Platelet-activating factor and cardiac diseases: therapeutic potential for PAF inhibitors

Feuerstein, Giora; Rabinovici, Reuven; Leor, Jonathan; Winkles, James D.; Vonhof, Stefan

doi:10.1016/s0929-7855(96)00562-7

Cited by 29 publications

(25 citation statements)

References 121 publications

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“…Besides cardiomyocytes, several cellular elements within the myocardium, such as vascular endothelial cells and resident mast cells, have been shown to be capable of producing PAF. Therefore, the heart itself may be a source of PAF independently from inflammatory cells (13,30,40).…”

Section: Discussionmentioning

confidence: 99%

Platelet-activating factor induces cardioprotection in isolated rat heart akin to ischemic preconditioning: role of phosphoinositide 3-kinase and protein kinase C activation

Penna

Alloatti

Cappello³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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. Platelet-activating factor induces cardioprotection in isolated rat heart akin to ischemic preconditioning: role of phosphoinositide 3-kinase and protein kinase C activation. Am J Physiol Heart Circ Physiol 288: H2512-H2520, 2005. First published January 6, 2005; doi:10.1152/ajpheart.00599.2004.-Ischemic preconditioning (IP) is a cardioprotective mechanism against myocellular death and cardiac dysfunction resulting from reperfusion of the ischemic heart. At present, the precise list of mediators involved in IP and the pathways of their mechanisms of action are not completely known. The aim of the present study was to investigate the role of platelet-activating factor (PAF), a phospholipid mediator that is known to be released by the ischemic-reperfused heart, as a possible endogenous agent involved in IP. Experiments were performed on Langendorff-perfused rat hearts undergoing 30 min of ischemia followed by 2 h of reperfusion. Treatment with a low concentration of PAF (2 ϫ 10 Ϫ11 M) before ischemia reduced the extension of infarct size and improved the recovery of left ventricular developed pressure during reperfusion. The cardioprotective effect of PAF was comparable to that observed in hearts in which IP was induced by three brief (3 min) periods of ischemia separated by 5-min reperfusion intervals. The PAF receptor antagonist WEB-2170 (1 ϫ 10 Ϫ9 M) abrogated the cardioprotective effect induced by both PAF and IP. The protein kinase C (PKC) inhibitor chelerythrine (5 ϫ 10 Ϫ6 M) or the phosphoinositide 3-kinase (PI3K) inhibitor LY-294002 (5 ϫ 10 Ϫ5 M) also reduced the cardioprotective effect of PAF. Western blot analysis revealed that following IP treatment or PAF infusion, the phosphorylation of PKC-⑀ and Akt (the downstream target of PI3K) was higher than that in control hearts. The present data indicate that exogenous applications of low quantities of PAF induce a cardioprotective effect through PI3K and PKC activation, similar to that afforded by IP. Moreover, the study suggests that endogenous release of PAF, induced by brief periods of ischemia and reperfusion, may participate to the triggering of the IP of the heart. ischemia-reperfusion; WEB-2170; LY-294002 ISCHEMIC PRECONDITIONING (IP) is the phenomenon whereby brief periods of ischemia and reperfusion increase the resistance to myocardial infarction and contractile dysfunction induced by a subsequent sustained episode of ischemia (9, 34 -36). In all species tested, the beneficial effects of IP include protection against necrotic and apoptotic cell death. In some species, it has been shown that IP also induces the prevention of ischemia-reperfusion-induced arrhythmias, a faster recovery from reperfusion-induced myocardial stunning, and a protection of microvasculature function (for reviews, see Refs. 33 and 35

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Section: Discussionmentioning

confidence: 99%

Platelet-activating factor induces cardioprotection in isolated rat heart akin to ischemic preconditioning: role of phosphoinositide 3-kinase and protein kinase C activation

Penna

Alloatti

Cappello³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…Moreover, both acyl-linked and alkyl-linked acetylated phospholipids have been identified in stimulated human keratinocytes in culture (Travers et al, 1996(Travers et al, , 1997 (1) PAF has direct and potent effects upon cardiac function and has been implicated in cardiovascular (patho)physiology (Evangelou, 1994;Prescott et al, 1996Prescott et al, ,1997Feuerstein et al, 1997;Yamada et al, 1998); (2)PAF-like phospholipids (oxidized-PC) and PAF-AH may be involved in the pathogenesis of atherosclerosis (see above); (3)salivary PAF levels are significantly increased in subjects with periodontal disease (Fig. 5); (4)salivary PAF levels are transiently increased in subjects presenting with myocardial infarction (Jones et al, 1994); and (5)periodontitis appears to be a risk factor for cardiovascular disease (including accelerated or severe atherosclerosis, myocardial infarction, and stroke) (Beck et al, 1996(Beck et al, , 1998.…”

Section: (E) Paf In Bone Biologymentioning

confidence: 99%

“…Moreover, we now know that these unique phospholipids may participate in diverse (patho)physiologic events, including cell-cell adhesive interactions, intra-and intercellular signal transduction, cell differentiation, apoptosis, angiogenesis, neurotransmission, reproductive biology, cardiovascular homeostasis, ocular physiology, allergy, gastrointestinal, renal, or pulmonary tissue injury, organ transplantation rejection, and septic shock or systemic inflammatory response syndrome (cf. Zimmerman et al, 1993Zimmerman et al, , 1997Tokumura, 1995;Izzo, 1996;Maclennan et al, 1996;Bazan et al, 1997;Feuerstein et al, 1997;Muzya, 1997, 1998;Mathiak et al, 1997;Muguruma et al, 1997;Prescott, 1997;Tetta et al, 1997;Fink, 1998;Bazan, 1998 chronic inflammation. These inflammatory cells include the PMN, monocyte/macrophage, vascular endothelial cell, lymphocyte, mast cell, basophil, eosinophil, and platelet.…”

Section: (I) Introductionmentioning

confidence: 99%

“…Details regarding much of this PAF pathobiology are provided in a series of relatively recent reviews (cf. Zimmerman et al, 1993Zimmerman et al, , 1997Tokumura, 1995;Izo, 1996;Maclennan et al, 1996;Bazan et at., 1997;Feuerstein et al, 1997;Muzya, 1997, 1998;Mathiak et at, 1997;Muguruma et at., 1997;Prescott, 1997;Tetta et at., 1997;Fink, 1998;Kulikov and Muzya, 1998). The following will briefly focus upon the pro-inflammatory properties of PAY.…”

Section: (I) Introductionmentioning

confidence: 99%

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PAF, a Putative Mediator of Oral Inflammation

McManus

Pinckard

2000

Critical Reviews in Oral Biology & Medicine

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PAF, or platelet-activating factor, is a family of structurally related phospholipids (1 -O-alkyl/acyl/alkenyl-2-acetylsn-glycero-3-phosphocholine) which possesses a wide spectrum of potent pro-inflammatory actions. These phospholipids are synthesized by a diverse array of cells, including neutrophilic polymorphonuclear leukocytes (PMN), platelets, mast cells, monocytes/macrophages, vascular endothelial cells, and lymphocytes. PAF targets these and other cells via specific, G-proteincoupled receptors to initiate intracrine, autocrine, paracrine, and juxtacrine cell activation. Of importance, these unique acetylated phospholipids are frequently synthesized in concert with pro-inflammatory lipid mediators derived from arachidonic acid. Since PAF synergizes with these and other mediators to amplify the inflammatory response, it seems likely that PAF plays an integral, perhaps pivotal, role in acute and chronic inflammatory processes. PAF is present in the mixed saliva of dentate, but not edentulous, human subjects. The levels of PAF in mixed saliva or in gingival crevicular fluid and tissues are significantly increased during oral inflammatory conditions such as periodontitis and mucositis. Interestingly, the levels of salivary PAF correlate with the extent/severity of these oral diseases. These observations suggest that PAF may participate in pathophysiologic events during the course of oral inflammation. The availability of specific PAF receptor antagonists and human recombinant PAF-acetylhydrolase (PAF-AH), a plasma enzyme which rapidly destroys PAF, should provide clinical tools for the investigation of the role of PAF in these and other inflammatory disorders; and perhaps, ultimately, some of these reagents may prove to be therapeutically useful in the treatment and management of these conditions.

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“…PAF is also involved in several pathophysiology of various orIgInal artIcle Platelet-activating factor (PAF) receptor binding activity of the roots of Enicosanthellum pulchrum inflammatory diseases, including asthma, systemic lupus erythematosus, rheumatoid arthritis and Crohn's disease (Imarzumi et al, 1995;Zimmerman et al, 2002). The development of potent and selective PAF receptor antago nists has been particularly valuable for studies on the pathophysiology of PAF (Feuerstein et al, 1997). A number of natural PAF antagonists have been identified including ginkgolides from Ginkgo biloba L. (Ginkgoaceae) (Braquet et al, 1985), kadsurenone from Piper futokadsurae Sieb.…”

Section: Introductionmentioning

confidence: 99%

Platelet-activating factor (PAF) receptor binding activity of the roots ofEnicosanthellum pulchrum

Nordin

Jalil

Jantan

et al. 2011

Pharmaceutical Biology

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Platelet-activating factor and cardiac diseases: therapeutic potential for PAF inhibitors

Cited by 29 publications

References 121 publications

Platelet-activating factor induces cardioprotection in isolated rat heart akin to ischemic preconditioning: role of phosphoinositide 3-kinase and protein kinase C activation

Platelet-activating factor induces cardioprotection in isolated rat heart akin to ischemic preconditioning: role of phosphoinositide 3-kinase and protein kinase C activation

PAF, a Putative Mediator of Oral Inflammation

Platelet-activating factor (PAF) receptor binding activity of the roots ofEnicosanthellum pulchrum

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