Background: The CARD scaffold family members, named for containing the common caspase-recruitment... more Background: The CARD scaffold family members, named for containing the common caspase-recruitment domain, are important modulators of inflammatory and apoptotic signalling. CARD11, a membrane bound scaffold, is essential for the production of cytokines in the immune cellular response but is present in heart and lung tissue, where its effects are unknown, and described to associate with apoptotic players such as BCL10 and caspase-8. Due to the complex nature of cardiac response to myocardial infarction (MI), we hypothesize that CARD11 can act as a modulator and integrator of receptor mediated apoptotic pathways following cardiac tissue injury. Methods & Results: CARD11 expression was increased in neonatal cardiomyocytes by general stress induction by H2O2 (25μM) and death receptor activation by Fas agonist Jo2 (1μg/ml) and TNF-alpha (50ng/ml) in isolated neonatal cardiomyocytes. Annexin V (AV) and propidium iodide (PI) double staining demonstrated decreased levels of apoptotic cells (AV+/PI+) following H2O...
Infections are thought to be important in the pathogenesis of many heart diseases. Coxsackievirus... more Infections are thought to be important in the pathogenesis of many heart diseases. Coxsackievirus B3 (CVB3) has been linked to chronic dilated cardiomyopathy, a common cause of progressive heart disease, heart failure and sudden death. We show here that the sarcoma (Src) family kinase Lck (p56lck) is required for efficient CVB3 replication in T-cell lines and for viral replication and persistence in vivo. Whereas infection of wild-type mice with human pathogenic CVB3 caused acute and very severe myocarditis, meningitis, hepatitis, pancreatitis and dilated cardiomyopathy, mice lacking the p56lck gene were completely protected from CVB3-induced acute pathogenicity and chronic heart disease. These data identify a previously unknown function of Src family kinases and indicate that p56lck is the essential host factor that controls the replication and pathogenicity of CVB3.
In viral myocarditis, inflammation and destruction of cardiac myocytes leads to fibrosis, causing... more In viral myocarditis, inflammation and destruction of cardiac myocytes leads to fibrosis, causing progressive impairment in cardiac function. Here we show the etiologic importance of serine elastase activity in the pathophysiology of acute viral myocarditis and the therapeutic ...
Journal of the American College of Cardiology, 1995
... A. Shakir Pandey, Michael J. Sole, John S. Floras, Fayez Dawood, Wen-Hu Wen, Lily Wee, Peter ... more ... A. Shakir Pandey, Michael J. Sole, John S. Floras, Fayez Dawood, Wen-Hu Wen, Lily Wee, Peter Liu. ... However it was still depressed when compared to C. EF LMMI LVEDP LVEDVI T b C 64 86 11 86 45 11 FU FU FU FU FU FU PI 48"52" 148*"122" 18*"13 146*"128" 103*"59â ...
Endothelin-1 (ET-1) is known to have positive inotropic effects in isolated cardiac muscle strips... more Endothelin-1 (ET-1) is known to have positive inotropic effects in isolated cardiac muscle strips. ET-1 levels are elevated in congestive heart failure (CHF). We investigated the effects of ET-1 on contractility and cardiac relaxation (lusitropy) of the intact healthy murine heart and myocarditic/cardiomyopathic heart by chronic oral treatment with a mixed ETA/ETB blocker SB217242. Chronic ET-1 blockade of normal hearts resulted in depression of contractility and lusitropy of the normal heart but preservation and enhancement of contractility and lusitropy in myocarditic animals, in which ET-1 cardiac content is elevated. This suggests that ET-1 is important in the basal contractility and relaxation of the normal heart but that its chronic elevation in CHF causes impairment of cardiac systolic and diastolic performance.
c-Kit Receptor is Essential for Functional Cardiac Repair Post-Myocardial Infarction Bilal Ayach,... more c-Kit Receptor is Essential for Functional Cardiac Repair Post-Myocardial Infarction Bilal Ayach, Makoto Yoshimitsu, Christopher Siatskas, Paul Lee, Hilda Lim, Fayez Dawood, Manyin Chen, Jeffrey A. Medin, Peter P. Liu; Medicine, The Heart and Stroke/Richard Lewar Centre of Excellence, Toronto, ON, Canada; Ontario Cancer Institute of the University Health Network, Toronto, ON, Canada; The University of Toronto, Toronto, ON, Canada
Background: The CARD scaffold family members, named for containing the common caspase-recruitment... more Background: The CARD scaffold family members, named for containing the common caspase-recruitment domain, are important modulators of inflammatory and apoptotic signalling. CARD11, a membrane bound scaffold, is essential for the production of cytokines in the immune cellular response but is present in heart and lung tissue, where its effects are unknown, and described to associate with apoptotic players such as BCL10 and caspase-8. Due to the complex nature of cardiac response to myocardial infarction (MI), we hypothesize that CARD11 can act as a modulator and integrator of receptor mediated apoptotic pathways following cardiac tissue injury. Methods & Results: CARD11 expression was increased in neonatal cardiomyocytes by general stress induction by H2O2 (25μM) and death receptor activation by Fas agonist Jo2 (1μg/ml) and TNF-alpha (50ng/ml) in isolated neonatal cardiomyocytes. Annexin V (AV) and propidium iodide (PI) double staining demonstrated decreased levels of apoptotic cells (AV+/PI+) following H2O...
Infections are thought to be important in the pathogenesis of many heart diseases. Coxsackievirus... more Infections are thought to be important in the pathogenesis of many heart diseases. Coxsackievirus B3 (CVB3) has been linked to chronic dilated cardiomyopathy, a common cause of progressive heart disease, heart failure and sudden death. We show here that the sarcoma (Src) family kinase Lck (p56lck) is required for efficient CVB3 replication in T-cell lines and for viral replication and persistence in vivo. Whereas infection of wild-type mice with human pathogenic CVB3 caused acute and very severe myocarditis, meningitis, hepatitis, pancreatitis and dilated cardiomyopathy, mice lacking the p56lck gene were completely protected from CVB3-induced acute pathogenicity and chronic heart disease. These data identify a previously unknown function of Src family kinases and indicate that p56lck is the essential host factor that controls the replication and pathogenicity of CVB3.
In viral myocarditis, inflammation and destruction of cardiac myocytes leads to fibrosis, causing... more In viral myocarditis, inflammation and destruction of cardiac myocytes leads to fibrosis, causing progressive impairment in cardiac function. Here we show the etiologic importance of serine elastase activity in the pathophysiology of acute viral myocarditis and the therapeutic ...
Journal of the American College of Cardiology, 1995
... A. Shakir Pandey, Michael J. Sole, John S. Floras, Fayez Dawood, Wen-Hu Wen, Lily Wee, Peter ... more ... A. Shakir Pandey, Michael J. Sole, John S. Floras, Fayez Dawood, Wen-Hu Wen, Lily Wee, Peter Liu. ... However it was still depressed when compared to C. EF LMMI LVEDP LVEDVI T b C 64 86 11 86 45 11 FU FU FU FU FU FU PI 48"52" 148*"122" 18*"13 146*"128" 103*"59â ...
Endothelin-1 (ET-1) is known to have positive inotropic effects in isolated cardiac muscle strips... more Endothelin-1 (ET-1) is known to have positive inotropic effects in isolated cardiac muscle strips. ET-1 levels are elevated in congestive heart failure (CHF). We investigated the effects of ET-1 on contractility and cardiac relaxation (lusitropy) of the intact healthy murine heart and myocarditic/cardiomyopathic heart by chronic oral treatment with a mixed ETA/ETB blocker SB217242. Chronic ET-1 blockade of normal hearts resulted in depression of contractility and lusitropy of the normal heart but preservation and enhancement of contractility and lusitropy in myocarditic animals, in which ET-1 cardiac content is elevated. This suggests that ET-1 is important in the basal contractility and relaxation of the normal heart but that its chronic elevation in CHF causes impairment of cardiac systolic and diastolic performance.
c-Kit Receptor is Essential for Functional Cardiac Repair Post-Myocardial Infarction Bilal Ayach,... more c-Kit Receptor is Essential for Functional Cardiac Repair Post-Myocardial Infarction Bilal Ayach, Makoto Yoshimitsu, Christopher Siatskas, Paul Lee, Hilda Lim, Fayez Dawood, Manyin Chen, Jeffrey A. Medin, Peter P. Liu; Medicine, The Heart and Stroke/Richard Lewar Centre of Excellence, Toronto, ON, Canada; Ontario Cancer Institute of the University Health Network, Toronto, ON, Canada; The University of Toronto, Toronto, ON, Canada
Uploads