, cardiac arrhythmias, serum lipid profile, arterial sufficiency, blood pressure, inflammatory profile, platelet function, changes in drug dosage levels, as well as nutrigenomic and biomarker profiles in the blood. Recruitment and baseline examinations started in October 2008. Baseline data of the 110 patients is shown., Conclusions: FLAX-PAD will generate data on the safety, tolerability, cardiovascular efficacy and genomic response to a diet rich in flaxseed. It will determine the effects on primary and secondary events (stroke, myocardial infarctions, angina pectoris, cardiac arrhythmias) as well as in secondary endpoints (exercise performance, blood pressure and circulating lipid levels) in patients with PAD., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Preventing the occurrence of cardiovascular disease (CVD) with nutritional interventions is a therapeutic strategy that may warrant greater research attention. The increased use of omega (ω)-3 fatty acids is a powerful example of one such nutritional strategy that may produce significant cardiovascular benefits. Marine food products have provided the traditional dietary sources of ω-3 fatty acids. Flaxseed is an alternative to marine products. It is one of the richest sources of the plant-based ω-3 fatty acid, alpha-linolenic acid (ALA). Based on the results of clinical trials, epidemiological investigations and experimental studies, ingestion of ALA has been suggested to have a positive impact on CVD. Because of its high ALA content, the use of flaxseed has been advocated to combat CVD. The purpose of the present review was to identify the known cardiovascular effects of flaxseed and ALA and, just as importantly, what is presently unknown.

Functional foods and nutraceuticals are becoming popular alternatives to pharmacological treatments by providing health benefits and (or) reducing the risk of chronic diseases. Flaxseed is a rich source of 3 components with demonstrated cardioprotective effects: the omega-3 fatty acid alpha-linolenic acid (ALA), dietary fibre, and phytoestrogen lignans. Multiple clinical dietary intervention trials report that consuming flaxseed daily can modestly reduce circulating total cholesterol (TC) by 6%-11% and low-density lipoprotein (LDL) cholesterol by 9%-18% in normolipemic humans and by 5%-17% for TC and 4%-10% for LDL cholesterol in hypercholesterolemic patients, as well as lower various markers associated with atherosclerotic cardiovascular disease in humans. Evidence to date suggests that the dietary fibre and (or) lignan content of flaxseed provides the hypocholesterolemic action. The omega-3 ALA found in the flaxseed oil fraction also contributes to the antiatherogenic effects of flaxseed via anti-inflammatory and antiproliferative mechanisms. Dietary flaxseed may also protect against ischemic heart disease by improving vascular relaxation responses and by inhibiting the incidence of ventricular fibrillation.

It is becoming increasingly evident that poor nutrition plays an important role in inducing cardiovascular disease. Just as importantly, data now support the contention that appropriate nutritional interventions may have just as important an effect in preventing or delaying the appearance of cardiovascular disease. If this is indeed true, then it is critical that these advances in our knowledge of the effects of nutritional interventions be translated into effective strategies to combat cardiovascular disease. It is argued in this paper, with a few specific examples, that the translation of nutritional interventions can provide powerful approaches to alleviating the clinical challenges currently facing us today in the cardiovascular field. Furthermore, the value-added economic advantages of translating nutritional strategies on a wide scale into the public become another intriguing argument to further support investigations in this growing field.

Objective: The impact of dietary polyunsaturated fatty acids (PUFAs) of the n-6 and n-3 series on the cardiovascular system is well documented. To directly compare the effects of three dietary oils (fish, flaxseed and hempseed) given in concentrations expected to be self-administered in the general population on specific cardiovascular parameters in healthy volunteers., Design: 86 healthy male and female volunteers completed a 12 week double blinded, placebo controlled, clinical trial. They were randomly assigned to one of the four groups. Subjects were orally supplemented with two 1 gm capsules of placebo, fish oil, flaxseed oil or hempseed oil per day for 12 weeks., Results: Plasma levels of the n-3 fatty acids docosahexanoic acid and eicosapentanoic acid increased after 3 months supplementation with fish oil. Alpha linolenic acid concentrations increased transiently after flaxseed supplementation. However, supplementation with hempseed oil did not significantly alter the concentration of any plasma fatty acid. The lipid parameters (TC, HDL-C, LDL-C and TG) did not show any significant differences among the four groups. Oxidative modification of LDL showed no increase in lag time over the 12 wk period. None of the dietary interventions induced any significant change in collagen or thrombin stimulated platelet aggregation and no increase in the level of inflammatory markers was observed., Conclusion: From a consumer's perspective, ingesting 2 capsules of any of these oils in an attempt to achieve cardiovascular health benefits may not provide the desired or expected result over a 3 month period.

Dietary conjugated linoleic acid (CLA) and the antihypertensive drug, telmisartan, have both been shown to modify cardiovascular risks. The effects of a combination of these two agents have, however, not been investigated. This 20 week study sought to assess the therapeutic potential of a CLA/telmisartan co-administration in rats fed a high-fructose high-fat diet. Thirty-three male Sprague-Dawley rats were randomly assigned to five experimental groups, including control, losartan, telmisartan, CLA, and CLA + telmisartan-treated animals. Body weight, blood pressure, and blood levels of lipids, glucose, insulin, and inflammatory markers were measured. Co-administration of CLA and telmisartan resulted in significant (P < 0.05) reductions in body weight, visceral fat, serum total cholesterol, triglycerides, glucose, plasma insulin concentrations, and systolic blood pressure compared with those in the control group. Moreover, plasma levels of IL1-alpha and IFN-gamma were reduced and levels of IL1-beta, IL-4, IL-6, and IL-10, plus TNF-alpha were increased in the co-therapy group, compared with controls. In conclusion, this study suggests that a combination of CLA with telmisartan may modify several risk factors of cardiovascular disease commonly seen in metabolic syndrome. This combination of nutraceuticals and pharmaceuticals may be a safe and cost-effective strategy in a number of high-risk subjects. Future studies will further document clinical benefits of such combination therapy.

Diabetes is a serious medical and financial burden on western societies. It is the seventh leading cause of death in the United States and Canada. The disease is due to a primary defect in glucose tolerance and carbohydrate metabolism resulting from either a deficiency of insulin (Insulin-dependent (type I) diabetes mellitus - IDDM) or a state of insulin resistance (Non-insulin-dependent (type II) diabetes mellitus - NIDDM). NIDDM comprises greater than 80% of total diabetic cases. Associated with the primary metabolic defects are equally deleterious secondary complications affecting the renal, ocular, nervous and cardiovascular systems. The cardiovascular complications account for a major proportion of diabetic mortality. As such, it is of paramount importance to develop or find an animal model expressing complications homologous to the human condition. Many models of NIDDM are available to the diabetic researcher but choosing an accurate one can be difficult. The following compares the advantages and limitations of one such model, the JCR:LA-cp rat to other NIDDM models commonly used today.

Low density lipoproteins have the capacity to alter cell calcium concentrations of a wide variety of cell types. The precise mechanism of physical interaction of the LDL or its products with the cell is not defined yet. There is more agreement about the calcium transport pathway affected. Most studies show an ability of LDL to alter transsarcolemmal calcium flux, probably through the slow calcium channel. However, internal stores of calcium like the sarcoplasmic reticulum also appear to be altered. These effects of LDL on cellular calcium homeostasis have potential importance in both physiological and disease settings. Oxidised LDL has even more potential significance than the native LDL in disease conditions. Free radical mediated oxidation of LDL during atherosclerotic and ischaemic conditions creates a molecule with even greater potency for altering cell calcium and ultimately cell function and viability. The interaction of this trio of compounds--LDL, free radicals, and cellular calcium--may be critical for the mechanism of pathogenesis in specific cardiovascular diseases. It will be important in the future to identify new therapeutic strategies to prevent their interaction.