Fourier transform infrared evaluation of microscopic scarring in the cardiomyopathic heart: effect of chronic AT1 suppression.
Our primary aim was to investigate the use of Fourier transform infrared (FTIR) spectromicroscopy as an accurate assay of cardiac extracellular matrix remodeling. Abnormal rearrangement or remodeling of the cardiac extracellular matrix is known to contribute to cardiac dysfunction. The microscopic multifocal necrosis and scarring are modulated by chronic AT(1) receptor blockade in experimental cardiomyopathy; thus, we also wished to rationalize the spectromicroscopic differences among control, untreated cardiomyopathic (CMP), and losartan-treated cardiomyopathic (LOS) hearts according to the pathogenesis of experimental cardiomyopathy. Male UM-X7.1 cardiomyopathic Syrian hamsters at early and late (65 and 200 days) stages of cardiomyopathy were subjected to 4-week losartan (15 mg/kg/day continuous infusion) treatment. Focal collagen microdomain distribution was confirmed spectroscopically by observation of the collagen IR fingerprint in the 1000-1800 cm(-1) region. Synchrotron FTIR spectromicroscopic map data were obtained from control (F1-beta strain) hamsters, nontreated cardiomyopathic, and losartan-treated CMP animals and imaged with mapping software, according to intensity of collagen fingerprint. Compared to controls, untreated late-stage CMP myocardium was characterized by elevated levels of fibrillar collagens and this was partially normalized with a 4-week losartan treatment. FTIR spectromicroscopy revealed that elevated collagen expression in focal microdomains is present in late-stage cardiomyopathy, and 4-week AT(1) blockade is associated with attenuation of collagen absorption in these lesions.
Gough
Kathleen M
KM
Department of Chemistry, University of Manitoba, Winnipeg, Canada R3T 2N2. kmgough@ms.umanitoba.ca
Zelinski
David
D
Wiens
Richard
R
Rak
Margaret
M
Dixon
Ian M C
IM
D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001391:Azo Compounds; D009202:Cardiomyopathies / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002921:Cicatrix / Q000473:pathology; D003094:Collagen / Q000032:analysis* / Q000378:metabolism; D004396:Coloring Agents; D006224:Cricetinae; D004195:Disease Models, Animal; D004801:Eosine Yellowish-(YS); D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D008297:Male; D008739:Methyl Green; D008867:Microtomy; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D013059:Spectrum Analysis, Raman / Q000379:methods
D047228:Angiotensin II Type 1 Receptor Blockers; D001391:Azo Compounds; D004396:Coloring Agents; D008055:Lipids; C017768:trichrome stain; D008739:Methyl Green; D003094:Collagen; D004801:Eosine Yellowish-(YS)