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Myocardial ischemia and glucose

Bhavisha Bakrania, Joey P Granger, Romain Harmancey
The mammalian heart is a major consumer of ATP and requires a constant supply of energy substrates for contraction. Not surprisingly, alterations of myocardial metabolism have been linked to the development of contractile dysfunction and heart failure. Therefore, unraveling the link between metabolism and contraction should shed light on some of the mechanisms governing cardiac adaptation or maladaptation in disease states. The isolated working rat heart preparation can be used to follow, simultaneously and in real time, cardiac contractile function and flux of energy providing substrates into oxidative metabolic pathways...
September 28, 2016: Journal of Visualized Experiments: JoVE
Yang Li, Jian Li, Zhiwen Hou, Yang Yu, Bo Yu
The primary physiological function of Krüppel-like zinc-finger transcription factor (KLF5) is the regulation of cardiovascular remodeling. Vascular remodeling is closely related to the amelioration of various ischemic diseases. However, the underlying correlation of KLF5 and ischemia is not clear. In this study, we aim to investigate the role of KLF5 in myocardial ischemia reperfusion (IR) injury and the potential mechanisms involved. Cultured H9C2 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/Rep) to mimic myocardial IR injury in vivo...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Liming Yu, Chongxi Fan, Zhi Li, Jian Zhang, Xiaodong Xue, Yinli Xu, Guolong Zhao, Yang Yang, Huishan Wang
Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague-Dawley rats were subjected to MI/R surgery and high glucose (HG, 500 g/L) infusion (4 ml/kg/h) to induce temporary hyperglycemia...
October 18, 2016: Journal of Pineal Research
Wating Su, Yuan Zhang, Qiongxia Zhang, Jinjin Xu, Liying Zhan, Qiqi Zhu, Qingquan Lian, Huimin Liu, Zhong-Yuan Xia, Zhengyuan Xia, Shaoqing Lei
BACKGROUND: Patients with diabetes are prone to develop cardiac hypertrophy and more susceptible to myocardial ischemia-reperfusion (I/R) injury, which are concomitant with hyperglycemia-induced oxidative stress and impaired endothelial nitric oxide (NO) synthase (eNOS)/NO signaling. Caveolae are critical in the transduction of eNOS/NO signaling in cardiovascular system. Caveolin (Cav)-3, the cardiomyocytes-specific caveolae structural protein, is decreased in the diabetic heart in which production of reactive oxygen species are increased...
October 12, 2016: Cardiovascular Diabetology
Mustafa Bilgi, Ahmet Keser, Huseyin Katlandur, Emel Sahin, Ali Osman Kalkan, Murat Yildiz, Aysel Kiyici, Mustafa Keles
INTRODUCTION: Ischemia-modified albumin (IMA) is a marker which can be associated with oxidative stress in various ischemic and non-ischemic processes. Oxidative stress plays roles in diabetes mellitus, its complications and pathogenesis. Serum IMA levels are examined in various clinical events. However, urine IMA levels have not yet been evaluated in diabetic patients. In this study, we aim to examine the relationship between metabolic features and urine microalbuminuria levels of diabetic patients and their urine IMA levels...
October 1, 2016: Journal of Clinical Laboratory Analysis
Abhinav Kanwal, Sujatha Kasetti, Uday Kumar Putcha, Shailendra Asthana, Sanjay K Banerjee
The concept of cardioprotection through preconditioning against ischemia-reperfusion (I/R) injury is well known and established. However, among different proposed mechanisms regarding the concept of ischemic preconditioning, protein kinase C (PKC)-mediated cardioprotection through ischemic preconditioning plays a key role in myocardial I/R injury. Thus, this study was designed to find the relationship between PKC and sodium glucose transporter 1 (SGLT1) in preconditioning-induced cardioprotection, which is ill reported till now...
2016: Drug Design, Development and Therapy
Theodora Tzanavari, Aimilia Varela, Stamatis Theocharis, Elpinickie Ninou, Alkistis Kapelouzou, Dennis V Cokkinos, Maria I Kontaridis, Katia P Karalis
BACKGROUND AND PURPOSE: Metformin administration is associated with myocardial protection during ischemia and/or reperfusion, possibly via inhibition of inflammatory responses in the heart. Exposure to pathogens, in addition to the activation of the immune system and the associated metabolic dysfunction, often results in compromised myocardial function. We examined whether metformin administration could maintain the normal myocardial function in experimental moderate Gram negative infection, induced by lipopolysaccharide (LPS) administration...
October 2016: Metabolism: Clinical and Experimental
Anne Briançon-Marjollet, Denis Monneret, Marion Henri, Marie Joyeux-Faure, Perle Totoson, Sandrine Cachot, Patrice Faure, Diane Godin-Ribuot
What is the central question of this study? This study addresses the relative impact of obesity and intermittent hypoxia in the pathophysiological process of obstructive sleep apnoea by investigating the metabolic, inflammatory and cardiovascular consequences of intermittent hypoxia in lean and obese Zucker rats. What is the main finding and its importance? We found that obesity and intermittent hypoxia have mainly distinct consequences on the investigated inflammatory and cardiometabolic parameters in Zucker rats...
October 5, 2016: Experimental Physiology
Diogo T Galan, Virginie Bito, Piet Claus, Patricia Holemans, Joëlle Abi-Char, Chandan Kadur Nagaraju, Eef Dries, Kristel Vermeulen, Renee Ventura-Clapier, Karin R Sipido, Ronald B Driesen
Scarring and remodeling of the left ventricle (LV) after myocardial infarction (MI) results in ischemic cardiomyopathy with reduced contractile function. Regional differences related to persisting ischemia may exist. We investigated the hypothesis that mitochondrial function and structure is altered in the myocardium adjacent to MI with reduced perfusion (MIadjacent) and less so in the remote, non-ischemic myocardium (MIremote). We used a pig model of chronic coronary stenosis and MI (N=13). Functional and perfusion MR imaging 6 weeks after intervention showed reduced ejection fraction and increased global wall stress compared to sham-operated animals (SHAM; N=14)...
September 9, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Domenico Rendina, Renato Ippolito, Gianpaolo De Filippo, Riccardo Muscariello, Daniela De Palma, Silvana De Bonis, Michele Schiano di Cola, Domenico Benvenuto, Maurizio Galderisi, Pasquale Strazzullo, Ferruccio Galletti
Silent myocardial ischemia (SMI) is frequently observed in patients with essential hypertension (EH). The major risk factor for SMI is uncontrolled blood pressure (BP), but SMI is also observed in patients with well-controlled BP. To evaluate the prevalence of SMI and the factors associated with SMI in EH patients with well-controlled BP. The medical records of 859 EH patients who underwent simultaneous 24-h ambulatory blood pressure monitoring (ABPM) and 24-h ambulatory electrocardiogram recording (AECG) were retrospectively evaluated...
August 26, 2016: Internal and Emergency Medicine
Hong Zhang, Shuang Wu, Hao Liu, Ling Tang, Ruili Du, Yao Chen, Caiyun Xu, Yehua Shen, Shouhong Zhang, Fahuan Song, Kai Zhang, Yunqi Zhu, Zefeng Wang, Weizhong Gu, Ping Liang, Ignasi Carrió, Mei Tian
: This study aims to investigate the in vivo dynamic metabolic changes after induced pluripotent stem cells (iPSCs) and iPSC-derived enriched cardiomyocytes (iPSC-CM) transplantation in a rat model of cardiac ischemia injury. METHODS: Serial positron emission tomography (PET), echocardiography and immunofluorescence studies were performed after iPSCs and iPSC-CM transplantation, and compared to embryonic stem cells (ESCs), ESCs-derived enriched cardiomocytes (ESC-CM) or phosphate-buffered saline (PBS) groups in rats with myocardial infarction...
August 25, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Michael C Y Nam, Christopher D Byrne, Juan Carlos Kaski, Kim Greaves
The role of insulin in the treatment of acute coronary syndrome (ACS) has been widely studied over the past 100 years. The current indication for its use in this context is the treatment of hyperglycemia, irrespective of diabetes, which is associated with adverse outcome. Initial theories proposed that glucose was beneficial in the context of myocardial ischemia and insulin was required to enable glucose cell uptake. However, studies testing this hypothesis with routine insulin administration during ACS have produced disappointing results and research interest has therefore declined...
October 2016: Cardiovascular Drugs and Therapy
Xian-Wei Wang, Fen-Xi Zhang, Fen Yang, Zu-Feng Ding, Nidhi Agarwal, Zhi-Kun Guo, Jawahar L Mehta
AIM: Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors can not only lower blood glucose levels, but also alleviate cardiac remodeling after myocardial ischemia and hypertension. In the present study, we investigated the effects of a DPP-4 inhibitor (linagliptin) and a GLP-1 activator (liraglutide) on glucose- and angiotensin II (Ang II)-induced collagen formation and cytoskeleton reorganization in cardiac fibroblasts in vitro, and elucidated the related mechanisms...
September 2016: Acta Pharmacologica Sinica
Giacinta Guarini, Alda Huqi, Doralisa Morrone, Mario Marzilli
Despite continuous advances in myocardial revascularization procedures and intracoronary devices, patients with ischemic heart disease (IHD) still experience worse prognosis and poor quality of life (QoL). Indeed, chronic stable angina (CSA) is a common disease with a large burden on healthcare costs. Traditionally, CSA is interpreted as episodes of reversible myocardial ischemia related to the presence of stable coronary artery plaque causing myocardial demand/supply mismatch when myocardial oxygen consumption increases...
August 2016: Cardiovascular Drugs and Therapy
Keitaro Nishizawa, Toshiyuki Yano, Masaya Tanno, Takayuki Miki, Atsushi Kuno, Toshiyuki Tobisawa, Makoto Ogasawara, Shingo Muratsubaki, Kouhei Ohno, Satoko Ishikawa, Tetsuji Miura
Chronic kidney disease (CKD) is known to increase myocardial infarct size after ischemia/reperfusion. However, a strategy to prevent the CKD-induced myocardial susceptibility to ischemia/reperfusion injury has not been developed. Here, we examined whether epoetin β pegol, a continuous erythropoietin receptor activator (CERA), normalizes myocardial susceptibility to ischemia/reperfusion injury by its effects on protective signaling and metabolomes in CKD. CKD was induced by 5/6 nephrectomy in rats (subtotal nephrectomy, SNx), whereas sham-operated rats served controls (Sham)...
September 2016: Hypertension
Zi-Ying Shen, Qian Sun, Zhong-Yuan Xia, Qing-Tao Meng, Shao-Qing Lei, Bo Zhao, Ling-Hua Tang, Rui Xue, Rong Chen
Patients with diabetes are more vulnerable to renal ischemia/reperfusion (I/R) injury, which is implicated in hyperglycemia-induced oxidative stress. We previously reported that the hyperglycemia-induced inhibition of DJ-1, a novel oncogene that exhibits potent antioxidant activity, is implicated in the severity of myocardial I/R injury. In the present study, we aimed to explore the role of DJ-1 in hypoxia/reoxygenation (H/R) injury in renal cells exposed to high glucose (HG). For this purpose, NRK-52E cells were exposed to HG (30 mM) for 48 h and then exposed to hypoxia for 4 h and reoxygenation for 2 h, which significantly decreased cell viability and superoxide dismutase (SOD) activity, and increased the malondialdehyde (MDA) content, accompanied by a decrease in DJ‑1 protein expression...
September 2016: International Journal of Molecular Medicine
Jing Yang, Fengyue Wang, Weiju Sun, Yanli Dong, Mingyu Li, Lu Fu
Despite the importance of testosterone as a metabolic hormone, its effects on myocardial metabolism in the ischemic heart remain unclear. Myocardial ischemia leads to metabolic remodeling, ultimately resulting in ATP deficiency and cardiac dysfunction. In the present study, the effects of testosterone replacement on the ischemic heart were assessed in a castrated rat myocardial infarction model established by ligating the left anterior descending coronary artery 2 weeks after castration. The results of real-time PCR and Western blot analyses showed that peroxisome proliferator-activated receptor α (PPARα) decreased in the ischemic myocardium of castrated rats, compared with the sham-castration group, and the mRNA expression of genes involved in fatty acid metabolism (the fatty acid translocase CD36, carnitine palmitoyltransferase I, and medium-chain acyl-CoA dehydrogenase) and glucose transporter-4 also decreased...
2016: PPAR Research
Grete Slettom, Anne K Jonassen, Geir O Dahle, Reinhard Seifert, Terje H Larsen, Rolf K Berge, Jan E Nordrehaug
AIM: Insulin and glucose may have opposite effects when used to reduce ischemia-reperfusion injury. When insulin is administered alone, feeding state determines tolerance and further induces metabolic and hormonal changes. Higher insulin doses are needed for similar activation of cardioprotective Akt signaling in the fed compared to the fasted pig heart. Thus, the aim of the study was to investigate the effects of 2 prespecified insulin doses on infarct size, apoptosis, metabolism, and cardiac function in a clinically relevant, randomized large animal model using conventional percutaneous catheter intervention techniques and including different fasting states...
July 7, 2016: Journal of Cardiovascular Pharmacology and Therapeutics
Christina Drevinge, Knut T Dalen, Maria Nastase Mannila, Margareta Scharin Täng, Marcus Ståhlman, Martina Klevstig, Annika Lundqvist, Ismena Mardani, Fred Haugen, Per Fogelstrand, Martin Adiels, Jorge Asin-Cayuela, Charlotte Ekestam, Jesper R Gådin, Yun K Lee, Hilde Nebb, Sara Svedlund, Bengt R Johansson, Lillemor Mattsson Hultén, Stefano Romeo, Björn Redfors, Elmir Omerovic, Max Levin, Li-Ming Gan, Per Eriksson, Linda Andersson, Ewa Ehrenborg, Alan R Kimmel, Jan Borén, Malin C Levin
BACKGROUND: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. METHODS AND RESULTS: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart...
September 15, 2016: International Journal of Cardiology
Maria K Akhnokh, Feng Hua Yang, Victor Samokhvalov, Kristi L Jamieson, Woo Jung Cho, Cory Wagg, Abhijit Takawale, Xiuhua Wang, Gary D Lopaschuk, Bruce D Hammock, Zamaneh Kassiri, John M Seubert
AIMS: Myocardial ischemia can result in marked mitochondrial damage leading to cardiac dysfunction, as such identifying novel mechanisms to limit mitochondrial injury is important. This study investigated the hypothesis that inhibiting soluble epoxide hydrolase (sEH), responsible for converting epoxyeicosatrienoic acids to dihydroxyeicosatrienoic acids protects mitochondrial from injury caused by myocardial infarction. METHODS: sEH null and WT littermate mice were subjected to surgical occlusion of the left anterior descending (LAD) artery or sham operation...
2016: Frontiers in Pharmacology
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