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Biomedical subjects

Shinji Negoro

Publications and source records attributed to Shinji Negoro.

10 recordsLinked to original sources
PubMed2005

STAT3 mediates cardioprotection against ischemia/reperfusion injury through metallothionein induction in the heart.

OBJECTIVE: Activation of signal transducer and activator of transcription 3 (STAT3) was reported to be correlated with myocardial protection against ischemia/reperfusion (I/R) injury in ischemic preconditioning. Here, we tested the causality between STAT3 activity and cardioprotection. We also addressed the molecular mechanism for its cardioprotection. METHODS AND RESULTS: Cardiac-specific transgenic mice expressing constitutively active STAT3 (TG) were generated and exposed to I/R injury. TG hearts exhibited infarcts that reduced by 60.3% in size, compared with nontransgenic littermates (NTG). By measuring dichlorofluorescein (DCF) and 8-isoprostane, reactive-oxygen-species (ROS)-induced metabolites, it was revealed that ROS were generated to lesser extent in TG hearts than in NTG in response to I/R stress. In parallel, ROS scavengers, metallothionein1 (MT1), and metallothionein2 (MT2) were markedly up-regulated in TG hearts. Finally, homozygous deletion of the MT1 and MT2 genes abrogated cardioprotective effect of STAT3 against I/R injury with the cancellation of its ROS-scavenging effects. CONCLUSIONS: Activation of STAT3 protects myocardium from I/R injury in vivo. STAT3 mediates cardioprotection at least partially through MT1 and 2. STAT3 is a potential therapeutic target for I/R injury.

Animals↗
PubMed2003

Evaluation of the PercuSurge Guardwire Plus Temporary Occlusion and Aspiration System during primary angioplasty in acute myocardial infarction.

Thirty patients with acute myocardial infarction (AMI) underwent primary angioplasty under distal protection of PercuSurge GuardWire Plus Temporary Occlusion and Aspiration System. Before angioplasty, protection of the distal circulation was achieved with the system, followed by balloon angioplasty and/or stenting and debris aspiration. Technical device success was 100%. Distal occlusion was well tolerated in all patients. Mean total distal occlusion time was 7.3 +/- 5.4 min. Macroscopically visible debris was aspirated from 29 cases (96.7%). Postprocedural Thrombolysis in Myocardial Infarction flow grade 3 was achieved in all cases (100%, vs. 16.7% at baseline). Myocardial blush flow grade 3 was achieved in 26 cases (86.7%). Regression of ST segment elevation >/= 50% was shown in 23 cases (76.7%). No patient developed angiographic evidence of no-reflow or distal embolization. Both angiographic and procedural success were 100%. The system is feasible, safe, and effective for distal protection against embolism during primary angioplasty in AMI.

Aged↗
PubMed2002

Aldosterone augments endothelin-1-induced cardiac myocyte hypertrophy with the reinforcement of the JNK pathway.

Aldosterone is thought to regulate cardiac work independently of sodium retention, though the mechanisms remain to be known. In the present study, we have demonstrated that aldosterone reinforces endothelin-mediated cardiac hypertrophy with the increase in cell surface area and upregulation of the transcripts characteristic of hypertrophy. We have also shown that aldosterone augments c-Jun N-terminal kinase activation induced by endothelin-1. Taken together, it is suggested that aldosterone modulates cardiac hypertrophy, at least partially, synergistically with extracellular signals that have been shown to be involved in cardiac remodeling.

Aldosterone↗
PubMed2002

Bcl-xl reduces doxorubicin-induced myocardial damage but fails to control cardiac gene downregulation.

OBJECTIVE: We recently reported that doxorubicin (Dox), an effective anti-cancer drug, induces apoptosis in cardiac myocytes in association with reduction of Bcl-xl expression. In the present study, we further examined whether overexpression of Bcl-xl ameliorates Dox-induced cardiac myocyte damage. METHODS AND RESULTS: Overexpression of the Bcl-xl gene by adenovirus vector resulted in an 11-fold increase in Bcl-xl protein in neonatal rat cardiac myocytes (BCL) compared to that in cells with beta-galactosidase gene transfection (CTL). Although Dox treatment generated similar amounts of reactive oxygen species (ROS) in BCL and CTL, cell viability was maintained and the number of apoptotic cardiac myocytes was significantly decreased in BCL. Cytochrome c release and enhanced caspase-3 activity after Dox treatment were significantly suppressed and Bax expression level was decreased in BCL. Cardiac-specific gene expression is known to be inhibited by Dox. The expression of cardiac alpha-actin and sarcoplasmic reticulum Ca(2+)-ATPase 2a mRNA was equally inhibited in BCL and CTL after Dox treatment. CONCLUSIONS: Overexpression of Bcl-xl in cardiac myocytes failed to regulate Dox-induced ROS generation and cardiac-specific gene downregulation but inhibited apoptosis accompanied by reduction of Bax protein.

Adenoviridae↗
PubMed2001

Cardiac-specific activation of signal transducer and activator of transcription 3 promotes vascular formation in the heart.

Signal transducer and activator of transcription 3 (STAT3) functions in cell proliferation, differentiation, and cell survival. Previously, we have demonstrated that the activation of STAT3 is required for glycoprotein 130-mediated induction of VEGF in cardiac myocytes, but the functional importance of STAT3 as an angiogenic mediator remains to be determined. To address this issue, we first generated the adenoviral vector expressing constitutively active STAT3 (caSTAT3). Adenoviral gene transfer of caSTAT3 induced an increase in the expression of VEGF in cultured cardiomyocytes. The conditioned medium from caSTAT3-transfected cardiomyocyte culture promoted endothelial tubule formation, which was inhibited by anti-VEGF antibody. Next, we generated the transgenic (TG) mice with cardiac-specific overexpression of caSTAT3 and demonstrated that caSTAT3 TG mice showed evidence of VEGF induction in the hearts. The caSTAT3 TG hearts also demonstrated increased capillary density accompanied by an increase in the expression of VE-cadherin, an endothelial-specific component. These data indicate that caSTAT3 TG hearts exhibit an enriched vascular structure compared with non-transgenic hearts. The study presented here provides the first evidence that activation of STAT3 controls vessel growth in vivo and suggests that STAT3 contributes to cardiac adaptation by regulating vascular function under the conditions of stress.

Acute-Phase Proteins↗