Cardiovascular research
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Cardiovascular research · May 2008
Activation of fractalkine/CX3CR1 by vascular endothelial cells induces angiogenesis through VEGF-A/KDR and reverses hindlimb ischaemia.
The present study investigated the detailed mechanism by which fractalkine (Fkn), a CX3C chemokine, induces angiogenesis and its functional implication in alleviating ischaemia in vivo. ⋯ Fkn-induced activation of CX3CR1 by ECs leads to in vivo angiogenesis through two sequential steps: the induction of HIF-1alpha and VEGF-A gene expression by CX3CR1 activation and the subsequent VEGF-A/KDR-induced angiogenesis. The potent induction of angiogenesis by Fkn can be used as a therapeutic strategy for alleviating peripheral ischaemia.
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Cardiovascular research · Apr 2008
Adiponectin protects against myocardial ischaemia-reperfusion injury via AMP-activated protein kinase, Akt, and nitric oxide.
Cardiovascular disease and type 2 diabetes mellitus are associated with low plasma concentration of adiponectin. The aim of this study was to investigate whether adiponectin exerts cardioprotective effects during myocardial ischaemia-reperfusion and whether this effect is related to the production of nitric oxide (NO). ⋯ Adiponectin protects from myocardial contractile dysfunction and limits infarct size following ischaemia and reperfusion by a mechanism involving activation of AMPK and production of NO.
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Cardiovascular research · Apr 2008
Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of toll-like receptor 9.
Myocardial function is severely compromised during sepsis. Several underlying mechanisms have been proposed. The innate immune system, i.e. toll-like receptor (TLR) 2 and 4, significantly contributes to cardiac dysfunction. Little is known regarding TLR9 and its pathogenic ligand bacterial DNA in the myocardium. We therefore studied the role of TLR9 in myocardial inflammation and cardiac contractility. ⋯ Our data suggest that bacterial DNA contributes to myocardial cytokine production and loss of cardiomyocyte contractility via TLR9.
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Cardiovascular research · Apr 2008
Disruption of phospholipase Cgamma1 signalling attenuates cardiac tumor necrosis factor-alpha expression and improves myocardial function during endotoxemia.
Lipopolysaccharide (LPS) induces tumor necrosis factor-alpha (TNF-alpha) expression in cardiomyocytes, which contributes to myocardial dysfunction during sepsis. The purpose of this study was to investigate the role of phosphatidylinositol (PI) phospholipase Cgamma1 (PLCgamma1) in cardiac TNF-alpha expression, and myocardial dysfunction during endotoxemia. ⋯ PLCgamma1 signalling induces cardiac TNF-alpha expression and myocardial dysfunction during LPS stimulation. The action of PLCgamma1 on TNF-alpha expression is mediated through IP3/IP3R pathways. The present results suggest that PLCgamma1 may be a potential therapeutic target for myocardial dysfunction in sepsis.
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Cardiovascular research · Jan 2008
Infarct size limitation by adrenomedullin: protein kinase A but not PI3-kinase is linked to mitochondrial KCa channels.
Adrenomedullin (ADM) has been shown to protect the heart against ischaemic injury, but little is known of the underlying mechanism. Mitochondrial Ca(2+)-activated K(+) (mitoK(Ca)) channels play a key role in cardioprotection. This study examined whether mitoK(Ca) channel is involved in the protection afforded by ADM. ⋯ ADM augments the opening of mitoK(Ca) channels by PKA activation, but not by PI3-K activation. ADM treatment prior to ischaemia reduces infarct size via PKA-mediated activation of mitoK(Ca) channels. On the other hand, ADM treatment upon reperfusion reduces infarct size via a PI3-K-mediated pathway without activating mitoK(Ca) channels.