Nutrition and Cardiovascular Health

There is unequivocal experimental, epidemiological and clinical evidence demonstrating a correlation between diet and increased risk of cardiovascular disease (CVD) [...

Mechanisms for the Defects in Phospholipid Signal Transduction in Diabetic Cardiomyopathy

431-440Although diabetic cardiomyopathy is associated with heart dysfunction and disturbance in cardiac sarcolemmal membrane phospholipid composition, the role of the different phospholipases and their related signaling mechanisms to altered function of the heart in diabetes is not completely understood. Thus, understanding the pathophysiology of cardiovascular abnormalities in diabetes, as well as identifying defects in various components of the phospholipid signaling pathways, that could serve as therapeutic targets, is warranted. Accordingly, this review provides an outline of the role of and the mechanisms for the defects in phospholipase A2, C and D-mediated signal transduction in the diabetic heart. In addition, the potential of different phospholipases as targets for drug development for the prevention/treatment of heart disease in diabetes is discussed. </span

Modification of gene expression in rat cardiomyocytes by linoleic and docosahexaenoic acid

Regulation of cardiac fatty acid metabolism is central to the development of cardiac hypertrophy and heart failure. We investigated the effects of some specific fatty acids on the expression of genes involved in immediate early as well as inflammatory and hypertrophic responses in adult rat cardiomyocytes. Cardiac remodeling begins with upregulation of immediate early genes c-fos and c-jun, followed by upregulation of inflammatory genes such as NF-kB and NFAT. At later stages, genes involved in the hypertrophic responses such as atrial natriuretic peptide (ANP) and brain natriuretic factor (BNF) are upregulated. Adult rat cardiomyocytes were treated with saturated fatty acid palmitic acid, monounsaturated fatty acid oleic acid, polyunsaturated fatty acids (PUFA) belonging to the n-6 class, linoleic acid and n-3 PUFA docosahexaenoic acid. Linoleic acid produced a greater increase in the mRNA expression of c-fos, c-jun, NF-ÎşB, NFAT3, ANP and BNP, in comparison to palmitic acid and oleic acid. In contrast, docosahexaenoic acid caused a decrease in the expression of genes involved in cardiac hypertrophy. Our findings suggest that linoleic acid is a potent inducer of cardiac hypertrophy, whereas docosahexaenoic acid exerts protective effects for heart health benefits.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Role of Oxidative Stress in Metabolic and Subcellular Abnormalities in Diabetic Cardiomyopathy

Although the presence of cardiac dysfunction and cardiomyopathy in chronic diabetes has been recognized, the pathophysiology of diabetes-induced metabolic and subcellular changes as well as the therapeutic approaches for the prevention of diabetic cardiomyopathy are not fully understood. Cardiac dysfunction in chronic diabetes has been shown to be associated with Ca2+-handling abnormalities, increase in the availability of intracellular free Ca2+ and impaired sensitivity of myofibrils to Ca2+. Metabolic derangements, including depressed high-energy phosphate stores due to insulin deficiency or insulin resistance, as well as hormone imbalance and ultrastructural alterations, are also known to occur in the diabetic heart. It is pointed out that the activation of the sympathetic nervous system and renin&ndash;angiotensin system generates oxidative stress, which produces defects in subcellular organelles including sarcolemma, sarcoplasmic reticulum and myofibrils. Such subcellular remodeling plays a critical role in the pathogenesis of diabetic cardiomyopathy. In fact, blockade of the effects of neurohormonal systems has been observed to attenuate oxidative stress and occurrence of subcellular remodeling as well as metabolic abnormalities in the diabetic heart. This review is intended to describe some of the subcellular and metabolic changes that result in cardiac dysfunction in chronic diabetes. In addition, the therapeutic values of some pharmacological, metabolic and antioxidant interventions will be discussed. It is proposed that a combination therapy employing some metabolic agents or antioxidants with insulin may constitute an efficacious approach for the prevention of diabetic cardiomyopathy

Modification of Ischemia/Reperfusion-Induced Alterations in Subcellular Organelles by Ischemic Preconditioning

It is now well established that ischemia/reperfusion (I/R) injury is associated with the compromised recovery of cardiac contractile function. Such an adverse effect of I/R injury in the heart is attributed to the development of oxidative stress and intracellular Ca2+-overload, which are known to induce remodeling of subcellular organelles such as sarcolemma, sarcoplasmic reticulum, mitochondria and myofibrils. However, repeated episodes of brief periods of ischemia followed by reperfusion or ischemic preconditioning (IP) have been shown to improve cardiac function and exert cardioprotective actions against the adverse effects of prolonged I/R injury. This protective action of IP in attenuating myocardial damage and subcellular remodeling is likely to be due to marked reductions in the occurrence of oxidative stress and intracellular Ca2+-overload in cardiomyocytes. In addition, the beneficial actions of IP have been attributed to the depression of proteolytic activities and inflammatory levels of cytokines as well as the activation of the nuclear factor erythroid factor 2-mediated signal transduction pathway. Accordingly, this review is intended to describe some of the changes in subcellular organelles, which are induced in cardiomyocytes by I/R for the occurrence of oxidative stress and intracellular Ca2+-overload and highlight some of the mechanisms for explaining the cardioprotective effects of IP

Susceptibility of Diabetic Heart to Catecholamine-induced Arrhythmias is Independent of Contractile Dysfunction

Uvod: Dijabetes je udružen sa električnom nestabilnošću miokarda i produženim trajanjem akcionog potencijala što rezultuje poremećajima srčanog ritma. Cilj: Ova studija je sprovedena sa ciljem da ispita ulogu cirkulišućih kateholamina kod poremećaja srčanog ritma i kontraktilnosti miokarda tokom različitih stadijuma dijabetesa. Metode: Kod muških pacova soja Sprague - Dawley dijabetes je izazvan streptozocinom (STZ; 65 mg/kg, i.v.). Aritmije izazvane adrenalinom (4 - 128 μg/kg, i.v.) i koncentracija adrenalina i noradrenalina detektovane su u kontrolnoj grupi i nakon 4. i 8. nedelje kod životinja kojima je indukovan dijabetes. Remodelovanje srca kao i kontraktilna funkcija su procenjene ehokardiografi jom. Rezultati: Iako je dijabetes izazvao poremećaj srčane funkcije, nije bilo značajnijih razlika u udarnom volumenu, ejekcionoj frakciji, dimenzijama leve komore, frakcionom skraćenju leve komore između životinja koje imaju dijabetes 4 i 8 nedelja. Elektrokardiogram obe grupe životinja sa dijabetesom pokazao je duboki S talas i promene u T talasu i ST segmentu. Pored toga, došlo je do produženja RR intervala kod životinja koje imaju dijabetes 4 i 8 nedelja, dok se produženje QT i PR intervala javilo samo kod životinja koje imaju dijabetes 8 nedelja. Opasnost od ventikularnih aritmija izazvanih adrenalinom, koja se procenjuje pomoću aritmija skora, bila je značajno niža kod životinja koje imaju dijabetes 8 nedelja u poređenju sa životinjama koje imaju dijabetes 4 nedelje. Nivoi cirkulišućeg adrenalina su bili značajno niži kod životinja koje imaju dijabetes 8 nedelja, dok su nivoi noradrenalina bili povišeni kod životinja koje imaju dijabetes 4 nedelje. Zaključak: Osetljivost dijabetičnog srca na aritmije izazvane kateholaminima može zavisiti više od koncentracije cirkulišuceg adrenalina nego od koncentracije noradrenalina, zbog čega se može pretpostaviti da povećana incidenca iznenadnih srčanih smrti u dijabetesu ne mora biti povezana sa odgovorom na kateholamine

Metabolomic Fingerprinting for the Detection of Early-Stage Lung Cancer: From the Genome to the Metabolome

The five-year survival rate of lung cancer patients is very low, mainly because most newly diagnosed patients present with locally advanced or metastatic disease. Therefore, early diagnosis is key to the successful treatment and management of lung cancer. Unfortunately, early detection methods of lung cancer are not ideal. In this brief review, we described early detection methods such as chest X-rays followed by bronchoscopy, sputum analysis followed by cytological analysis, and low-dose computed tomography (LDCT). In addition, we discussed the potential of metabolomic fingerprinting, compared to that of other biomarkers, including molecular targets, as a low-cost, high-throughput blood-based test that is both feasible and affordable for early-stage lung cancer screening of at-risk populations. Accordingly, we proposed a paradigm shift to metabolomics as an alternative to molecular and proteomic-based markers in lung cancer screening, which will enable blood-based routine testing and be accessible to those patients at the highest risk for lung cancer.Medicine, Faculty ofNon UBCInfectious Diseases, Division ofMedicine, Department ofReviewedFacultyResearche