Despite progress in diagnosis and treatment lead to a significant reduction of the rate of death attributable to cardiovascular disease (CVD), many efforts must to be done to modify the pathological process and enhance protection. Thus the development of new technologies for diagnosis and novel therapeutic agents is fundamental for clinicians and researcher. In the last decade, murine model had become a useful tool to study CVDs mechanism and to test new pharmacological treatments. Noninvasive imaging technique, specific for laboratory animals, provide the opportunity to image longitudinally the same animal, investigating the follow-up of pathologies and assessing the effect of pharmacological treatments. Aims of this work are to set up an animal model of myocardial infarction (MI) and cardiac imaging (cardiac magnetic resonance imaging and echocardiography) of left ventricle (LV), left atrium (LA) and appendage (LAA) in healthy mice, and then evaluate the global and regional functional-structural changes and remodeling occurring on LV, LA and LAA after MI, with or without pharmacological treatment. The in vivo imaging data were supported by morphological, histological and gene expression analysis. Results from this study described the regional area changes occurring on LV after MI with a progressive loss of contractility also in remote non-infarcted tissue; the presence of only three pulmonary veins entering LA and the presence of the large LAA which, working together with LA, plays an important role in LV filling. After MI not only LV but also LA and LAA remodel in order to maintain, with their enlargement, LV stroke volume. The pharmacological treatment with valsartan, a selective inhibitor of AT1 receptor of Ang II, influenced LV remodeling by reducing LV enlargement, infarct size, ECM gene expression (in particular collagen VIII, fibulin-2 involved in fibrosis and hypertrophy), preserving LV SV without affecting LAA and LA increase in dimension.

EVALUATION OF LEFT VENTRICULAR AND ATRIAL-APPENDAGE FUNCTION IN NORMAL AND ISCHEMIC MOUSE MODELS BY CARDIAC IMAGING TECHNIQUES: A PHARMACOLOGICAL VALIDATION / L. Castiglioni ; tutor: E. Tremoli ; coordinatore: G. Franceschini. - : . UNIVERSITA' DEGLI STUDI DI MILANO, 2013 Jan 18. ((25. ciclo, Anno Accademico 2012. [10.13130/castiglioni-laura_phd2013-01-18].

EVALUATION OF LEFT VENTRICULAR AND ATRIAL-APPENDAGE FUNCTION IN NORMAL AND ISCHEMIC MOUSE MODELS BY CARDIAC IMAGING TECHNIQUES: A PHARMACOLOGICAL VALIDATION

L. Castiglioni
2013-01-18

Abstract

Despite progress in diagnosis and treatment lead to a significant reduction of the rate of death attributable to cardiovascular disease (CVD), many efforts must to be done to modify the pathological process and enhance protection. Thus the development of new technologies for diagnosis and novel therapeutic agents is fundamental for clinicians and researcher. In the last decade, murine model had become a useful tool to study CVDs mechanism and to test new pharmacological treatments. Noninvasive imaging technique, specific for laboratory animals, provide the opportunity to image longitudinally the same animal, investigating the follow-up of pathologies and assessing the effect of pharmacological treatments. Aims of this work are to set up an animal model of myocardial infarction (MI) and cardiac imaging (cardiac magnetic resonance imaging and echocardiography) of left ventricle (LV), left atrium (LA) and appendage (LAA) in healthy mice, and then evaluate the global and regional functional-structural changes and remodeling occurring on LV, LA and LAA after MI, with or without pharmacological treatment. The in vivo imaging data were supported by morphological, histological and gene expression analysis. Results from this study described the regional area changes occurring on LV after MI with a progressive loss of contractility also in remote non-infarcted tissue; the presence of only three pulmonary veins entering LA and the presence of the large LAA which, working together with LA, plays an important role in LV filling. After MI not only LV but also LA and LAA remodel in order to maintain, with their enlargement, LV stroke volume. The pharmacological treatment with valsartan, a selective inhibitor of AT1 receptor of Ang II, influenced LV remodeling by reducing LV enlargement, infarct size, ECM gene expression (in particular collagen VIII, fibulin-2 involved in fibrosis and hypertrophy), preserving LV SV without affecting LAA and LA increase in dimension.
TREMOLI, ELENA
FRANCESCHINI, GUIDO
cardiac imaging ; myocardial infarction ; mouse ; remodeling ; left atrial appendage
Settore BIO/14 - Farmacologia
EVALUATION OF LEFT VENTRICULAR AND ATRIAL-APPENDAGE FUNCTION IN NORMAL AND ISCHEMIC MOUSE MODELS BY CARDIAC IMAGING TECHNIQUES: A PHARMACOLOGICAL VALIDATION / L. Castiglioni ; tutor: E. Tremoli ; coordinatore: G. Franceschini. - : . UNIVERSITA' DEGLI STUDI DI MILANO, 2013 Jan 18. ((25. ciclo, Anno Accademico 2012. [10.13130/castiglioni-laura_phd2013-01-18].
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/215127
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