Background: First responders (firefighters, paramedics, and police) working in an urban setting can be exposed to a high-stress environment caused by strenuous physical exertion, potentially dangerous work conditions, sleep deprivation due to shift work, poor dietary habits, psychological stress and noise levels that are excessive. This may induce chronic increases in blood pressure. The purpose of this study was to determine the presence of hypertension in people working in occupations generally accepted as high stress in comparison to those working in an environment where less of these obvious high stressors were present. Methods: Resting blood pressure was measured by TrUBP in 1067 on-duty first responders (fire, paramedic, and police), and in participants generally associated with a lower-stress work environment (transit workers, city and bank employees, factory workers and legislature employees). Results: The average age, systolic and diastolic blood pressures were significantly lower in those employees working in a high-stress environment than those in a low-stress job. This difference was observed in both male and female sexes. Conclusions: Our data do not support an association of high resting blood pressure values in those employed in activities typically associated with a high-stress urban working environment.

The response of heat shock proteins (HSPs) to stress-induced stimuli is now well documented and understood. Specific HSPs like HSP70 play an important role in vascular diseases like atherosclerosis and hypertension. However, the involvement of other HSPs in these vascular pathologies has been largely ignored. HSP60 plays a particularly critical role in vascular cell growth, an important component of many vascular pathologies. HSP60 directly induces vascular smooth muscle cell proliferation. The mechanism may involve an HSP60-induced stimulation of the rate of nuclear protein import in the smooth muscle cell. HSP60 expression levels also correlate with the severity of the disease. In conclusion, HSP60 may have an important role to play in vascular diseases like atherosclerosis. HSP60 may be a promising future pharmaceutical target to focus upon in order to deter the pathological effects of disease conditions like hypertension and atherosclerosis.

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.

Hypertension contributes to the increase in health care spending in Canada through two primary mechanisms. First, it directly increases costs, as individuals with hypertension require medical care to manage the condition. Second, it indirectly raises expenses by serving as a risk factor for numerous chronic diseases, leading to increased health care utilization among those affected. Therefore, reducing hypertension prevalence could alleviate its resulting strain on the Canadian health care system. Clinical trials have demonstrated that daily flaxseed consumption effectively lowers both systolic and diastolic blood pressure. This study employs a four-step cost-of-illness analysis to estimate the potential health care cost-savings from a flaxseed-based treatment for hypertension. The analysis begins by assessing the proportion of individuals with hypertension likely to adopt the flaxseed regimen. It then evaluates the impact of flaxseed consumption on systolic and diastolic blood pressure. Next, data from the Canadian Health Measures Survey, Cycles 5 and 6, are used to estimate the prevalence of hypertension and the expected reduction in prevalence due to the flaxseed treatment. Finally, the potential reduction in health care spending is calculated. To incorporate uncertainty, partial sensitivity analysis and Monte Carlo simulations were utilized, varying the intake success rate and other model parameters, respectively. The most conservative estimate suggests a potential health care cost-savings of CAD 96,284,344 in Canada for the year 2020.

Introduction: Stroke is the second leading cause of death worldwide and the leading cause of disability. Without a plasma biomarker care is often delayed. The brain is rich in lipids, which readily cross the blood-brain barrier, and therefore represent a target for biomarkers of stroke. The study aimed to determine the lipidomic changes in plasma in stroke patients through an untargeted and targeted analysis. Methods: A cohort of 482 patients from the INTERSTROKE study was included in the analysis. This included 241 stroke patients (120 ISCH, 121 HEM) and 241 age and sex-matched controls. A LC/MS/MS platform was used to perform a detailed lipidomic and oxylipidomic analysis of plasma. Biomarker analysis was performed using the Random Forest Classification algorithm (RFC). Results: Lipidomic analysis identified 141 lipid species and 32 oxylipins significantly altered in ISCH stroke compared to control and 167 lipid species and 34 oxylipins in HEM stroke. Between ISCH and HEM stroke there were in 87 significant lipids. There was a 141 % increase in phosphatidylserine (PS) 40:6 (p< 0.0001) in patients with HEM stroke compared to ISCH, whereas prostaglandin E2 was found to be 94% higher (p<0.0001) in ISCH stroke. RFC model identified lysophosphatidylcholine (LPC) 14:0 and 15-oxoETE as the most important features contributing to classification between control and stroke with a mean AUC score of 0.81 and 0.69 respectively. PS 40:6 and 14-HDoHE are the most important features contributing to separating ISCH and HEM stroke, with mean AUC scores of 0.84 and 0.67, respectively. PC 34:1 and PC-O 36:3 were found to be the biggest predictors of stroke outcomes at 30 days, measured by The Modified Rankin Score (mRS) score. In addition, four lipids: Ceramide 24:1, C14 Tetradecanoyl Carnitine, trihexosylceramide 16:0, and PS 40:6 were found to be the independent predictors of mortality in patients with stroke. Conclusion: We have demonstrated significant alterations in the human plasma lipidome during acute stroke, revealing distinct differences between HEM and ISCH subtypes. These lipid profiles not only differentiate between stroke subtypes but also predict clinical outcomes. Given the current lack of plasma biomarkers for stroke, our study underscores the potential of lipid molecules as valuable biomarkers for stroke diagnosis and prognosis.

Non-alcoholic fatty liver disease (NAFLD), a significant cause of chronic liver disease, presents a considerable public health concern. Despite this, there is currently no treatment available. This study aimed to investigate dietary flaxseed in the JCR:LA-corpulent rat strain model of NAFLD. Both obese male and female rats were studied along with their lean counterparts after 12 weeks of ingestion of a control diet, or control diet with flaxseed, or high fat, high sucrose (HFHS), or HFHS plus flaxseed. Obese rats showed higher liver weight and increased levels of cholesterol, triglyceride, and saturated fatty acid, which were further elevated in rats on the HFHS diet. The HFHS diet induced a significant two-fold elevation in the plasma levels of both aspartate aminotransferase and alanine aminotransferase in the obese male and female rats. Including flaxseed in the HFHS diet significantly lowered liver weight, depressed the plasma levels of both enzymes in the obese male rats, and reduced hepatic cholesterol and triglyceride content as well as improving the fatty acid profile. In summary, including flaxseed in the diet of male and female obese rats led to an improved lipid composition in the liver and significantly reduced biomarkers of tissue injury despite consuming a HFHS chow.

It is arguable that nutritional research is as exciting and important as gene or cell-based therapies with regard to its potential to treat and prevent cardiovascular disease. Long-chain omega-3 polyunsaturated fatty acids have a significant impact on cardiovascular disease and although the effects are most commonly associated with fish-derived sources, plant sources also provide important omega-3 polyunsaturated fatty acids that have a proven capacity to alter cardiovascular disease. This chapter will review our current knowledge about two excellent plant sources of omega-3 polyunsaturated fats (PUFAs), hempseed, and flaxseed, and will compare them with respect to their impact on cardiovascular disease.

The inclusion of flaxseed in the diet may have a great number of potential benefits for the well-being of both healthy individuals and those challenged by disease conditions as well. With an increase in the number and quality of studies focused on the physiological and pathophysiological effects of dietary flaxseed, our knowledge concerning the rationale for the inclusion of flaxseed in our diet has become more convincing and stronger. The purpose of this review is threefold. First, the review will comprehensively document the evidence supporting the value of dietary flaxseed to improve bodily health in both normal and disease conditions. Second, this review will identify the mechanisms of action responsible for these effects. Finally, this article will review practical aspects relevant to the inclusion of flaxseed in the diet. Briefly, supplementing the diet with flaxseed has beneficial effects on the treatment and/or prevention of different kinds of cardiovascular disease (hypertension, ischemic heart disease, myocardial infarcts, atherosclerosis), non-alcoholic fatty liver disease, breast cancer, bone strength, menopause, diabetes, and wound healing. Although some controversy exists on the component within flaxseed that provides these beneficial actions, it is likely that the rich content of the omega-3 fatty acid, alpha linolenic acid, is primarily responsible for the majority of these biological effects. It is concluded that the constantly expanding evidence in support of the inclusion of flaxseed in our daily diet to provide significant health benefits strongly encourages the initiation of additional work on dietary flaxseed in order to both confirm past findings as well as to further advance our knowledge regarding the important biological actions of dietary flaxseed.

The mammalian Na+/H+ exchanger (NHE) is a family of ubiquitous membrane proteins present in humans. Isoform one (NHE1) is present on the plasma membrane and regulates intracellular pH by removal of one intracellular proton in exchange for one extracellular sodium thus functioning as an electroneutral process. Human NHE1 has a 500 amino acid membrane domain plus a C-terminal 315 amino acid, regulatory cytosolic tail. It is regulated through a cytosolic regulatory C-terminal tail which is subject to phosphorylation and is modulated by proteins and lipids. Substantial evidence has implicated NHE1 activity in both myocardial ischemia and reperfusion damage and myocardial remodeling resulting in heart failure. Experimental data show excellent cardioprotection with NHE1 inhibitors although results from clinical results have been mixed. In cardiac surgery patients receiving the NHE1 inhibitor cariporide, subgroups showed beneficial effects of treatment. However, in one trial this was associated with a significantly increased incidence of ischemic strokes. This likely reflected both inappropriate dosing regimens as well as overly high drug doses. We suggest that further progress towards NHE1 inhibition as a treatment for cardiovascular disease is warranted through the development of novel compounds to inhibit NHE1 that are structurally different than those previously used in compromised clinical trials. Some novel pyrazinoyl guanidine inhibitors of NHE1 are already in development and the recent elucidation of the three-dimensional structure of the NHE1 protein and identity of the inhibitor binding site may facilitate development. An alternative approach may also be to control the endogenous regulation of activity of NHE1, which is activated in disease.

Inflammation plays a critical role in atherosclerosis and cardiovascular disease. Bacteria and viruses are major causative agents of inflammation in the body which normally develops as a response to infection. It is a logical extention, therefore, to believe bacterial and viral infections may be involved in a variety of presentations of cardiovascular diseases. The purpose of this review is to describe the data and conclusions to date on the involvement of these infectious agents in the induction of cardiovascular disease. The review also discusses the various specific bacteria and viruses that have been implicated in cardiovascular disease and the mechanisms, if known, that these agents induce cardiovascular disease.

Peripheral artery disease (PAD) is prevalent among individuals with a history of tobacco smoking. Although oxidation of lipids may contribute to atherogenesis in vascular disease, enzymatically and nonenzymatically produced oxidized lipids can have varying and contrasting physiological effects. The underlying mechanisms of atherogenic vulnerability can be better elucidated with the recent advances in oxylipidome quantification using HPLC-MS/MS technology. In a randomized, controlled clinical trial, the plasma oxylipidome was analyzed in participants living with PAD by smoking status (n = 98) and in nonsmoking comparators without chronic disease (n = 20). Individuals with PAD had approximately a four-fold higher level of total plasma oxylipins versus the comparator. Cessation of smoking in individuals with PAD was associated with significantly lower levels of linoleic acid-derived TriHOMEs, greater levels of omega-3 fatty acid-derived oxylipins, and greater levels of nonfragmented oxidized phosphatidylcholines (OxPCs). Individuals living with PAD but without a history of smoking, exhibited higher levels of the putative atherogenic fragmented OxPCs versus individuals who currently or previously smoked. These data implicate the plasma oxylipidome in PAD and that smoking cessation is associated with a less inflammatory profile. Furthermore, fragmented OxPCs may play a more significant role in the pathophysiology of PAD in individuals without a history of smoking.

Invasive cardiovascular procedures which include heart transplantations, congenital heart surgery, coronary artery bypass grafts, cardiac valve repair and replacement, and interventional cardiac electrophysiology procedures represent common mechanisms to treat a variety of cardiovascular diseases across the globe. The majority of these invasive approaches employ antibiotics as a regular and obligatory feature of the invasive procedure. Although the growing incidence of bacterial resistance to currently used antibiotics threatens to curtail the use of all interventional surgical techniques, it remains an underappreciated threat within the arsenal of cardiovascular therapies. It is reasonable to expect that the continued overuse of antibiotics and the frequent management of coronavirus disease 2019 (COVID-19) infected patients with high doses of antibiotics will inevitably accentuate the rise of multidrug resistance. The purpose of this article is to heighten awareness of the role of bacterial infections in cardiovascular disease, the use of antibiotics in today's cardiovascular surgical theaters, the threat facing cardiovascular surgery should multidrug resistance continue to rise unabated, and the development of new antibiotic platforms to solve this problem.

This white paper summarizes the key outcomes, topics, and recommendations from the Canada-India Healthcare Summit 2021 Conference, Biotechnology Session, held on May 20–21, 2021. In particular, the authors have focused their attention on topics ranging from research and development into the etiology and treatment of COVID-19 to novel approaches, such as ultraviolet-C disinfection and cell and gene therapy. The paper also deals with important topics around the effects of food distribution and nutrition on COVID-19 and vice versa, as well as key considerations around research and development, innovation, policy, grants, and incentives, and finally, summarizes the ways in which Canada and India, being close allies, have already begun to partner to fight the pandemic (as well as future strategies to continue this excellent progress). We also include key points raised during the summit and summarize them as part of this white paper.

There is an increased interest in the gut microbiota as it relates to health and obesity. The impact of diet and sex on the gut microbiota in conjunction with obesity also demands extensive systemic investigation. Thus, the influence of sex, diet, and flaxseed supplementation on the gut microbiota was examined in the JCR:LA-cp rat model of genetic obesity. Male and female obese rats were randomized into four groups (n = 8) to receive, for 12 weeks, either (a) control diet (Con), (b) control diet supplemented with 10% ground flaxseed (CFlax), (c) a high-fat, high sucrose (HFHS) diet, or (d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. Illumine MiSeq sequencing revealed a richer microbiota in rats fed control diets rather than HFHS diets. Obese female rats had lower alpha-diversity than lean female; however, both sexes of obese and lean JCR rats differed significantly in β-diversity, as their gut microbiota was composed of different abundances of bacterial types. The feeding of an HFHS diet affected the diversity by increasing the phylum Bacteroidetes and reducing bacterial species from phylum Firmicutes. Fecal short-chain fatty acids such as acetate, propionate, and butyrate-producing bacterial species were correspondingly impacted by the HFHS diet. Flax supplementation improved the gut microbiota by decreasing the abundance of Blautia and Eubacterium dolichum. Collectively, our data show that an HFHS diet results in gut microbiota dysbiosis in a sex-dependent manner. Flaxseed supplementation to the diet had a significant impact on gut microbiota diversity under both flax control and HFHS dietary conditions.

Previous work has shown that dietary flaxseed can significantly reduce cardiac damage from a coronary artery ligation-induced myocardial infarction. However, this model uses healthy animals and the ligation creates the infarct in an artificial manner. The purpose of this study was to determine if dietary flaxseed can protect the hearts of JCR:LA-cp rats, a model of genetic obesity and metabolic syndrome, from naturally occurring myocardial ischemic lesions. Male and female obese rats were randomized into four groups (n = 8 each) to receive, for 12 weeks, either a) control diet (Con), b) control diet supplemented with 10% ground flaxseed (CFlax), c) a high-fat, high sucrose (HFHS) diet, or d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. In male obese rats, serum total cholesterol and LDL-C were significantly lower in CFlax compared to Con.  Obese rats on HFHS exhibited increased myocardial ischemic lesions and diastolic dysfunction regardless of sex. HFlax significantly lowered the frequency of cardiac lesions and improved diastolic function in male and female obese rats compared to HFHS. Blood pressures were similar in obese and lean rats. No aortic atherosclerotic lesions were detectable in any group. Collectively, this study shows that a HFHS diet increased myocardial ischemic lesion frequency and abolished the protective effect of female sex on cardiac function. More importantly, the data demonstrates dietary flaxseed protected against the development of small spontaneous cardiac infarcts despite the ingestion of a HFHS diet and the presence of morbid obesity.

Introduction: Myocardial ischemia/reperfusion injury (IRI) results in additional myocardial cell loss post reperfusion. Oxidized phosphocholine(PC)-containing phospholipids (OxPL) have been shown to result in cardiomyocyte cell death during IRI. E06 is a natural murine monoclonal IgM antibody which binds to the PC headgroup of OxPL. Transgenic mice expressing a single-chain Fv E06 fragment have recently been shown to have smaller infarct sizes post myocardial IRI. The objective of this study was to determine if directly infused E06 IgM reduced IRI in a porcine model of reperfusion injury that more closely reflects human physiology. Methods: Male pigs, 45 to 50 kg, were randomized equally to IRI in two groups: 1) control with saline coronary infusion (n=7). 2) IgM E06 coronary infusion over 1 hour (n=7). The left anterior descending (LAD) artery was occluded distal to the second diagonal branch for 60 minutes using an angioplasty balloon. Following balloon deflation, saline or IgM E06 was infused over 60 min through a microcatheter. Following 120 min of total reperfusion, the area at risk (AAR) and infarct size (IS) were determined by triphenyltetrazolium chloride staining technique (TTC), and myocardial salvage index determined. Results: All animals survived post reperfusion and no differences were present in hemodynamics at the baseline and 2 h post reperfusion between groups. A 51.3% reduction in infarct size was noted in animals receiving intracoronary E06 compared to controls (IS/AAR 21.7% ± 3.4 vs 42.3% ± 3.7 p<0.0005). IS/LV size (7.7 ± 3.2 vs 11.9 ± 1.2 p<0.004) and myocardial salvage index (82.6% vs 57.6% in controls) were significantly improved in animals receiving E06 compared to controls. Conclusion: Intracoronary delivery of E06 antibody at the time of reperfusion leads to a significant reduction in infarct size, suggesting that generation of OxPL during reperfusion leads to cardiomyocyte cell death. Translation of this approach using humanized anti-OxPL antibodies may allow a novel approach to treat myocardial IRI in humans.

The coronavirus disease 2019 (COVID-19) pandemic has had significant morbidity, mortality, social and financial implications for the global population. Despite this knowledge, we still know very little about how COVID-19 infection affects quality of life resulting from changes in nutritional behaviour and, conversely, how nutrition could modulate the epidemiology of COVID-19. In addition, the social isolation most have experienced due to the regulations imposed by governments during the COVID-19 pandemic may have also had effects on our nutritional behaviour. It is possible that nutritional interventions may have effects on the incidence of COVID-19 infection and mortality rates. The purpose of this review is to evaluate the current status of research on the topic of nutrition as it relates to the COVID-19 pandemic.

Myocardial ischemia-reperfusion (I/R) injury increases the generation of oxidized phosphatidylcholines (OxPCs), which results in cell death. However, the mechanism by which OxPCs mediate cell death and cardiac dysfunction is largely unknown. The aim of this study was to determine the mechanisms by which OxPC triggers cardiomyocyte cell death during reperfusion injury. Adult rat ventricular cardiomyocytes were treated with increasing concentrations of various purified fragmented OxPCs. Cardiomyocyte viability, bioenergetic response, and calcium transients were determined in the presence of OxPCs. Five different fragmented OxPCs resulted in a decrease in cell viability, with 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-(9'-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PONPC) having the most potent cardiotoxic effect in both a concentration and time dependent manner (P < 0.05). POVPC and PONPC also caused a significant decrease in Ca2+ transients and net contraction in isolated cardiomyocytes compared to vehicle treated control cells (P < 0.05). PONPC depressed maximal respiration rate (P < 0.01; 54%) and spare respiratory capacity (P < 0.01; 54.5%). Notably, neither caspase 3 activation or TUNEL staining was observed in cells treated with either POVPC or PONPC. Further, cardiac myocytes treated with OxPCs were indistinguishable from vehicle-treated control cells with respect to nuclear high-mobility group box protein 1 (HMGBP1) activity. However, glutathione peroxidase 4 activity was markedly suppressed in cardiomyocytes treated with POVPC and PONPC coincident with increased ferroptosis. Importantly, cell death induced by OxPCs could be suppressed by E06 Ab, directed against OxPCs or by ferrostatin-1, which bound the sn-2 aldehyde of POVPC during I/R. The findings of the present study demonstrate that oxidation of phosphatidylcholines during I/R generate bioactive phospholipid intermediates that disrupt mitochondrial bioenergetics and calcium transients and provoke wide spread cell death through ferroptosis. Neutralization of OxPC with E06 or with ferrostatin-1 prevents cell death during reperfusion. Our study demonstrates a novel signaling pathway that operationally links generation of OxPC during cardiac I/R to ferroptosis. Interventions designed to target OxPCs may prove beneficial in mitigating ferroptosis during I/R injury in individuals with ischemic heart disease.NEW & NOTEWORTHY Oxidized phosphatidylcholines (OxPC) generated during reperfusion injury are potent inducers of cardiomyocyte death. Our studies have shown that OxPCs exert this effect through a ferroptotic process that can be attenuated. A better understanding of the OxPC cell death pathway can prove a novel strategy for prevention of cell death during myocardial reperfusion injury.

Despite advances in diagnostic, prognostic, and treatment modalities, myocardial infarction (MI) remains a leading cause of morbidity and mortality. Impaired cellular signaling after an MI causes maladaptive changes resulting in cardiac remodeling. MicroRNAs (miRNAs/miR) along with other molecular components have been investigated for their involvement in cellular signaling in the pathogenesis of various cardiac conditions like MI. miRNAs are small non-coding RNAs that negatively regulate gene expression. They bind to complementary mRNAs and regulate the rate of protein synthesis by altering the stability of their targeted mRNAs. A single miRNA can modulate several cellular signaling pathways by targeting hundreds of mRNAs. This review focuses on the biogenesis and beneficial effects of cellular and circulating (exosomal) miRNAs on cardiac remodeling after an MI. Particularly, miR-1, -133, 135, and -29 that play an essential role in cardiac remodeling after an MI are described in detail. The limitations that will need to be addressed in the future for the further development of miRNA-based therapeutics for cardiovascular conditions will also be discussed.