Role of β1- and β2-Adrenoceptor Subtypes in Preconditioning Against Myocardial Dysfunction after Ischemia and Reperfusion

Frances, Carole; Nazeyrollas, Pierre; Prévost, Alain; Moreau, F.; Pisani, Jean; Davani, Siamak; Kantelip, Jean-Pierre; Millart, Hervé

doi:10.1097/00005344-200303000-00008

Cited by 48 publications

(46 citation statements)

References 40 publications

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“…It has been reported that brief exposure to b-adrenergic receptor agonist isoproterenol prior to ischaemia is protective against ischaemic injury in rat and murine hearts. 33,34 Furthermore, activation of cAMP/PKA is required for ischaemic preconditioning, 35,36 in which lethal injury to the heart can be dramatically blunted by brief conditioning periods of ischaemia. 37 Recent study by Cao et al 38 demonstrated that in rat hearts cardioprotection conferred by ischaemic preconditioning was abolished by paxilline administered before ischaemia.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Infarct size limitation by adrenomedullin: Protein kinase A but not PI3-kinase is linked to mitochondrial KCa channels

Nishida¹,

Sato²,

Miyazaki³

et al. 2007

Cardiovascular Research

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Infarct size limitation by adrenomedullin: Protein kinase A but not PI3-kinase is linked to mitochondrial KCa channels

Nishida¹,

Sato²,

Miyazaki³

et al. 2007

Cardiovascular Research

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“…Blocking PKC prevents preconditioning (7,19,26,29). Recent studies have also implicated the ␤ 1 -AR, PKA, cAMP pathway in preconditioning (15,27,43,44). Asimakis and coworkers (3,4) found that brief ␤-adrenergic stimulation preconditions the rat heart against postischemic contractile dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, PKA that is activated by the ␤ 2 -receptor is compartmentalized to a subsarcolemmal space and is not involved in mitochondrial phosphorylation (22). Also, it was shown in norepinephrinedepleted rat hearts that perfusion for 5 min with isoproterenol before ischemia-reperfusion provided protection against myocardial damage similar to that of ischemic preconditioning; this protection was prevented by ␤ 1 -AR blockade but not by ␤ 2 -AR blockade (15). Together these data suggest that activation of the ␤ 1 -AR by ischemia may be the triggering mechanism for ischemic preconditioning mediated by PKA as well as the mechanism by which CcO function is altered during ischemia.…”

mentioning

confidence: 99%

β₁-Adrenoreceptor activation contributes to ischemia-reperfusion damage as well as playing a role in ischemic preconditioning

Spear¹,

Prabu²,

Galati³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Protein kinase A (PKA) activation has been implicated in early-phase ischemic preconditioning. We recently found that during ischemia PKA activation causes inactivation of cytochrome- c oxidase (CcO) and contributes to myocardial damage due to ischemia-reperfusion. It may be that β-adrenergic stimulation during ischemia via endogenous catecholamine release activates PKA. Thus β-adrenergic stimulation may mediate both myocardial protection and damage during ischemia. The present studies were designed to determine the role of the β1-adrenergic receptor (β1-AR) in myocardial ischemic damage and ischemic preconditioning. Langendorff-perfused rabbit hearts underwent 30-min ischemia by anterior coronary artery ligation followed by 2-h reperfusion. Occlusion-reperfusion damage was evaluated by delineating the nonperfused volume of myocardium at risk and volume of myocardial necrosis after 2-h reperfusion. In some hearts ischemic preconditioning was accomplished by two 5-min episodes of global low-flow ischemia separated by 10 min before coronary occlusion-reperfusion. Orthogonal electrocardiograms were recorded, and coronary flow was monitored by a drip count. Three hearts from each experimental group were used to determine mitochondrial CcO and aconitase activities. Two-hour reperfusion after occlusion caused an additional decrease in CcO activity vs. that after 30-min occlusion alone. Blocking the β1-AR during occlusion-reperfusion reversed CcO activity depression and preserved myocardium at risk for necrosis. Similarly, mitochondrial aconitase activity exhibited a parallel response after occlusion-reperfusion as well as for the other interventions. Furthermore, classic ischemic preconditioning had no effect on CcO depression. However, blocking the β1-AR during preconditioning eliminated the cardioprotection. If the β1-AR was blocked after preconditioning, the myocardium was preserved. Interestingly, in both of the latter cases the depression in CcO activity was reversed. Thus the β1-AR plays a dual role in myocardial ischemic damage. Our findings may lead to therapeutic strategies for preserving myocardium at risk for infarction, especially in coronary reperfusion intervention.

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“…cMyBP-C AllPϩ:(t/t) hearts were subjected to left ventricular cardiac ischemia for 1 h followed by 24 h of reperfusion to induce myocardial infarction and cell death. The ␤-adrenergic agonist isoproterenol was used as a positive control to protect the heart against ischemic injury (18). Remarkably, cMyBP-C AllPϩ:(t/t) mice showed a greater reduction (18 Ϯ 2%) in infarcted area normalized to area at risk (AAR) (AAR was not different between the groups), compared with the cMyBP-C WT:(t/t) (35 Ϯ 2%) and NTG (37 Ϯ 2%) controls (Fig.…”

mentioning

confidence: 99%

Cardiac myosin binding protein c phosphorylation is cardioprotective

Sadayappan

Osińska

Klevitsky

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

191

294

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Cardiac myosin binding protein C (cMyBP-C) has three phosphorylatable serines at its N terminus (Ser-273, Ser-282, and Ser-302), and the residues' phosphorylation states may alter thick filament structure and function. To examine the effects of cMyBP-C phosphorylation, we generated transgenic mice with cardiac-specific expression of a cMyBP-C in which the three phosphorylation sites were mutated to aspartic acid, mimicking constitutive phosphorylation (cMyBP-C AllP؉ ). The allele was bred into a cMyBP-C null background (cMyBP-C (t/t) ) to ensure the absence of endogenous dephosphorylated cMyBP-C. cMyBP-C AllP؉ was incorporated normally into the cardiac sarcomere and restored normal cardiac function in the null background. However, subtle changes in sarcomere ultrastructure, characterized by increased distances between the thick filaments, indicated that phosphomimetic cMyBP-C affects thick-thin filament relationships, and yeast two-hybrid data and pull-down studies both showed that charged residues in these positions effectively prevented interaction with the myosin heavy chain. Confirming the physiological relevance of these data, the cMyBP-C AllP؉:(t/t) hearts were resistant to ischemia-reperfusion injury. These data demonstrate that cMyBP-C phosphorylation functions in maintaining thick filament spacing and structure and can help protect the myocardium from ischemic injury.heart ͉ ischemia C ardiac myosin binding protein C (cMyBP-C) is localized to the sarcomere's thick filaments where it has structural and regulatory functions. MYBPC3 mutations account for 20-30% of all mutations linked to familial hypertrophic cardiomyopathy (1). cMyBP-C belongs to the intracellular Ig superfamily and is composed of Ig and fibronectin type-3 repeating domains (Fig. 1A). It is present not only in cardiac muscle, but also in skeletal muscle before the skeletal muscle-type isoforms are expressed, suggesting that the cardiac isoform is functional in early myofibrillogenesis and regenerating muscle (2, 3). cMyBP-C may modulate myosin assembly (4) and stabilize thick filaments (5). It binds titin via domains C8-C10 (6) and actin in the Pro-Alarich sequences between the C0 and C1 domains (7), which appear to be important for the precise arrangement of the actin-myosin filaments. Compared with the two skeletal muscle isoforms, the cardiac isoform contains an extra Ig domain at the N terminus (C0), an insertion of 28 residues within the C5 domain, and three potential phosphorylation sites that are substrates for cAMP-dependent PKA, Ca 2ϩ -calmodulin-activated kinase, and PKC (8). This region is located between the C1 and C2 domains of the N terminus, which binds to the subfragment 2 (S2) segment of myosin close to the lever arm domain (9-11), and this interaction may be dynamically regulated by the differential phosphorylation of cMyBP-C (12). cMyBP-C is the only thick filament protein that is differentially phosphorylated at multiple sites by the enzymes PKA, PKC, and Ca 2ϩ -calmodulin-activated kinase (13). Reconstitution studie...

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Role of β1- and β2-Adrenoceptor Subtypes in Preconditioning Against Myocardial Dysfunction after Ischemia and Reperfusion

Cited by 48 publications

References 40 publications

WITHDRAWN: Infarct size limitation by adrenomedullin: Protein kinase A but not PI3-kinase is linked to mitochondrial KCa channels

WITHDRAWN: Infarct size limitation by adrenomedullin: Protein kinase A but not PI3-kinase is linked to mitochondrial KCa channels

β₁-Adrenoreceptor activation contributes to ischemia-reperfusion damage as well as playing a role in ischemic preconditioning

Cardiac myosin binding protein c phosphorylation is cardioprotective

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Role of β1- and β2-Adrenoceptor Subtypes in Preconditioning Against Myocardial Dysfunction after Ischemia and Reperfusion

Cited by 48 publications

References 40 publications

WITHDRAWN: Infarct size limitation by adrenomedullin: Protein kinase A but not PI3-kinase is linked to mitochondrial KCa channels

WITHDRAWN: Infarct size limitation by adrenomedullin: Protein kinase A but not PI3-kinase is linked to mitochondrial KCa channels

β1-Adrenoreceptor activation contributes to ischemia-reperfusion damage as well as playing a role in ischemic preconditioning

Cardiac myosin binding protein c phosphorylation is cardioprotective

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β₁-Adrenoreceptor activation contributes to ischemia-reperfusion damage as well as playing a role in ischemic preconditioning