Colocalization of myocardial fibrosis and inflammatory cells in rats.
BACKGROUND
Left ventricular overload and aging lead to an increase in fibrosis in the rat cardiac interstitium. The relationship between fibrosis, fibroblast activity, and inflammatory cell infiltration, was explored in spontaneously hypertensive rats (SHR) and Wistar controls.


METHODS
The left ventricle of three groups of eight SHR and eight Wistar controls hearts were sectioned for light microscopy, immunohistochemistry, and in situ hybridization with a cDNA probe encoding the murine alpha 1 chain of type I collagen. Fibrosis was measured morphometrically. Monoclonal antibodies directed against Ia antigen, CD8+ cytotoxic, CD4+ helper lymphocytes and monocyte/macrophages were used to localize and quantify the inflammatory cells.


RESULTS
In 2-month-old rats, with nearly normal interstitial cardiac tissue, fibroblasts expressing collagen mRNA were located around coronary vessels. The areas of fibrosis and interstitial cellular infiltration were more extensive in 22-month-old rats than in 12-month-old rats and greater in SHR than in Wistar. Fibroblasts expressing collagen mRNA were mainly found at the border between fibrosis and myocytic cells, and were always colocalized with lymphocytes and macrophages. The interstitial areas of fibrosis and collagen I expressing fibroblasts had the same pattern of infiltrating cells in normotensive rats than in SHR. Fibrosis and the density of macrophages and CD4+ lymphocytes were correlated.


CONCLUSIONS
Thus, fibroblast activity could be closely related to the presence of lymphocytes and macrophages in the myocardium of spontaneously hypertensive and aged rats.
Hinglais
N
N
U28 INSERM, Paris, France.
Heudes
D
D
Nicoletti
A
A
Mandet
C
C
Laurent
M
M
Bariéty
J
J
Michel
J B
JB
D000375:Aging / Q000276:immunology / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal; D006332:Cardiomegaly / Q000276:immunology / Q000473:pathology; D003094:Collagen / Q000032:analysis; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis / Q000276:immunology / Q000473:pathology; D009206:Myocardium / Q000737:chemistry / Q000276:immunology* / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D003094:Collagen