Abstract 13525: Influence of Inflammatory Cells on Local Collagen Production, Collagen Pattern and Cardiac Remodeling after Myocardial Infarction
Purpose: Despite the considerable progress in treatment strategies the acute myocardial infarction is still a major cause of mortality in the developed countries. Our hypothesis is that leukocyte infiltration can decisively influence the extracellular matrix, the amount of deposited collagen and in particular the composition of the different collagen types in infarcted areas leading to differences in the stability of the scar. This study aimed to reveal for the first time the characteristic and distribution of all known collagen subtypes in infarcted myocardial areas and to reveal the influence of inflammatory cell types on the variety of collagen patterns and myocardial function.
Methods and results: In the first instance we cultivated mouse myofibroblasts “in vitro” under normoxic and hypoxic conditions with and without different inflammatory cell types to determine the differential production of all known collagen types. Afterwards we conducted “in vivo” myocardial infarctions in CCR1-/-, CCR2-/-, CCR5-/- and CX3CR1-/- knock-out mice to “deplete” different inflammatory cell types, reveal the effect on the resulting collagen pattern and the effect on myocardial function determined by echocardiography. The “in vitro” results determined under normoxic conditions mainly a production of collagen type I, IV, VI, XII, XIV and XVIII. Co-incubation with mononuclear cells notably reduced the amount of collagen IV and VI. “In vivo” the collagen pattern changed significantly due to different points in time after myocardial infarctions (4 days to 4 weeks) and due to different knock out mice, interestingly correlating with significant differences in myocardial function. In particular the CX3CR1-/- mice showed significantly elevated amounts of collagen III, VIII, XII and XIV, the CCR2-/- mice significantly elevated amounts of collagen XIII.
Conclusions: “In vitro” and “in vivo” experiments determined that inflammatory cells have significant influence on the shape of the collagen pattern and a significant influence on myocardial function. To look ahead, a manipulation of the migration processes of inflammatory cell types after myocardial infarction could be of therapeutical value by influencing the collagen pattern in the infarcted areas.
- © 2013 by American Heart Association, Inc.