Biomedical subjects

Masafumi Kitakaze

Publications and source records attributed to Masafumi Kitakaze.

130 records · Page 8Linked to original sources

PubMed2002

Adenosine-induced cardiac gene expression of ischemic murine hearts revealed by cDNA array hybridization.

Because many endogenous substances, including adenosine, contribute to the pathophysiology of ischemic hearts, the present study was designed to investigate the transcription responses of murine hearts to ischemia with or without administration of an inhibitor of adenosine receptor, 8-sulfophenyltheophylline (8SPT). Sixty minutes after ligation of the proximal site of the left coronary artery with (n=9) or without (n=9) 8SPT, the hearts were excised to obtain mRNA for cDNA array analysis. In 18,376 cDNA, 2 known genes were upregulated over 10-fold, and 11 known genes were upregulated 5.0-9.9-fold. 8SPT reduced the expressed gene to the control levels. Furthermore, 32 unknown genes were also upregulated over 5.0-fold. In contrast, 11 known genes were downregulated below 0.2-fold, and 64% of the downregulated genes were restored by 8SPT. The 7 unknown genes were downregulated to levels below 0.2-fold. Therefore, it was concluded that the cardiac expression of 24 known and 39 unknown genes was modulated by ischemic stress, and that these genes appeared to be related to the pathophysiology of the ischemic heart because endogenous adenosine modulated their expression.

Adenosine↗

PubMed2002

Cellular mechanisms for the treatment of chronic heart failure: the nitric oxide- and adenosine-dependent pathways.

Accumulated evidence suggests that several drugs proven to improve survival in patients with chronic heart failure (CHF) enhance endogenous nitric oxide (NO)- and/or adenosine-dependent pathways. Indeed, we and others have demonstrated that: i) antagonists of either renin-angiotensin-aldosterone or beta-adrenergic systems enhance NO-dependent pathways; ii) although carvedilol and amlodipine belong to different drug classes, both of them can increase cardiac adenosine levels; iii) increased adenosine levels by dipyridamole are associated with the improvement of CHF. Interestingly, both NO and adenosine have multifactorial beneficial actions in cardiovascular systems. First of all, both of them induce vasodilation and decrease myocardial hypercontractility, which may contribute to a reduction in the severity of myocardial ischaemia. Both adenosine and NO are also involved in cardioprotection attributable to acute and late phases of ischaemic preconditioning, respectively. Secondly, they can modulate the neurohormonal systems that contribute to the progression of CHF. Thus, we propose that enhancement of endogenous NO and/or adenosine as potential therapeutic targets in a new strategy for the treatment for CHF.

Journal Article↗

PubMed2002

[Amelioration of ischemia- and reperfusion-induced myocardial injury by the selective estrogen receptor modulator, raloxifene, in the canine heart].

BACKGROUND: 17 beta-estradiol reduces myocardial infarct size which is mediated by nitric oxide (NO) and the opening of Ca (2+)-activated K+ (KCa) channels. Raloxifene, a selective estrogen receptor modulator, demonstrates acute coronary artery vasorelaxing effects. Whether raloxifene reduces ischemia/reperfusion injury and what mechanisms are involved in the cardioprotective effects were investigated. METHODS: Infarct size was measured in open-chest dogs following occlusion of the left anterior descending coronary artery for 90 min and subsequent reperfusion for 6 hr. The incidence of ventricular fibrillations during reperfusion period was also observed. Infusion of raloxifene and/or other drugs into the left anterior descending coronary artery was initiated 10 min before coronary occlusion and continued until 1 hr after reperfusion started without an occlusion period. RESULTS: Infarct size was reduced in the raloxifene (5 micrograms/kg/min) group compared with the control group (6.8 +/- 4.2% vs 40.9 +/- 3.9% of the area at risk, p < 0.01). Either NG-nitro-L-arginine methyl ester, the inhibitor of NO synthase (infarct size: 22.8 +/- 5.4%, p < 0.05 vs raloxifene or the control) or charbdotoxin, the blocker of KCa channels (infarct size: 23.5 +/- 5.1%, p < 0.05 vs raloxifene or the control), partially attenuated the infarct size-limiting effect, and combination of both agents completely abolished the effect (infarct size: 37.7 +/- 5.8%). The incidence of ventricular fibrillations was also less in the raloxifene group than in the control group(11% vs 44%, p < 0.05). CONCLUSIONS: Raloxifene reduces myocardial infarct size and the incidence of ventricular fibrillations by NO- and the opening of KCa channels-dependent mechanisms in canine hearts.

Animals↗

PubMed2002

[The role of HB-EGF in angiotensin II--signaling].

G-protein coupled receptor agonists such as phenylephrine, angiotensin II, and endothelin-1 are well-known inducers of cardiac hypertrophy. We demonstrated that both metalloproteinase inhibitor and HB-EGF neutralizing antibody abrogated the trans-activation of the receptor for epidermal growth factor by phenylephrine, angiotensin II, or endothelin-1 in cultured rat neonatal cardiomyocytes. We cloned ADAM12(a disintegrin and metalloprotease 12) as a specific enzyme to cleave HB-EGF in cardiomyocytes. We also showed that a metalloproteinase inhibitor attenuates cardiac hypertrophy in aortic banding mice. These data suggest that release of HB-EGF by ADAM12 plays a crucial role in hypertrophic signaling of cardiomyocytes, and that inhibition of HB-EGF shedding could be a potent therapeutic strategy for cardiac hypertrophy.

Angiotensin II↗