Cardioprotection From Ischemia/Reperfusion Injury

Minamino, Tetsuo

doi:10.1253/circj.cj-12-0132

Cited by 105 publications

(82 citation statements)

References 99 publications

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“…1, 21 Although reperfusion can salvage myocardium after sustained ischemia, the reperfusion itself paradoxically induces myocardial injury, named "reperfusion injury", which attenuates the benefits of myocardial reperfusion. 22 Among the different strategies to limit the no reflow phenomenon, that of reducing distal embolization with a manual thrombus aspiration device is promising. 23 Despite the logical advantage of thrombus aspiration during PCI, however, a previous early study failed to confirm superiority of this approach in reducing infarct size or death rates.…”

Section: Discussionmentioning

confidence: 99%

Vaporizing Thrombus With Excimer Laser Before Coronary Stenting Improves Myocardial Reperfusion in Acute Coronary Syndrome

Shishikura

Otsuji

Takiuchi

et al. 2013

Circ J

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Section: Discussionmentioning

confidence: 99%

Vaporizing Thrombus With Excimer Laser Before Coronary Stenting Improves Myocardial Reperfusion in Acute Coronary Syndrome

Shishikura

Otsuji

Takiuchi

et al. 2013

Circ J

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“…Ischemia/reperfusion (I/R) cardiovascular damage is a serious problem worldwide [1]. I/R defects are characterized by cardiomyocyte death and metabolism imbalance [2].…”

Section: Introductionmentioning

confidence: 99%

Real-Time Detection of Cardiomyocyte Phenomena under Hypoxia via Cell Analysis iCELLigence System

Ho¹,

Kuo²

2017

J Tradi Med Clin Natur

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Ischemia/reperfusion (I/R) injury of cardiomyocytes is a leading cause of morbidity and mortality. Moreover, I/R injury induce overproduction of reactive oxygen species and causes cardiomyocyte death under hypoxia conditions. However, methods for monitoring cell conditions in real-time under hypoxia conditions are limited. In this study, we used a novel analysis tool, the iCELLigence System, to analyze the effect of hypoxia on H9c2 cells. The results showed that hypoxia caused cell growth inhibition or death via overproduction of reactive oxygen species.

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“…Although all four AR subtypes are expressed in the mammalian heart (11,12), the well-known protective effects of adenosine in this tissue are predominantly mediated by the adenosine A 1 receptor (A 1 AR) subtype, especially under conditions of ischemia and reperfusion injury (13)(14)(15)(16)(17). Unfortunately, the transition of A 1 AR agonists into the clinic has been severely hindered because of high doses causing on-target bradycardia, atrioventricular block, and hypotension (13,18).…”

mentioning

confidence: 99%

Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist

Valant

May

Aurelio

et al. 2014

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

145

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The concepts of allosteric modulation and biased agonism are revolutionizing modern approaches to drug discovery, particularly in the field of G protein-coupled receptors (GPCRs). Both phenomena exploit topographically distinct binding sites to promote unique GPCR conformations that can lead to different patterns of cellular responsiveness. The adenosine A 1 GPCR (A 1 AR) is a major therapeutic target for cardioprotection, but current agents acting on the receptor are clinically limited for this indication because of ontarget bradycardia as a serious adverse effect. In the current study, we have rationally designed a novel A 1 AR ligand (VCP746)-a hybrid molecule comprising adenosine linked to a positive allosteric modulator-specifically to engender biased signaling at the A 1 AR. We validate that the interaction of VCP746 with the A 1 AR is consistent with a bitopic mode of receptor engagement (i.e., concomitant association with orthosteric and allosteric sites) and that the compound displays biased agonism relative to prototypical A 1 AR ligands. Importantly, we also show that the unique pharmacology of VCP746 is (patho)physiologically relevant, because the compound protects against ischemic insult in native A 1 AR-expressing cardiomyoblasts and cardiomyocytes but does not affect rat atrial heart rate. Thus, this study provides proof of concept that bitopic ligands can be designed as biased agonists to promote on-target efficacy without on-target side effects.

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Cardioprotection From Ischemia/Reperfusion Injury

Cited by 105 publications

References 99 publications

Vaporizing Thrombus With Excimer Laser Before Coronary Stenting Improves Myocardial Reperfusion in Acute Coronary Syndrome

Vaporizing Thrombus With Excimer Laser Before Coronary Stenting Improves Myocardial Reperfusion in Acute Coronary Syndrome

Real-Time Detection of Cardiomyocyte Phenomena under Hypoxia via Cell Analysis iCELLigence System

Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist

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