Cardioprotective Effect of Angiotensin-Converting Enzyme Inhibition Against Hypoxia/Reoxygenation Injury in Cultured Rat Cardiac Myocytes

Matoba, Satoaki; Tatsumi, Tomohide; Keira, Natsuya; Kawahara, Akira; Akashi, Kazuko; Kobara, Miyuki; Asayama, Jun; Nakagawa, Masao

doi:10.1161/01.cir.99.6.817

Cited by 79 publications

(58 citation statements)

References 29 publications

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“…Primary cultures of neonatal rat cardiac myocytes were prepared as described previously [21]. Cells were divided into 4 groups: a Control group in normal medium, a DOX group in medium with 1 μM DOX, a Cur group in medium with 5 μM Cur, and a DOX+Cur group in medium with 1 μM DOX and 5 μM Cur.…”

Section: Cardiomyocyte Isolations and Experimental Treatmentmentioning

confidence: 99%

Curcumin Attenuates Doxorubicin-Induced Cardiotoxicity by Inducing Autophagy via the Regulation of JNK Phosphorylation

Katamura¹,

Iwai-Kanai²,

Nakaoka³

et al. 2014

J Clin Exp Cardiolog

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Background and Objective: Doxorubicin (DOX) has been used in cancer therapy for several decades. However, cardiac complications induced by DOX dose-dependently limit the clinical implication at optimal antitumor efficacy. Curcumin (Cur), a natural compound, has been effective as an anticancer agent in various types of cancers. It also protects against cardiac hypertrophy and heart failure, though its effect on cardiomyopathy caused by DOX treatment is unclear. To elucidate the role of curcumin on heart failure, we used the DOX induced cardiomyopathy model and primary cultured cardiac myocytes. Method and Results:Male C57/BL6 mice were randomized to 4 courses of treatment administered for 4 weeks: Phosphate-Buffered Saline (PBS), Cur, DOX, and DOX+Cur. DOX-treated mice exhibited severe cardiac dysfunction, and the mortality was higher than that in PBS-treated mice. In DOX-treated mice, the number of apoptotic cardiac myocytes was higher and the fibrotic areas were larger than in PBS-treated mice. The cardiotoxic effects of DOX were ameliorated by treatment with Cur. In DOX-treated GFP-LC3 transgenic mice, Cur induced autophagy and decreased apoptosis in the heart. Cur also induced autophagy and suppressed DOX-induced apoptosis in neonatal rat cardiac myocytes. Inhibition of autophagy by 3-methyladenine decreased the cardioprotective effect of Cur. Furthermore, Cur decreased c-Jun N-terminal kinase (JNK) phosphorylation, resulting in reduction of apoptosis. The JNK inhibitor SP600125 abolished these effects. Conclusion:Cur protects the heart from DOX-induced cardiotoxicity by inducing autophagy and decreasing cardiomyocyte apoptosis. The mechanism involves JNK-mediated modification of apoptosis. Induction of cardiac autophagy may be a novel therapeutic approach for preventing DOX-induced cardiotoxicity.

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Section: Cardiomyocyte Isolations and Experimental Treatmentmentioning

confidence: 99%

Curcumin Attenuates Doxorubicin-Induced Cardiotoxicity by Inducing Autophagy via the Regulation of JNK Phosphorylation

Katamura¹,

Iwai-Kanai²,

Nakaoka³

et al. 2014

J Clin Exp Cardiolog

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“…Importantly, we did not observe any effect of ACE-AS on ACE mRNA, yet there was a marked decrease in the ACE protein expression, which indicates that the mechanism by which ACE-AS reduces ACE protein involves the post-transcriptional process. 20 A number of experimental and clinical studies show that ACE inhibitors are beneficial in treating acute myocardial infarction, and the benefits include preservation of left ventricular function 12,16 and myocardial cell integGene Therapy rity, 13,36 and reduction in reperfusion arrhythmias 15,16,37 and remodeling of myocardium. 36,38 However, chemical ACE inhibitors have several disadvantages, which include unpleasant side-effects 39 and need for frequent intake.…”

Section: Discussionmentioning

confidence: 99%

“…Others and ourselves have used this model extensively to study regulation of a variety of receptors and modulation of cardiac function by different agents. 13,25,26 In the isolated beating heart, cardiac function can be assessed independently of the influence of circulating blood cells and hormones, which may be considered an important advantage of this model. MDA, a lipid peroxidation product, and LDH, an enzyme in the cellular plasma, have also been previously used as indexes of tissue injury after ischemia/reperfusion.…”

Section: Discussionmentioning

confidence: 99%

“…4,[9][10][11] A large body of data indicates that ACE inhibitors protect myocardium against ischemia/reperfusion in in vitro and in vivo animal models. [2][3][4][12][13][14] Several clinical trials have ted with evidence of lipid peroxidation and enzyme leakage (MDA and LDH levels in the myocardium) and up-regulation of ACE protein expression. Administration of AS-ODN or captopril, but not IN-ODN, reduced Ang-II levels in the plasma, decreased ischemia/reperfusion-mediated cardiac functional deterioration and lipid peroxidation, and preserved LDH in the myocardium (all P Ͻ 0.05 versus the saline group).…”

Section: Introductionmentioning

confidence: 99%

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Protection against ischemia/reperfusion injury and myocardial dysfunction by antisense-oligodeoxynucleotide directed at angiotensin-converting enzyme mRNA

Chen

Mohuczy

et al. 2001

Gene Ther

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Angiotensin-converting enzyme (ACE) activity in the myocardium and angiotensin-II (Ang-II) levels in plasma increase after myocardial ischemia, which lead to exacerbation of myocardial injury and cardiac dysfunction. We examined the protective role of novel antisense-oligodeoxynucleotide (AS-ODN) directed at ACE mRNA in myocardial ischemic injury. Sprague-Dawley rats were treated with ACE-AS-ODN (200 g per rat, n = 8, i.v.) or inverted-ODN (IN-ODN, 200 g per rat, n = 8, i.v.), given with 600 g per rat of liposome DOTAP/DOPE. Hearts from AS-ODN-or IN-ODNtreated rats were excised, perfused in vitro, and subjected to 25 min of global ischemia followed by 30 min of reperfusion. Parallel groups of rats were given ACE inhibitor captopril (5 mg/kg, n = 8) or saline (n = 8) before excising the hearts. Ischemia/reperfusion resulted in myocardial dysfunction (increase in coronary perfusion pressure and LV end-diastolic pressure and a decrease in developed LV pressure) in the saline-treated rats. Myocardial dysfunction was associa-

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“…Particularly in several studies, hypoxia is the direct trigger and well-known stimulus of apoptosis independent of the neuronhumoral factors in various physiologic and pathologic conditions. 8) Some studies have indicated that ANP and CNP inhibit vascular smooth muscle growth [9][10][11] and ANP induces apoptosis in cultured vascular smooth muscle cells, 12) which infer the negative effect of natriuretic peptides on the cardiovascular system. In this regard, the role of BNP in mild hypoxia-induced cardiomyocytes apoptosis and the possible mechanism are of great interest to explore.…”

mentioning

confidence: 99%

B-Type Natriuretic Peptide Enhances Mild Hypoxia-Induced Apoptotic Cell Death in Cardiomyocytes

Wang

et al. 2007

Biological & Pharmaceutical Bulletin

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The natriuretic peptides are a family of small peptides that activates specific NP-bound guanylyl cyclase (GC) receptors and stimulates cGMP synthesis. Three main natriuretic peptides have been identified so far: atrial (ANP), B-type (BNP) and C-type natriuretic peptides (CNP). Among them, BNP having a common core structure of natriuretic peptides, which consists a 17-member disulfide ring with a highly conserved internal sequence of -FGXXXDRIGXXSGL-, plays an essential role in the maintenance of homeostasis such as natriuresis, diuresis, vasorelaxant effect and inhibits the activation of renin-angiotensin-aldosterone system under pathological conditions. 1) Expression of the three natriuretic peptide receptors (NPR-A, NPR-B, NPR-C) has been confirmed in human and rat cardiac tissue.2) Commonly, BNP exhibits its effects by preferentially binding to the NPR-A (also known as GC-A) which is coupled to cytoplasmic C-terminal GC catalytic domain and signals via formation of cGMP. 3,4) Although some studies have shown a compensatory role for BNP in heart disease, the precise contribution of BNP to the pathophysiology of heart is poorly understood.Ischemia is one of the most common pathological conditions in many cardiovascular diseases. Apoptotic cell death has been shown to be one of the major pathological events in a variety of cardiovascular ischemic conditions such as myocardial infarction.5) As the stimuli of cardiomyocyte apoptosis, a range of stress including mild hypoxic, 6) ischemic and neurohumoral stimulation 7) has been illustrated in vitro. Particularly in several studies, hypoxia is the direct trigger and well-known stimulus of apoptosis independent of the neuronhumoral factors in various physiologic and pathologic conditions.8) Some studies have indicated that ANP and CNP inhibit vascular smooth muscle growth [9][10][11] and ANP induces apoptosis in cultured vascular smooth muscle cells, 12) which infer the negative effect of natriuretic peptides on the cardiovascular system. In this regard, the role of BNP in mild hypoxia-induced cardiomyocytes apoptosis and the possible mechanism are of great interest to explore. The present study was therefore designed to examine whether BNP influenced apoptotic cardiomyocyte death under mild hypoxia which has been proved to trigger the intrinsic mitochondrial death signaling pathway, and whether cGMP was involved in the process. MATERIALS AND METHODSPrimary Culture of Cardiomyocytes Primary culture of neonatal rat cardiomyocytes were prepared as described before.13) In brief, the ventricles of 3-d-old Sprague-Dawley rats were digested with 0.08% trypsin and 0.06% collagenase II (Sigma Chemical Co., U.S.A.). The cells in suspension were collected, washed and seeded in 24 well plates at a density of 2ϫ10 5 cells. All cells were cultured in a medium containing 85% DMEM (Invitrogen, CA, U.S.A.) and 15% fetal bovine serum. The proportion of cardiomyocytes was enriched by the preplating method. BrdU (0.1 mM, Sigma, U.S.A.) was added within the first 48 h to inhibit fibrob...

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Cardioprotective Effect of Angiotensin-Converting Enzyme Inhibition Against Hypoxia/Reoxygenation Injury in Cultured Rat Cardiac Myocytes

Cited by 79 publications

References 29 publications

Curcumin Attenuates Doxorubicin-Induced Cardiotoxicity by Inducing Autophagy via the Regulation of JNK Phosphorylation

Curcumin Attenuates Doxorubicin-Induced Cardiotoxicity by Inducing Autophagy via the Regulation of JNK Phosphorylation

Protection against ischemia/reperfusion injury and myocardial dysfunction by antisense-oligodeoxynucleotide directed at angiotensin-converting enzyme mRNA

B-Type Natriuretic Peptide Enhances Mild Hypoxia-Induced Apoptotic Cell Death in Cardiomyocytes

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