Carotid plaque instability and ischemic symptoms are linked to immaturity of microvessels within plaques.
BACKGROUND
Instability and rupture of carotid atherosclerotic plaques leads to thromboemboli and ischemic symptoms. Angiogenesis occurs within atherosclerotic plaques, and plaque vulnerability and symptomatic carotid disease have been associated with increased numbers of microvessels. In addition to microvessel number, it is possible that the phenotypes of intraplaque vessels could influence plaque stability. To test this, the morphology and maturity of vessels within plaques from symptomatic and asymptomatic patients was determined.


METHODS
Carotid plaques were collected after endarterectomy from a cohort of 13 asymptomatic patients and 30 symptomatic patients. Plaques were sectioned and immunostained for the presence of endothelial cells, vascular smooth muscle cells, macrophages, and vascular endothelial growth factor. Sections were assessed for microvessel morphology, maturity as judged by smooth muscle cell cover, and the presence of vascular endothelial growth factor and macrophages.


RESULTS
Two types of vascular structure were observed within plaques, microvessels and dilated, highly irregular multilobular vessels. These irregular dysmorphic vessels were found almost exclusively in plaques from symptomatic patients. The dysmorphic vessels lacked smooth muscle cells and were highly immature. Plaques also contained vascular endothelial growth factor, and this was observed adjacent to the dysmorphic vessels. This growth factor was found colocalized with macrophages.


CONCLUSIONS
Symptomatic carotid plaques contain abnormal, immature microvessels similar to those found in tumors and healing wounds. Such vessels could contribute to plaque instability by acting as sites of vascular leakage by inflammatory cell recruitment. The immature vessels within plaques may be therapeutic targets for promoting plaque stabilization.
Dunmore
Benjamin J
BJ
Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK.
McCarthy
Mark J
MJ
Naylor
A Ross
AR
Brindle
Nicholas P J
NP
D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000150:complications* / Q000378:metabolism / Q000601:surgery; D002545:Brain Ischemia / Q000209:etiology* / Q000517:prevention & control; D002340:Carotid Artery Diseases / Q000150:complications* / Q000378:metabolism / Q000601:surgery; D018450:Disease Progression; D016894:Endarterectomy, Carotid; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D020767:Intracranial Thrombosis / Q000150:complications* / Q000517:prevention & control; D008264:Macrophages / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A