Integrins and cardiovascular disease

Cardiovascular diseases involve abnormal cell-cell interactions leading to the development of atherosclerotic plaque, which when ruptured causes massive platelet activation and thrombus formation. Parts of a loose thrombus may detach to form an embolus, blocking circulation at a more distant point. The integrins are a family of adhesive cell receptors interacting with adhesive proteins or with counterreceptors on other cells. There is now solid evidence that the major integrin on platelets, the fibrinogen receptor α _IIb  β ₃ , has an important role in several aspects of cardiovascular diseases and that its regulated inhibition leads to a reduction in incidence and mortality due to these disorders. The development of α _IIb  β ₃ inhibitors is an important strategy of many pharmaceutical companies which foresee a large market for the treatment of acute conditions in surgery, the symptoms of chronic conditions and, it is hoped, maybe even the successful prophylaxis of these conditions. Although all the associated problems have not been solved, the undoubted improvements in patient care resulting from the first of these treatments in the clinic have stimulated further research on the role of integrins on other vascular cells in these processes and in the search for new inhibitors. Both the development of specific inhibitors and of mice with specific integrin subunit genes ablated have contributed to a better understanding of the function of integrins in development of the cardiovascular system.     

The separation of fatty acids

Résumé Le problème de la séparation des acides gras est exposé en détail. Les méthodes physiques couramment appliquées à une macro- ou micro-échelle sont discutées et l'on donne des exemples tirés de la littérature ou de méthodes récemment utilisées dans les recherches. Celles-ci comprennent la cristallisation, la distillation fractionnée, la distribution par contre-courant, la chromatographie en phase gazeuse et la spectrographie de masse.

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Presented before the symposium on Chemistry and Physiology of Fats at the meeting of the Chemical Institute of Canada, Ottawa, October 9, 1957. Hormel Institute publication No. 168.     

Carotid occlusion and renal vein free fatty acids

Résumé L'occlusion de la carotide, l'épuisement du sodium du plasma et l'effet de la pression de perfusion rénale ont été utilisés pour étudier les niveaux d'acide gras non-estérifié dans la veine rénale. Dans la présente recherche, le système nerveux sympathique controlait la libération vers les reins de l'acide gras non-estérifié. Apparemment, l'épuisement du sodium n'affecte pas les niveaux normaux de repos de cet acide dans la veine rénale.

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A. W. Taylor is the recipient of a Research Associateship from the Department of National Health and Welfare, Ottawa.     

Regulation of SNARE fusion machinery by fatty acids

Vesicle fusion is a ubiquitous biological process involved in membrane trafficking and a variety of specialised events such as exocytosis and neurite outgrowth. The energy to drive biological membrane fusion is provided by fusion proteins called SNAREs. Indeed, SNARE proteins play critical roles in neuronal development as well as neurotransmitter and hormone release. SNARE proteins form a very tight alpha-helical bundle that can pull two membranes together, thereby initiating fusion. Whereas a great deal of attention has been paid to partner proteins that can affect SNARE function, recent genetic and biochemical evidence suggests that local lipid environment may be as important in SNARE regulation. Direct lipid modification of SNARE fusion proteins and their regulation by fatty acids following phospholipase action will be discussed here in detail. Our analysis highlights the fact that lipids are not a passive platform in vesicle fusion but intimately regulate SNARE function. Received 20 December 2006; received after revision 6 February 2007; accepted 15 March 2007     

Human skin-surface lipid fatty acids — Mosquito repellents

Résumé On a découvert que les lipides de l'épiderme humain sont répulsifs pour la femelled'Aedes aegypti. Cet effet est dû en partie à la présence d'acides gras non saturés. Les acides gras saturés ne contribuent pas à cette action.     

Essential fatty acids (EFA) deficiency and liver mitochondria

Summary 2 dietary fats, namely, hydrogenated coconut oil and safflower seed oil were fed at 20% levels to weanling male albino rats for a period of 2 months after which the animals were sacrificed and oxidative phosphorylation measured in liver mitochondria. This ratio was more in the unsaturated-fat-fed group of rats compared to the saturated-fed ones for glutamate and malate; in the case of succinate no such change was noticed.     

The effect of colchicine on plasma unesterified fatty acids

Zusammenfassung Die Verabereichung einer letalen Dosis Colchicin verursacht u. a. eine Zunahme der unveresterten Fettsäuren und eine Abnahme des Körpergewichts. Der Gehalt an veresterten Fettsäuren, freiem und verestertem Cholesterin und Plasmaeiweissen bleibt unverändert, ebenso Hämatokrit-und Hämoglobinwerte.

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Supported by the National Heart Institute, Bethesda, Md.     

Unsaturated fatty acids; platelet-serotonin releasers in tissue extract

Zusammenfassung Der Hauptanteil Serotonin freisetzenden Materials in alkalischen Gewebsextrakten erweist sich als ein Gemisch ungesättigter Fettsäuren, welche die Anregung der Serotoninausschüttung von Blutplättchen bewirken.     

Chloroplast aging in vitro and relationships to fatty acids and polyphenoloxidase activity

Résumé Un vieillissement in vitro de chloroplastes isolés d'épinard et un traitement par l'acide linolénique, à des concentrations croissantes, provoquent des inhibitions, comparables, de la photophosphorylation, de la capacité des plastides à se contracter et à dégager de l'O₂. De plus, ces deux traitements stimulent dans la même proportion l'activité des polyphénoloxydases. Ainsi, l'acide linolénique semble être l'un des facteurs responsables du vieillissement in vitro des chloroplastes.     

Liver X receptors in cardiovascular and metabolic disease

Liver X receptors (LXRs) α and β are nuclear oxysterol receptors and metabolic sensors initially found to regulate cholesterol metabolism and lipid biosynthesis. Recent studies have elucidated the importance of LXR in the development of cardiovascular diseases and metabolic disorders. LXR agonists prevent development of atherosclerosis by modulation of metabolic as well as inflammatory gene expression in rodent models. Moreover, LXR activation inhibits hepatic gluconeogenesis and lowers serum glucose levels, indicating possible application of LXR activation in the treatment of diabetes mellitus. However, first-generation LXR agonists elevate hepatic and serum trigylceride levels, making subtype-specific agonists and selective LXR modulators rather than unselective LXR agonists a potential pharmacological strategy. This review summarizes the multiple physiological and pathophysiological implications of LXRs and observations that identify LXRs as potential targets for therapeutic interventions in human cardiovascular and metabolic disease. Received 30 August 2005; received after revision 10 October 2005; accepted 4 November 2005