title: Mast cells in human carotid atherosclerotic plaques are associated with intraplaque microvessel density and the occurrence of future cardiovascular events.
abstract: OBJECTIVE
  Human autopsy, animal, and cell culture studies together have merged in a concept suggesting participation of mast cells (MCs) in the generation of atherosclerotic plaques. More specifically, these studies have suggested MC-induced intraplaque neovascularization as one mechanism by which MCs may render the plaques vulnerable. The present study was designed to assess the association between MC numbers and neovascularization in human atherosclerotic plaques, and to relate the abundance of plaque MCs to the occurrence of adverse cardiovascular events during the follow-up.
  
  
  RESULTS
  Atherosclerotic plaques of 270 patients suffering from carotid artery stenosis were stained for the presence of MCs (MC tryptase). Furthermore, during a follow-up of 3 years, cardiovascular-related endpoints were assessed in 253 patients. On average a high number of MCs were observed per plaque cross-section [median 108 (55-233) cells per section]. Plaques with high MC numbers revealed an unstable lipid-rich inflammatory phenotype and were associated with symptomatic patients. In addition, MC numbers were positively associated with microvessel density (r = 0.416, P < 0.001). Patients with high intraplaque MC numbers showed significantly more cardiovascular events during the follow-up (58/142 vs. 31/111 events, P = 0.029). In a multivariate analysis with correction for the main risk factors of cardiovascular diseases, MCs remained independently associated with adverse cardiovascular events (P = 0.025).
  
  
  CONCLUSIONS
  Mast cells are highly prevalent in human carotid atherosclerotic lesions and associated with plaque microvessel density. Furthermore, intraplaque MC numbers associate with future cardiovascular events.
authors.affiliation: Experimental Cardiology Laboratory (room G02.523), University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: Willems
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
authors.forename: Ilze
authors.initials: I
authors.lastname: Bot
authors.forename: Paul H A
authors.initials: PH
authors.lastname: Quax
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: de Borst
authors.forename: Jean-Paul P M
authors.initials: JP
authors.lastname: de Vries
authors.forename: Sander M
authors.initials: SM
authors.lastname: van de Weg
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Johan
authors.initials: J
authors.lastname: Kuiper
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology / Q000473:pathology; D016893:Carotid Stenosis / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D016022:Case-Control Studies; D016894:Endarterectomy, Carotid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008407:Mast Cells / Q000201:enzymology / Q000473:pathology*; D055806:Microvessels / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D011183:Postoperative Complications / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome; D053802:Tryptases / Q000378:metabolism
chemical_list: D053802:Tryptases
keywords: Atherosclerosis; Inflammation; Intraplaque neovascularization; Mast cells; Unstable plaque