Dynamin and perforin are associated with neovascularisation in advanced carotid plaques.
Intimal plaque neovascularization is associated with the development of symptomatic disease and thrombosis, with new 'leaky' fragile microvessels prone to haemorrhage. Perforin or pore forming protein is involved in vascular cell death by forming pores in target cells. Enzymes, in particular, granzyme B are secreted by immune infiltrates present in inflammatory plaque regions and have been shown to induce endothelial cell apoptosis. Similarly, dynamin-2 is a GTPase which mediates oxidised low density lipoprotein-induced apoptosis and is also required for granzyme B-mediated exocytosis and apoptosis. Our pilot studies identified increased expression of these proteins in complicated atherosclerotic plaques. Here we demonstrate by immunohistochemistry that both proteins are over-expressed in angiogenic regions of complicated carotid plaques. Dynamin-2 was extensively localised around microvessels and in immune infiltrating cells whilst perforin was localised in immune infiltrating cells, endothelial cells and smooth muscle cells. Over-expression of these proteins may contribute to plaque destabilisation by increasing cellular apoptosis in vulnerable atherosclerotic plaques.
ICCC, St Pau Hospital, Barcelona, Spain. m.a.slevin@mmu.ac.uk
Mark
M
Slevin
Priya
P
Ethirajan
Mohammed
M
Molki
John
J
Gaffney
Shant
S
Kumar
Pat
P
Kumar
Jerzy
J
Krupinski
D002340:Carotid Artery Diseases / Q000473:pathology* / Q000503:physiopathology* / Q000601:surgery; D016893:Carotid Stenosis / Q000473:pathology* / Q000503:physiopathology*; D034285:Dynamin II / Q000235:genetics / Q000378:metabolism*; D016894:Endarterectomy, Carotid; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D054353:Perforin / Q000235:genetics / Q000378:metabolism*; D012422:Rupture, Spontaneous / Q000209:etiology; D013927:Thrombosis / Q000209:etiology
D054353:Perforin; D034285:Dynamin II