Cellular and extracellular remodeling with the development and recovery from tachycardia-induced cardiomyopathy: changes in fibrillar collagen, myocyte adhesion capacity and proteoglycans.
The myocardial extracellular matrix (ECM) is composed of three important constituents: (1) fibrillar collagen, (2) a basement membrane, and (3) proteoglycans. Structural or compositional changes in these ECM components may affect left ventricular (LV) function as well as influence overall LV geometry. Accordingly, this study examined the relationship between changes in these ECM components to changes in LV function and geometry which develop with the progression and regression from supraventricular tachycardia-induced cardiomyopathy (SVT). LV function and specific components of the ECM were studied in pigs with SVT cardiomyopathy (SVT:atrially paced 240 bpm, 3 weeks; n = 7), or after a 4-week recovery from SVT cardiomyopathy (post-SVT; n = 6), and in controls (n = 7). LV fractional shortening fell by 60% and end-diastolic dimension increased by 47% with SVT compared to controls. While LV fractional shortening normalized with post-SVT, end-diastolic dimension remained 40% higher than controls. Collagen concentration fell by 22% and salt extractable collagen, which reflects collagen cross-linking, increased by 41% with SVT compared to controls. Collagen concentration increased by 20%, collagen extraction normalized, and levels of collagen type III mRNA increased by 42% with post-SVT. Isolated myocyte adhesion capacity to basement membrane substrates laminin, fibronectin, and collagen type IV were examined. SVT resulted in over a 50% reduction in myocyte adhesion for all of the basement membrane components compared to controls. A normalization in isolated myocyte adhesion capacity was observed in post-SVT. The relative content and distribution of the ECM proteoglycan chondroitin sulfate was examined using immunohistochemistry. With SVT, the density of this proteoglycan increased around individual myocytes. With post-SVT, the relative distribution of chondroitin sulfate returned to control levels. Thus, SVT cardiomyopathy was associated with reduced collagen concentration and cross-linking, diminished myocyte basement membrane adhesion capacity, and increased proteoglycans. Recovery from SVT cardiomyopathy resulted in increased collagen concentration, and a normalization of myocyte adhesion capacity and proteoglycan distribution. These results suggest that changes within the ECM are a dynamic process and accompany the LV systolic and diastolic function as well as ventricular and myocyte remodeling during the progression and regression from cardiomyopathic disease.
Spinale
F G
FG
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.
Zellner
J L
JL
Johnson
W S
WS
Eble
D M
DM
Munyer
P D
PD
D000704:Analysis of Variance; D000818:Animals; D001485:Basement Membrane; D009202:Cardiomyopathies / Q000473:pathology / Q000503:physiopathology*; D002448:Cell Adhesion / Q000502:physiology; D002809:Chondroitin Sulfates / Q000378:metabolism; D003094:Collagen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000648:ultrastructure*; D006339:Heart Rate / Q000502:physiology*; D046911:Macromolecular Substances; D009210:Myofibrils / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D013552:Swine; D016277:Ventricular Function, Left / Q000502:physiology
D046911:Macromolecular Substances; D011509:Proteoglycans; D012333:RNA, Messenger; D002809:Chondroitin Sulfates; D003094:Collagen