Reference number : GC-2017-Q1-01956, amendment number : , agreement type : G, recipient legal name : Fonfara, Sonja (University of Guelph), recipient country : CA, recipient province : nan, recipient city : Ontario, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : Feline hypertrophic cardiomyopathy (HCM) is a common, spontaneous disease of adult, predominantly male cats. A genetic cause is reported, but cats can have a mutation and not develop the disease and cats without mutation can present with disease characteristics. Also, other factors that influence the disease are so far not known. HCM is characterized by thickening of the left cardiac chamber wall, with structural and functional changes. This results in increased stiffness and dysfunction of the heart and can cause arrhythmia, thrombus formation and heart failure. However, the clinical signs and progression of the disease are highly variable, and little agreement exists about the clinical and pathological disease parameter. 
Under my leadership, my research team has identified variations in the expression profiles of inflammatory and remodeling mediators in the heart of cats in association with age, gender and HCM. We also observed an increase in cells of a type that we suspect to be stem cells (SC) that invade the heart or grow there. Hence we hypothesize that HCM is driven by remodeling mechanisms resulting from heart muscle cell degeneration causing inflammation and SC mediated compensatory repair processes. 
The long-term objective of my research program is to obtain a dynamic, mechanistic picture of the disease processes in feline HCM. I aim further to investigate factors such as age, obesity, gender and non-cardiac diseases on the structure and function of the heart and to apply these methodologies to other species, with the aim to establish an internationally renowned state-of-the-art research center for cardiovascular research at the University of Guelph. The short term objectives for the next 5 years are to apply novel (RNA sequencing, microRNA analysis, RNA-in situ hybridization) and established (real-time PCR, histology, immunohistology, transmission electron microscopy) techniques to obtain information on genes involved, components in the heart and blood that regulate production of relevant proteins, confirm the production and cellular sources of these proteins, and to characterize de- and regenerative processes, and the potential involvement of SC in these processes. I aim to apply advanced imaging techniques (advanced echocardiography, MRI) to investigate the influence of structural changes on cardiac function. The results obtained will be used to subsequently compare different HCM presentations of cats (i.e with and without thrombi) and investigate prospectively the progression of HCM. 
The proposed project will add substantially to the understanding of relevant mechanisms involved in HCM and the influence of these processes on the function of the heart and thereby the systemic circulation. This interdisciplinary, state-of-the-art approach is unique in small animal cardiology and will have a significant impact on an area of fundamental research in veterinary sciences., program purpose french : Feline hypertrophic cardiomyopathy (HCM) is a common, spontaneous disease of adult, predominantly male cats. A genetic cause is reported, but cats can have a mutation and not develop the disease and cats without mutation can present with disease characteristics. Also, other factors that influence the disease are so far not known. HCM is characterized by thickening of the left cardiac chamber wall, with structural and functional changes. This results in increased stiffness and dysfunction of the heart and can cause arrhythmia, thrombus formation and heart failure. However, the clinical signs and progression of the disease are highly variable, and little agreement exists about the clinical and pathological disease parameter. 
Under my leadership, my research team has identified variations in the expression profiles of inflammatory and remodeling mediators in the heart of cats in association with age, gender and HCM. We also observed an increase in cells of a type that we suspect to be stem cells (SC) that invade the heart or grow there. Hence we hypothesize that HCM is driven by remodeling mechanisms resulting from heart muscle cell degeneration causing inflammation and SC mediated compensatory repair processes. 
The long-term objective of my research program is to obtain a dynamic, mechanistic picture of the disease processes in feline HCM. I aim further to investigate factors such as age, obesity, gender and non-cardiac diseases on the structure and function of the heart and to apply these methodologies to other species, with the aim to establish an internationally renowned state-of-the-art research center for cardiovascular research at the University of Guelph. The short term objectives for the next 5 years are to apply novel (RNA sequencing, microRNA analysis, RNA-in situ hybridization) and established (real-time PCR, histology, immunohistology, transmission electron microscopy) techniques to obtain information on genes involved, components in the heart and blood that regulate production of relevant proteins, confirm the production and cellular sources of these proteins, and to characterize de- and regenerative processes, and the potential involvement of SC in these processes. I aim to apply advanced imaging techniques (advanced echocardiography, MRI) to investigate the influence of structural changes on cardiac function. The results obtained will be used to subsequently compare different HCM presentations of cats (i.e with and without thrombi) and investigate prospectively the progression of HCM. 
The proposed project will add substantially to the understanding of relevant mechanisms involved in HCM and the influence of these processes on the function of the heart and thereby the systemic circulation. This interdisciplinary, state-of-the-art approach is unique in small animal cardiology and will have a significant impact on an area of fundamental research in veterinary sciences., agreement title english : Unraveling the pathophysiology of feline hypertrophic cardiomyopathy - an interdisciplinary approch, agreement title french : Unraveling the pathophysiology of feline hypertrophic cardiomyopathy - an interdisciplinary approch, agreement number : RGPIN, agreement value : 125000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada