Regulation of Fibrillar Collagen Types I and III and Basement Membrane Type IV Collagen Gene Expression in Pressure Overloaded Rat Myocardium
Left ventricular hypertrophy is based on cardiac myocyte growth. The hypertrophic process can be considered heterogeneous based on whether it also includes a remodeling and accumulation of fibrillar types I and III collagens that are responsible for impaired myocardial stiffness. In the heart, the m...
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Published in | Circulation research Vol. 67; no. 4; pp. 787 - 794 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Hagerstown, MD
American Heart Association, Inc
01.10.1990
Lippincott |
Subjects | |
Online Access | Get full text |
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Summary: | Left ventricular hypertrophy is based on cardiac myocyte growth. The hypertrophic process can be considered heterogeneous based on whether it also includes a remodeling and accumulation of fibrillar types I and III collagens that are responsible for impaired myocardial stiffness. In the heart, the messenger RNA (mRNA) for fibrillar collagen types I and III has been detected only in cardiac fibroblasts, whereas mRNA for basement membrane collagen type IV is present in both fibroblasts and myocytes. We studied the early and long-term expression of these collagenous proteins in rat myocardium after abdominal aortic banding with renal ischemia. Complementary DNA probes for rat pro-α2(I), mouse type III and mouse type IV collagens, and chicken β-actin were used. Northern and dot blot analysis on total RNA extracted from left ventricular tissue indicated a sixfold increase in steady-state levels of mRNA for collagen type I on day 3 of abdominal aortic banding, which had declined to control levels by day 7 where it remained rather constant at 4 and 8 weeks. Type III collagen showed a similar pattern of gene expression after banding. mRNA levels for type IV collagen, on the other hand, were elevated on day 1 after banding, returning to control at day 7 and remaining constant. Actin mRNA levels also increased on day 1 of banding, followed by a rapid return to control levels. Monospecific antibody to types I and Ill collagens and immunofluorescent light microscopy on frozen sections of the myocardium revealed that at 1 week after banding, the distribution and density of these collagens were similar to those of control animals. At 8 weeks, the density of collagen type I fibers was greater than controls, and a perivascular fibrosis involving intramyocardial coronary arteries also was present. The distribution and density of collagen types III and IV, however, remained unchanged at these intervals. Thus, fibrillar collagen gene regulation and subsequent myocardial fibrosis are integral components of renovascular hypertension. The cellular origins of the fibrillar and nonfibrillar collagen mRNAs and their temporally disparate regulation suggest that separate regulatory mechanisms, involving myocytes and fibroblasts, may be responsible for the remodeling of the myocardium. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0009-7330 1524-4571 |
DOI: | 10.1161/01.res.67.4.787 |