The long-term objective of this application is to obtain a quantitative description of the extent of myocardial damage induced by chronic coronary artery stenosis in the rat heart. Observations have shown that this disease model produces myocardial lesions of replacement and interstitial fibrosis similar to those found in humans with ischemic coronary artery disease (CAD). The morphometric estimation of these morphological changes combined with measurements of the physiological properties of the heart should contribute to a better understanding of the structural and functional phenomena that characterize CAD. Experiments will be performed with normal rats in order to establish whether: (a) chronic reductions in caliber of the left coronary artery lead to reductions in coronary blood flow (CBF) commensurate to the degree of stenosis and the severity of myocardial injury; and (b) impairment of ventricular function occurs as a result of an imbalance between myocardial damage and the regenerative capacity of the viable mycardium. Since hypertension and hypertrophy represent major risk factors of CAD, coronary constrictions will be made in rats with spontaneous hypertension (SHR) and two-kidney one-clip renal hypertension (RH). The hypotheses to be tested are: (a) that coronary artery stenosis in these animal models will lead to myocardial injury, and alterations of CBF and cardiac function more severe than those in normotensive rats; and (b) that the magnitude of damage will be greater in RH rats than in SHR rats. Normotensive and hypertensive rats will be subjected to coronary artery narrowing with expected reductions in luminal diameter of approximately 30%, 50% and 80%, and the animals will be sacrificed at one and three months after the operation. Morphometric measurements will be made of the degree of coronary narrowing; the percent loss of myocyte nuclei, the extent of fibrosis, the magnitude of myocyte hypertrophy, and the volume, surface area, and length of capillaries. These quantitative parameters will be examined in relation to the functional properties of the ventricle and the alterations in CBF.
| Signore, Sergio; Sorrentino, Andrea; Ferreira-Martins, João et al. (2014) Response to letter regarding article ""Inositol 1,4,5-trisphosphate receptors and human left ventricular myocytes"". Circulation 129:e510-1 |
| Anversa, Piero; Leri, Annarosa; Rota, Marcello et al. (2007) Concise review: stem cells, myocardial regeneration, and methodological artifacts. Stem Cells 25:589-601 |
| Kajstura, Jan; Rota, Marcello; Urbanek, Konrad et al. (2006) The telomere-telomerase axis and the heart. Antioxid Redox Signal 8:2125-41 |
| Kajstura, Jan; Bolli, Roberto; Sonnenblick, Edmund H et al. (2006) Cause of death: suicide. J Mol Cell Cardiol 40:425-37 |
| Anversa, Piero; Leri, Annarosa; Kajstura, Jan (2006) Cardiac regeneration. J Am Coll Cardiol 47:1769-76 |
| Rota, Marcello; LeCapitaine, Nicole; Hosoda, Toru et al. (2006) Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene. Circ Res 99:42-52 |
| Urbanek, Konrad; Torella, Daniele; Sheikh, Farooq et al. (2005) Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci U S A 102:8692-7 |
| Kajstura, Jan; Rota, Marcello; Whang, Brian et al. (2005) Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ Res 96:127-37 |
| Anversa, Piero; Rota, Marcello; Urbanek, Konrad et al. (2005) Myocardial aging--a stem cell problem. Basic Res Cardiol 100:482-93 |
| Linke, Axel; Muller, Patrick; Nurzynska, Daria et al. (2005) Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci U S A 102:8966-71 |
Showing the most recent 10 out of 167 publications
