Expression of type V secretory phospholipase A in myocardial remodelling after infarction.
OBJECTIVE
Secretory phospholipase A2 is associated with ischaemic injury in the human heart, but the distribution of type V secretory phospholipase A2 (sPLA2-V) remains unknown. The significance of sPLA2-V in myocardial infarction was investigated histopathologically.


METHODS
Sequential changes in the localization of sPLA2-V and its mRNA in myocardial tissues obtained from 30 autopsied hearts were examined by immunohistochemistry and in situ hybridization and compared with those of fibronectin, vascular endothelial growth factor (VEGF), interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, and cyclooxygenase-2 (COX-2).


RESULTS
No expression of sPLA2-V was observed in normal heart, but it was promptly expressed in wavy myofibres positive for fibronectin just after the onset of infarction. sPLA2-V was subsequently expressed in ischaemic cardiomyocytes around the lesion. The expression decreased at the granulation tissue and disappeared at the chronic stage with scar formation. The distribution of the signal for sPLA2-V mRNA paralleled that of the protein. Ischaemic myocytes around the lesion expressed VEGF, IL-1beta, TNF-alpha and COX-2 at all stages.


CONCLUSIONS
sPLA2-V production in myocardium is limited to the acute phase of infarction. sPLA2-V may play a dual role, acting both to remove degraded cell-membrane through cooperative activity with COX-2 in necrotic areas and to attack ischaemic myocytes around the lesion via degradation of membrane phospholipids.
Ishikawa
Y
Y
Department of Pathology, School of Dentistry, Nihon University, Tokyo, Japan. yukio@med.toho-u.ac.jp
Komiyama
K
K
Masuda
S
S
Murakami
M
M
Akasaka
Y
Y
Ito
K
K
Akishima-Fukasawa
Y
Y
Kimura
M
M
Fujimoto
A
A
Kudo
I
I
Ishii
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D051546:Cyclooxygenase 2; D005260:Female; D005353:Fibronectins / Q000032:analysis; D015971:Gene Expression Regulation, Enzymologic; D054505:Group V Phospholipases A2; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000032:analysis; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D010741:Phospholipases A / Q000235:genetics* / Q000378:metabolism; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D020257:Ventricular Remodeling
D005353:Fibronectins; D007375:Interleukin-1; D008565:Membrane Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054505:Group V Phospholipases A2; C516299:PLA2G5 protein, human; D054467:Phospholipases A2