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Myocardial ischemia and glucose

Chunyan Wang, Haobo Li, Sheng Wang, Xiaowen Mao, Dan Yan, Stanley S Wong, Zhengyuan Xia, Michael G Irwin
BACKGROUND/AIMS: Protein kinase C(PKC)-ε activation is a mechanism of preconditioning cardioprotection but its role in repeated non-invasive limb ischemic preconditioning (rNLIP) mediated cardioprotection against myocardial ischemia/reperfusion (I/R) injury in diabetes is unknown. METHODS: Eight-week streptozotocin-induced diabetic and non-diabetic Sprague-Dawley rats were subjected to I/R without or with rNLIP. In vitro, H9C2 cells were cultured with high glucose (HG) and subjected to hypoxia/re-oxygenation (H/R) without or with PKC-ε or STAT3 gene knock-down in the absence or presence of remote time hypoxia preconditioning (HPC)...
March 7, 2018: Cellular Physiology and Biochemistry
Kristina K Durham, Kevin M Chathely, Bernardo L Trigatti
The cardioprotective lipoprotein HDL prevents myocardial infarction , and cardiomyocyte death due to ischemia/reperfusion injury .  The scavenger receptor class B, type 1 (SR-B1) is a high affinity HDL receptor and has been shown to mediate HDL dependent lipid transport as well as signaling in a variety of different cell types.  The contribution of SR-B1 in cardiomyocytes to the protective effects of HDL on cardiomyocyte survival following ischemia has not yet been studied.  Here we use a model of simulated ischemia (oxygen and glucose deprivation; OGD), to assess the mechanistic involvement of SR-B1, PI3K, and AKT in HDL mediated protection of cardiomyocytes from cell death...
March 9, 2018: Biochemical Journal
Guo-Qiang Yuan, Song Gao, Yong-Jian Geng, Yao-Ping Tang, Min-Juan Zheng, Harnath S Shelat, Scott Collins, Han-Jing Wu, Yi-Ling Wu
Background: Our previous studies have shown that Tongxinluo (TXL), a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether TXL can improve hypercholesterolemia-impaired heart function by protecting artery endothelial function and increasing microvascular density (MVD) in heart. Furthermore, we will explore the underlying molecular mechanism of TXL cardiovascular protection...
March 5, 2018: Chinese Medical Journal
Leon Varjabedian, Mohammad Bourji, Leili Pourafkari, Nader D Nader
Metformin is a biguanide that is widely used as an insulin-sparing agent to treat diabetes. When compared with the general population, diabetics are twice as likely to die from fatal myocardial infarction and congestive heart failure (CHF). There has been a significant concern regarding the use of metformin in patients with CHF because of their higher tendency to develop lactic acidosis. However, large epidemiological trials have reported better cardiovascular prognosis with metformin compared to other glucose-lowering agents among diabetics...
February 24, 2018: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Marie Vognstoft Hjortbak, Johanne Hjort, Jonas Agerlund Povlsen, Rebekka Vibjerg Jensen, Nicolaj Brejnholdt Støttrup, Mia R Laursen, Nichlas Riise Jespersen, Bo Løfgren, Hans Erik Bøtker
Augmented mortality and morbidity following an acute myocardial infarction in patients with diabetes mellitus Type 2 (T2DM) may be caused by increased sensitivity to ischemia reperfusion (IR) injury or altered activation of endogenous cardioprotective pathways modified by T2DM per se or ischemic preconditioning (IPC). We aimed to investigate, whether the duration of T2DM influences sensitivity against IR injury and the efficacy of IPC, and how myocardial glucose oxidation rate was involved. Male Zucker diabetic fatty rats (homozygote (fa/fa)) at ages 6-(prediabetic), 12- (onset diabetes) and 24-weeks of age (late diabetes) and their age-matched non-diabetic controls (heterozygote (fa/+) were subjected to IR injury in the Langendorff model and randomised to IPC stimulus or control...
2018: PloS One
Myoung-Gwi Ryou, Robert T Mallet
Ischemia-reperfusion syndromes of the heart and brain are the leading cause of death and long-term disability worldwide. Development of effective treatments for myocardial infarction, stroke, cardiac arrest and their sequelae requires preclinical models that replicate specific features of ischemia-reperfusion. The complexities of intact animals, including the integrated function of organ systems, autonomic innervation and endocrine factors, often preclude detailed study of specific components of ischemia-reperfusion injury cascades...
2018: Methods in Molecular Biology
Rosanna Di Paola, Roberta Fusco, Enrico Gugliandolo, Ramona D'Amico, Michela Campolo, Saverio Latteri, Arianna Carughi, Giuseppina Mandalari, Salvatore Cuzzocrea
Diabetes mellitus is an important risk factor for the development of heart pathology. Myocardial infarction is the cause of death occurring after prolonged ischemia of the coronary arteries. Restoration of blood flow is the first intervention against heart attack, although the process of restoring blood flow to the ischemic myocardium could cause additional injury. This phenomenon, termed myocardial ischemia-reperfusion (MI-R) injury, is characterized by the formation of oxygen radicals. Pistachios have significant glucose- and insulin-lowering effects and can improve the inflammatory contest by downregulating both the expression and the circulating levels of several metabolic risk markers...
2018: Frontiers in Pharmacology
Xiaowu Wang, Binbin Yuan, Biao Cheng, Ying Liu, Ben Zhang, Xianyue Wang, Xi Lin, Bo Yang, Gu Gong
Endoplasmic reticulum (ER) stress is associated with ischemia/reperfusion (I/R)-induced cardiomyocyte apoptosis. Crocin could protect myocardial cells against I/R injury and suppress ER stress. This study aimed to explore the molecular mechanism of crocin related to ER stress in myocardial I/R injury. We found crocin alleviated I/R-induced cardiomyocyte apoptosis both in I/R-induced primary cardiomyocytes and in mouse models. The expression of Bax, active caspase 3, Glucose-regulated protein of 78 kDa (GRP78), and C/EBP homologous protein (CHOP) induced by I/R injury was reduced, whereas Bcl-2 expression was enhanced by crocin, the effect of which was abrogated by ER stress activator thapsigargin treatment...
February 8, 2018: Shock
Yun Wu, Fen Liu, Xiang Ma, Dilare Adi, Ming-Tao Gai, Xiang Jin, Yi-Ning Yang, Ying Huang, Xiang Xie, Xiao-Mei Li, Zhen-Yan Fu, Bang-Dang Chen, Yi-Tong Ma
The proteome profile changes after acute myocardial infarction (AMI) and the roles played by important protein species remain poorly understood. Here, we constructed a mouse AMI model by ligating the left coronary artery of male C57B/6J mice to investigate the molecular changes after AMI on the protein level. Total proteins of the left ventricle were extracted and quantitatively analyzed by isobaric tags using relative and absolute quantitation (iTRAQ) technologies. The transcript and protein levels of important genes were further validated using quantitative polymerase chain reaction and western blot...
January 5, 2018: Oncotarget
Hailey A Houson, Gregory N Nkepang, Andria F Hedrick, Vibhudutta Awasthi
Positron emission tomography (PET) of myocardial infarction (MI) by infarct avid imaging has the potential to reduce the time to diagnosis and improve diagnostic accuracy. The objective of this work was to synthesize 18 F-labeled glucaric acid (FGA) for PET imaging of isoproterenol-induced cardiomyopathy in a rat model. METHODS: We synthesized 18 F-FGA by controlled oxidation of 18 F-fluorodeoxy glucose (FDG), mediated by 4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) in presence of NaBr and NaOCl in highly-buffered reaction conditions...
December 27, 2017: Nuclear Medicine and Biology
Hong Li, Tong Zou, Shuai Meng, Yun-Zhu Peng, Jie-Fu Yang
Ischemic heart disease is a major health threat, resulting in a large number of mortalities annually worldwide. Oxidative stress is one of the main causes of cell death during ischemia‑reperfusion (IR) injury. Cyclin dependent kinase inhibitor 1A (known as p21) is important in protecting tissues against IR injury, however the mechanism remains unknown. In the present study, oxygen‑glucose deprivation and subsequent reoxygenation (OGD/R) in H9c2 heart‑derived myocytes was used as a model to study myocardial IR injury in vitro...
January 5, 2018: Molecular Medicine Reports
John R Ussher, Jonathan E Campbell, Erin E Mulvihill, Laurie L Baggio, Holly E Bates, Brent A McLean, Keshav Gopal, Megan Capozzi, Bernardo Yusta, Xiemin Cao, Safina Ali, Minsuk Kim, M Golam Kabir, Yutaka Seino, Jinya Suzuki, Daniel J Drucker
Incretin hormones exert pleiotropic metabolic actions beyond the pancreas. Although the heart expresses both incretin receptors, the cardiac biology of GIP receptor (GIPR) action remains incompletely understood. Here we show that GIPR agonism did not impair the response to cardiac ischemia. In contrast, genetic elimination of the Gipr reduced myocardial infarction (MI)-induced ventricular injury and enhanced survival associated with reduced hormone sensitive lipase (HSL) phosphorylation; it also increased myocardial triacylglycerol (TAG) stores...
February 6, 2018: Cell Metabolism
Lei Zhang, Ting-Ting Wei, Yong Li, Jing Li, Yong Fan, Feng-Qing Huang, Yuan-Yuan Cai, Gaoxiang Ma, Jin-Feng Liu, Qian-Qian Chen, Shi-Lei Wang, Honglin Li, Raphael N Alolga, Baolin Liu, Dong-Sheng Zhao, Jian-Hua Shen, Xiang-Ming Wang, Wei Zhu, Ping Li, Lian-Wen Qi
Background -As new biomarkers of coronary artery diseases (CAD) emerge via metabolomics, the underlying functional mechanisms remain to be elucidated. Functional metabolomics aims to translate metabolomics-derived biomarkers to disease mechanisms. Methods -A cohort of 2324 patients who underwent coronary angiography from 4 independent centers was studied. A combination of ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) in the negative ion mode was employed for untargeted analysis of metabolites in plasma...
December 6, 2017: Circulation
Li-Ming Yu, Wen-Cheng Di, Xue Dong, Zhi Li, Yong Zhang, Xiao-Dong Xue, Yin-Li Xu, Jian Zhang, Xiong Xiao, Jin-Song Han, Yu Liu, Yang Yang, Hui-Shan Wang
It has been demonstrated that the anti-oxidative and cardioprotective effects of melatonin are, at least in part, mediated by its membrane receptors. However, the direct downstream signaling remains unknown. We previously found that melatonin ameliorated myocardial ischemia-reperfusion (MI/R) injury in diabetic animals, although the underlying mechanisms are also incompletely understood. This study was designed to determine the role of melatonin membrane receptors in melatonin's cardioprotective actions against diabetic MI/R injury with a focus on cGMP and its downstream effector PKG...
February 2018: Biochimica et Biophysica Acta
Uyanga Batnyam, Nway Ko Ko, Aamir Javaid
Diabetes mellitus is one of the most common modifiable risk factors for coronary artery disease, and its prevalence is rising globally. Persistent hyperglycemia has a well-established cardiovascular risk, and its treatment plays an important role in the prevention of future cardiovascular events. While we improved microvascular complications such as retinopathy, nephropathy, and neuropathy by stringent blood glucose control, the cardiovascular morbidity and mortality in diabetics remain high. Hypoglycemia, on the other hand, is an important side effect of pharmaceutical blood glucose control, especially those who are treated with insulin...
September 25, 2017: Curēus
Ming-Hsien Chiang, Chan-Jung Liang, Chen-Wei Liu, Bo-Jhih Pan, Wen-Ping Chen, Yi-Fan Yang, I-Ta Lee, Jaw-Shiun Tsai, Chiang-Wen Lee, Yuh-Lien Chen
Aliskiren is a direct renin inhibitor that has been effective in anti-hypertension. We investigated whether aliskiren could improve the ischemia-induced cardiac injury and whether the autophagy was involved in this effect. A myocardial infarction (MI) model was created by the ligation of the left anterior coronary artery in C57J/BL6 mice. They were treated for 1, 3, 7, and 14 days with vehicle or aliskiren (25 mg/kg/day via subcutaneous injection). In vivo , the MI mice exhibited worse cardiac function by echocardiographic assessment and showed larger myocardial scarring by light microscopy, whereas aliskiren treatment reversed these effects, which were also associated with the changes in caspase-3 and Bcl-2 expression as well as in the number of apoptotic cells...
2017: Frontiers in Pharmacology
Marija Bakovic, Natalija Filipovic, Lejla Ferhatovic Hamzic, Nenad Kunac, Elena Zdrilic, Marija Vitlov Uljevic, Sandra Kostic, Livia Puljak, Katarina Vukojevic
Changes in sensory and sympathetic innervation during diabetes mellitus (DM) can be a predictor of arrhythmias, silent myocardial ischemia, and chronic heart failure, but knowledge about these changes is still unsatisfactory. We analyzed whether prolonged DM induces changes in density of sensory and sympathetic nerve terminals of rat's heart and whether it contributes to cardiomyopathy during aging. DM was induced by i/p injecting 55 mg/kg streptozotocin to male Sprague-Dawley rats, while a control group received a citrate buffer...
January 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Robert T Mallet, Albert H Olivencia-Yurvati, Rolf Bünger
Cardiac contractile function is adenosine-5'-triphosphate (ATP)-intensive, and the myocardium's high demand for oxygen and energy substrates leaves it acutely vulnerable to interruptions in its blood supply. The myriad cardioprotective properties of the natural intermediary metabolite pyruvate make it a potentially powerful intervention against the complex injury cascade ignited by myocardial ischemia-reperfusion. A readily oxidized metabolic substrate, pyruvate augments myocardial free energy of ATP hydrolysis to a greater extent than the physiological fuels glucose, lactate and fatty acids, particularly when it is provided at supra-physiological plasma concentrations...
January 2018: Experimental Biology and Medicine
Zsófia Meiszterics, Attila Kónyi, Gábor Hild, Zsolt Sárszegi, Balázs Gaszner
Aim & methods: This 6-month prospective, observational, noninterventional, open-label clinical study assessed the effectiveness/safety of trimetazidine in 737 patients with stable angina pectoris and Type 2 diabetes mellitus (OGYI/51534-1/2014). RESULTS: Trimetazidine-based therapy was effective in stable coronary artery disease, with significant improvements from baseline (p < 0.05) in: number of angina attacks/week (2.9 ± 2.4 vs 1.1 ± 1.6), angina severity (Canadian Cardiovascular Society Classification 1...
November 2017: Journal of Comparative Effectiveness Research
Pongpan Tanajak, Piangkwan Sa-Nguanmoo, Sivaporn Sivasinprasan, Savitree Thummasorn, Natthaphat Siri-Angkul, Siriporn Chattipakorn, Nipon Chattipakorn
Sodium-glucose cotransporter 2 inhibitor (SGLT2-i) effects on cardiac ischemia/reperfusion (I/R) injury are unclear. Unlike SGLT2-i, dipeptidyl peptidase 4 inhibitors (DPP4-i) have shown effective cardioprotection in cardiac I/R injury. We aimed to investigate whether SGLT2-i reduces myocardial dysfunction and myocardial injury to a greater extent than DPP4-i in obese-insulin resistant rats with/without cardiac I/R injury. The high fat (HF) diet induced obese-insulin resistant rats were divided into 4 groups and received the following treatments for 28 days: vehicle (HFV); vildagliptin at a dosage of 3 mg/kg/day (HFVil); dapagliflozin at a dosage of 1 mg/kg/day (HFDa); and combination drugs (HFDaVil)...
November 15, 2017: Journal of Endocrinology
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