Increased expression of fibronectin isoforms after myocardial infarction in rats.
Fibronectin is a known chemoattractant for several cell types which play a role in the wound healing process, like fibroblasts, endothelial cells and macrophages. In addition, fibronectin generates a scaffold to which other extracellular matrix components can attach. The possible involvement of fibronectin in the wound healing process after myocardial infarction (MI) was investigated by studying the expression of fibronectin isoforms after induction of a MI in the rat. Deposition of plasma (pFN) and cellular fibronectin (cFN) protein was determined immunohistochemically, using monoclonal antibodies specific for cFN and polyclonal anti-human total FN (tFN antibodies). Expression of the mRNAs of total cFN and the embryonic isoforms EIIIA and EIIIB was investigated, using in situ hybridization (ISH). The ratio between EIIIA containing fibronectin (EIIIA+-FN) mRNA and total cFN mRNA was determined using a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). cFN protein was present from day 4 until day 35 after infarction and was located around the area of infarction, in the epi- and endomyocardium and in the wall of larger vessels. pFN was found in the infarcted cardiomyocytes 1 day after the induction of the MI. From day 4 on pFN protein deposition was found in the border zone of the infarction and in the wall of larger vessels. pFN immunoreactivity remained present at high levels around the area of infarction and in the vessel wall throughout the entire period of investigation (90 days). From day 35 after the infarction pFN protein was detected in cardiomyocytes of the right ventricle and septum. cFN mRNA, determined by in situ hybridization, was present in the border zone of the infarcted area as early as 1 day after MI, and its expression peaked at 4 days after MI. Four days after MI the mRNA's coding for both the embryonic isoforms EIIIA and EIIIB could also be detected in the same area. Because expression of the EIIIA isoform was more abundant than the EIIIB isoform we only determined the percentage of the EIIIIA containing isoform from total FN. EIIIA+ mRNA was elevated 1 day after MI. We conclude that various fibronectin isoforms including the embryonic isoforms accumulate in the heart after MI. This suggests that these isoforms may play a role in the wound healing process in the left ventricle of the infarcted heart.
Ulrich
M M
MM
Cardiovascular Research Institute Maastricht, Department of Pathology, Universiteit Maastricht, Maastricht, The Netherlands.
Janssen
A M
AM
Daemen
M J
MJ
Rappaport
L
L
Samuel
J L
JL
Contard
F
F
Smits
J F
JF
Cleutjens
J P
JP
D000818:Animals; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D007536:Isomerism; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005353:Fibronectins; D012333:RNA, Messenger