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Jordan S F Chan
Jordan S F Chan
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Amanda A Greenwell
Amanda A Greenwell
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Christina T Saed
Christina T Saed
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Magnus J Stenlund
Magnus J Stenlund
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Indiresh A Mangra-Bala
Indiresh A Mangra-Bala
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Seyed Amirhossein Tabatabaei Dakhili
Seyed Amirhossein Tabatabaei Dakhili
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Kunyan Yang
Kunyan Yang
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Sally R Ferrari
Sally R Ferrari
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Farah Eaton
Farah Eaton
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Keshav Gopal
Keshav Gopal
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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John R Ussher
John R Ussher
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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-cell function ( Davies et al. 2018 , Diabetes Canada Clinical Practice Guidelines Expert Committee et al. 2018 ). Furthermore, people with early-stage T2D often have undiagnosed and asymptomatic diastolic dysfunction, a key feature of diabetic
F Dong
F Dong
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA.
Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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X Zhang
X Zhang
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA.
Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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X Yang
X Yang
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA.
Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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L B Esberg
L B Esberg
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA.
Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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H Yang
H Yang
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA.
Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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Z Zhang
Z Zhang
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA.
Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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B Culver
B Culver
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA.
Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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J Ren
J Ren
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA.
Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071, USA
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The level of the obese gene product leptin is often positively correlated with body weight, supporting the notion that hyperleptinemia contributes to obesity-associated cardiac dysfunction. However, a link between leptin levels and cardiac function has not been elucidated. This study was designed to examine the role of leptin deficiency (resulting from a point mutation of the leptin gene) in cardiomyocyte contractile function. Mechanical properties and intracellular Ca2 + transients were evaluated in ventricular myocytes from lean control and leptin-deficient ob/ob obese mice at 12 weeks of age. Cardiac ultrastructure was evaluated using transmission electron microscopy. ob/ob mice were overtly obese, hyperinsulinemic, hypertriglycemic, hypoleptinemic and euglycemic. Ultrastructural examination revealed swelling and disorganization of cristae in mitochondria from ob/ob mouse ventricular tissues. Cardiomyocytes from ob/ob mice displayed reduced expression of the leptin receptor Ob-R, larger cross-sectional area, decreased peak shortening and maximal velocity of shortening/relengthening, and prolonged relengthening but not shortening duration compared with lean counterparts. Consistent with mechanical characteristics, myocytes from ob/ob mice displayed reduced intracellular Ca2 + release upon electrical stimulus associated with a slowed intracellular Ca2 + decay rate. Interestingly, the contractile aberrations seen in ob/ob myocytes were significantly improved by in vitro leptin incubation. Contractile dysfunction was not seen in age- and gender-matched high fat-induced obese mice. These results suggested that leptin deficiency contributes to cardiac contractile dysfunction characterized by both systolic and diastolic dysfunction, impaired intracellular Ca2 + hemostasis and ultrastructural derangement in ventricular myocytes.
Daniel Landau
Daniel Landau
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Chen Chayat
Chen Chayat
Department of Pediatrics A, Shraga Segal Department of Microbiology and Immunology, Department of Pathology, Laboratory for Molecular Medicine and Israeli Rat Genome Center, Faculty of Health Sciences, Soroka University Medical Center, Ben Gurion University, PO Box 151, Beer Sheva 84101, Israel
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Nili Zucker
Nili Zucker
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Eli Golomb
Eli Golomb
Department of Pediatrics A, Shraga Segal Department of Microbiology and Immunology, Department of Pathology, Laboratory for Molecular Medicine and Israeli Rat Genome Center, Faculty of Health Sciences, Soroka University Medical Center, Ben Gurion University, PO Box 151, Beer Sheva 84101, Israel
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Channa Yagil
Channa Yagil
Department of Pediatrics A, Shraga Segal Department of Microbiology and Immunology, Department of Pathology, Laboratory for Molecular Medicine and Israeli Rat Genome Center, Faculty of Health Sciences, Soroka University Medical Center, Ben Gurion University, PO Box 151, Beer Sheva 84101, Israel
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Yoram Yagil
Yoram Yagil
Department of Pediatrics A, Shraga Segal Department of Microbiology and Immunology, Department of Pathology, Laboratory for Molecular Medicine and Israeli Rat Genome Center, Faculty of Health Sciences, Soroka University Medical Center, Ben Gurion University, PO Box 151, Beer Sheva 84101, Israel
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Yael Segev
Yael Segev
Department of Pediatrics A, Shraga Segal Department of Microbiology and Immunology, Department of Pathology, Laboratory for Molecular Medicine and Israeli Rat Genome Center, Faculty of Health Sciences, Soroka University Medical Center, Ben Gurion University, PO Box 151, Beer Sheva 84101, Israel
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in the form of both diastolic and systolic dysfunction and of structural abnormalities ( Marwick 2006 ). In asymptomatic diabetic patients, diastolic dysfunction appears to be, in fact, very common ( Zabalgoitia et al . 2001 ). Since hypertension is
Shi-Yan Li
Shi-Yan Li
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA
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Cindy X Fang
Cindy X Fang
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA
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Nicholas S Aberle II
Nicholas S Aberle II
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA
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Bonnie H Ren
Bonnie H Ren
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA
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Asli F Ceylan-Isik
Asli F Ceylan-Isik
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA
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Jun Ren
Jun Ren
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071, USA
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Introduction Glucose toxicity contributes to development of diabetic cardiomyopathy characterized by systolic and diastolic dysfunctions independent of coronary macro- and micro-vascular diseases ( Galderisi et al. 1991 , Ren et
Morag J Young
Morag J Young
Baker Heart and Diabetes Institute, Prahran, Australia
Hudson Institute of Medical Research, Clayton, Australia
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Hudson Institute of Medical Research, Clayton, Australia
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Colin D Clyne
Colin D Clyne
Hudson Institute of Medical Research, Clayton, Australia
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Karen E Chapman
Karen E Chapman
The University/BHF Centre for Cardiovascular Science, The University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK
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the MR are markedly affected by sex hormones. The cardiac tissue RAAS, aldosterone/MR activation and circulating RAAS all contribute to the onset of diastolic dysfunction, which is more common in older women as a result of hypertension and lower E2
Jordan S F Chan
Jordan S F Chan
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Tanin Shafaati
Tanin Shafaati
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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John R Ussher
John R Ussher
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada
Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada
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studies. Intriguingly, using a mouse model in which myocardial glucose oxidation is abolished due to cardiac-specific deletion of PDH ( Gopal et al. 2018 ), treatment with liraglutide can no longer alleviate diastolic dysfunction when these animals are
Zhenhua Li
Zhenhua Li
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Tao Zhang
Tao Zhang
Department of Cardiology, Department of Orthopedic, Department of Cardiology, Qilu Hospital of Shandong University, Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education and Ministry of Health, Jinan 250012, China
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Hongyan Dai
Hongyan Dai
Department of Cardiology, Department of Orthopedic, Department of Cardiology, Qilu Hospital of Shandong University, Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education and Ministry of Health, Jinan 250012, China
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Guanghui Liu
Guanghui Liu
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Haibin Wang
Haibin Wang
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Yingying Sun
Yingying Sun
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Yun Zhang
Yun Zhang
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Zhiming Ge
Zhiming Ge
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that is arbitrarily defined as 1. Data are shown as mean± s.d. * P <0.05 versus normal rat. Discussion Diabetic cardiomyopathy is characterized by both systolic and diastolic dysfunction ( Galderisi 2006 ). In this current study, we established type 1
Jennifer J DuPont
Jennifer J DuPont
Molecular Cardiology Research Institute, Tufts Medical Center, Boston
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Iris Z Jaffe
Iris Z Jaffe
Molecular Cardiology Research Institute, Tufts Medical Center, Boston
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diastolic dysfunction ( Jia et al. 2015 , 2016 , Rickard et al. 2014 ) Pulmonary HTN Unclear Pulmonary vascular remodeling and increase right ventricular systolic pressure ( Maron et al. 2013 , Preston et al. 2013 ) Cerebral
Timothy J Cole
Timothy J Cole
Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Monash Medical Centre, Clayton, Victoria, Australia
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Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Monash Medical Centre, Clayton, Victoria, Australia
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Morag J Young
Morag J Young
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Monash Medical Centre, Clayton, Victoria, Australia
Department of Molecular and Translational Research, Monash University, Melbourne, Victoria, Australia
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Department of Molecular and Translational Research, Monash University, Melbourne, Victoria, Australia
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responses were similarly assessed following 16 weeks of a high-fat diet by another group who demonstrated that EC-MR play a key role in the activation of cardiac inflammatory and pro-fibrotic responses leading to cardiac diastolic dysfunction and aortic
Elena Grossini
Elena Grossini
Laboratory of Physiology and Experimental Surgery, Pediatric Unit, Department of Translational Medicine, University Eastern Piedmont ‘A. Avogadro’, Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carita, Corso Mazzini 36, I-28100 Novara, Italy
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Flavia Prodam
Flavia Prodam
Laboratory of Physiology and Experimental Surgery, Pediatric Unit, Department of Translational Medicine, University Eastern Piedmont ‘A. Avogadro’, Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carita, Corso Mazzini 36, I-28100 Novara, Italy
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Gillian Elisabeth Walker
Gillian Elisabeth Walker
Laboratory of Physiology and Experimental Surgery, Pediatric Unit, Department of Translational Medicine, University Eastern Piedmont ‘A. Avogadro’, Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carita, Corso Mazzini 36, I-28100 Novara, Italy
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Lorenzo Sigaudo
Lorenzo Sigaudo
Laboratory of Physiology and Experimental Surgery, Pediatric Unit, Department of Translational Medicine, University Eastern Piedmont ‘A. Avogadro’, Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carita, Corso Mazzini 36, I-28100 Novara, Italy
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Serena Farruggio
Serena Farruggio
Laboratory of Physiology and Experimental Surgery, Pediatric Unit, Department of Translational Medicine, University Eastern Piedmont ‘A. Avogadro’, Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carita, Corso Mazzini 36, I-28100 Novara, Italy
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Kevin Bellofatto
Kevin Bellofatto
Laboratory of Physiology and Experimental Surgery, Pediatric Unit, Department of Translational Medicine, University Eastern Piedmont ‘A. Avogadro’, Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carita, Corso Mazzini 36, I-28100 Novara, Italy
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Patrizia Marotta
Patrizia Marotta
Laboratory of Physiology and Experimental Surgery, Pediatric Unit, Department of Translational Medicine, University Eastern Piedmont ‘A. Avogadro’, Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carita, Corso Mazzini 36, I-28100 Novara, Italy
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Claudio Molinari
Claudio Molinari
Laboratory of Physiology and Experimental Surgery, Pediatric Unit, Department of Translational Medicine, University Eastern Piedmont ‘A. Avogadro’, Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carita, Corso Mazzini 36, I-28100 Novara, Italy
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David Mary
David Mary
Laboratory of Physiology and Experimental Surgery, Pediatric Unit, Department of Translational Medicine, University Eastern Piedmont ‘A. Avogadro’, Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carita, Corso Mazzini 36, I-28100 Novara, Italy
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Gianni Bona
Gianni Bona
Laboratory of Physiology and Experimental Surgery, Pediatric Unit, Department of Translational Medicine, University Eastern Piedmont ‘A. Avogadro’, Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carita, Corso Mazzini 36, I-28100 Novara, Italy
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Giovanni Vacca
Giovanni Vacca
Laboratory of Physiology and Experimental Surgery, Pediatric Unit, Department of Translational Medicine, University Eastern Piedmont ‘A. Avogadro’, Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carita, Corso Mazzini 36, I-28100 Novara, Italy
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showing an association between low plasma adiponectin and a worsened diastolic dysfunction ( Negi et al . 2012 ). The results obtained about −d P /d t max and those regarding myocardial oxygen metabolism are of particular relevance and strengthen the
