Effect of ATP-Sensitive Potassium Channel Agonists on Ventricular Remodeling in Healed Rat Infarcts

Lee, Tsung-Ming; Lin, Mei-Shu; Chang, Nen-Chung

doi:10.1016/j.jacc.2007.11.067

Cited by 51 publications

(66 citation statements)

References 33 publications

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“…Work presented in this issue of J Mol Med may bring us a little closer to the mechanisms involved [6]. Lee et al present an evidence that membrane ERα attenuates myocardial fibrosis via Ras homolog member A (RhoA) and Rho-associated, coiled-coil containing protein kinase 1 (ROCK)-mediated actin remodeling [6,7].The authors ovariectomized (OVX) female Wistar rats. Two weeks later, the left-anterior descending coronary artery was ligated, a standard myocardial infarction model.…”

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confidence: 99%

ERα on the cell membrane helps the heart

Luft

2013

J Mol Med

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17β-Estradiol is a lipophilic steroid hormone that can pass through the cell's phospholipid membranes and bind to two different classes of estrogen receptors (ERs): the nuclear steroid hormone receptors ERα and ERβ [1] and the G proteincoupled receptor (GPER) also known as the G proteincoupled receptor 30 (GPR30) [2,3]. Hormone binding triggers distinct responses in different tissues through genomic, non-genomic, and combined pathways.The classical ERs are ligand-activated transcription factors. Hormone binding triggers their dimerization, migration to the nucleus, and binding to hormone-response elements on DNA. A separate gene, ESR1 and ESR2, encodes each receptor. ERα and ERβ exhibit significant overall sequence homology, and both are composed of five domains. Since ERα and ERß are co-expressed in many cell types, the receptors may form ERα (αα) or ERβ (ββ) homodimers or ERαβ (αβ) heterodimers. However, there is increasing evidence that ERs are also present on the endothelial cell surface where they can signal in a non-genomic fashion. ERs may associate with cell membranes by attachment to caveolin-1 and form complexes with G proteins, striatin, and receptor tyrosine kinases such as epidermal growth factor (EGFR), insulin-like growth factor (IGF-1), and non-receptor tyrosine kinases such as Src. By interacting with striatin, ERs may influence cytosolic Ca 2+ and nitric oxide. As mentioned, estrogen also binds to GPER resulting in intracellular calcium mobilization and synthesis of phosphatidylinositol (3,4,5)-triphosphate [3].Endogenous estrogens contribute to the low prevalence of atherosclerotic vascular disease in premenopausal women with intact ovarian function, and cessation of estrogen production following menopause increases cardiovascular risk [4]. Myocardial remodeling, defined as the molecular and cellular events after an injury to the myocardium such as myocardial infarction, is more favorable in women than in men, and estrogen is believed to be responsible [5]. Work presented in this issue of J Mol Med may bring us a little closer to the mechanisms involved [6]. Lee et al. present an evidence that membrane ERα attenuates myocardial fibrosis via Ras homolog member A (RhoA) and Rho-associated, coiled-coil containing protein kinase 1 (ROCK)-mediated actin remodeling [6,7].The authors ovariectomized (OVX) female Wistar rats. Two weeks later, the left-anterior descending coronary artery was ligated, a standard myocardial infarction model. The rats were then assigned to placebo or the implantation of a 60-day release pellet of 17β-estradiol. Four weeks were allowed to pass to permit remodeling to be completed in intact female rats that have endogenous estrogen, OVX rats that have no estrogen, or OVX rats receiving replacement 17β-estradiol. The collagen area fraction was twice as large in the estrogen-deficient OVX group than in the two groups with estrogen, a finding that was verified by measuring the proline content. RhoA was more phosphorylated in the OVX controls than in the two groups with estrogen...

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confidence: 99%

ERα on the cell membrane helps the heart

Luft

2013

J Mol Med

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“…The heart was perfused with a non-circulating modified Tyrode's solution containing (in mmol/L): glucose 5.5, NaCl 117.0, NaHCO3 23.0, KCl 4.6, NaH2PO4 0.8, MgCl2 1.0, and CaCl2 2.0, equilibrated at 37°C and oxygenated with a 95% O2 to 5% CO2 gas mixture. 27 The drugs were infused for 60 min. At the end of the study, all hearts (n=5 each group) were used for performing Western analysis for p-CREB (Ser-133) and NGF protein at the remote zone (>2 mm outside the infarct).…”

Section: Experiments 2 (Ex Vivo)mentioning

confidence: 99%

Dipeptidyl Peptidase-4 Inhibition Attenuates Arrhythmias via a Protein Kinase A-Dependent Pathway in Infarcted Hearts

Lee

Chen

Chang

2015

Circ J

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Background:The effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on arrhythmias remains unknown. The aim of this study was to investigate whether sitagliptin attenuates arrhythmias through inhibiting nerve growth factor (NGF) expression, focusing on cyclic adenosine monophosphate (cAMP) downstream signaling such as protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). Methods and Results:Male Wistar rats were randomized to either vehicle or sitagliptin for 4 weeks starting 24 h after ligating the coronary artery. Post-infarction was associated with increased oxidative stress. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle-treated rats compared with sham. Compared with the vehicle, infarcted rats treated with sitagliptin had significantly increased cAMP levels, decreased DPP-4 activity, oxidative stress, NGF levels and immunofluorescence-stained sympathetic hyperinnervation. Arrhythmic scores were significantly lower in the sitagliptin-treated infarcted rats than in vehicle. Ex vivo studies showed that sitagliptin increased the phosphorylated cAMP response element-binding protein (CREB), which can be reversed by H-89 (a PKA inhibitor), not brefeldin A (an Epac inhibitor). Heme oxygenase-1 (HO-1) expression was increased by a PKA agonist but not by an Epac agonist. HO-1 expression was attenuated in KG-501 (a CREB inhibitor)-treated infarcted rats in the presence of a PKA agonist. Conclusions:Sitagliptin protects ventricular arrhythmias by attenuating NGF-induced sympathetic innervation via upregulation of HO-1 expression in a cAMP/PKA/CREB-dependent antioxidant pathway in non-diabetic infarcted rats. (Circ J 2015; 79: 2461-2470

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“…Male Wistar rats were subjected to ligation of the anterior descending artery as previously described (28), resulting in infarction of the left ventricular (LV) free wall. Animals were anesthetized with an intraperitoneal injection of ketamine (70 mg/kg).…”

Section: Animalsmentioning

confidence: 99%

“…To confirm that G-CSF administration is effective in improving of cardiac function and remodeling, transthoracic echocardiography was performed using a HP Sonos 5500 system equipped with a 15-6L probe (6 -15 MHz, SONOS 5500, Philips Medical System, Best, The Netherlands) in rats under anesthesia with ketamine (90 mg/kg ip) on days 0 and 56 as previously described (28). M-mode tracing of the LV from the parasternal long-axis view was obtained to measure the LV end-diastolic diameter dimension (LVEDD) and LV end-systolic diameter dimension (LVESD), and fractional shortening (FS; in %) was calculated.…”

Section: Animalsmentioning

confidence: 99%

Granulocyte colony-stimulating factor increases sympathetic reinnervation and the arrhythmogenic response to programmed electrical stimulation after myocardial infarction in rats

Lee¹,

Chen²,

Chang³

2009

American Journal of Physiology-Heart and Circulatory Physiology

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Effect of ATP-Sensitive Potassium Channel Agonists on Ventricular Remodeling in Healed Rat Infarcts

Abstract: Activation of K(ATP) channels by either nicorandil or pinacidil can attenuate ventricular remodeling, probably through a p70S6 kinase-dependent pathway after infarction.

Cited by 51 publications

References 33 publications

ERα on the cell membrane helps the heart

ERα on the cell membrane helps the heart

Dipeptidyl Peptidase-4 Inhibition Attenuates Arrhythmias via a Protein Kinase A-Dependent Pathway in Infarcted Hearts

Granulocyte colony-stimulating factor increases sympathetic reinnervation and the arrhythmogenic response to programmed electrical stimulation after myocardial infarction in rats

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