title: Plasma levels of granzyme B are increased in patients with lipid-rich carotid plaques as determined by echogenicity.
abstract: Increased echolucency of carotid plaques is associated with an increased risk of ischemic stroke. Inflammation and apoptosis of vascular smooth muscle cells in the arterial wall are involved in the atherosclerotic process and destabilization of the plaque. Granzyme B (GrB) is a key mediator of T cell-mediated cytotoxicity, and we therefore hypothesized that this protease could distinguish echolucent from other plaques. Ultrasound-determined echolucency of atherosclerotic plaques was assessed prior to carotid endarterectomy/angioplasty in 57 consecutively recruited patients with high-grade internal carotid stenosis. Plasma levels of GrB were measured by enzyme immunoassay prior to surgery. Patients with carotid atherosclerosis had significantly higher plasma levels of GrB compared to healthy controls (n=16) (p<0.01), with particularly high levels in those with an echolucent lesion. While there were no differences in traditional cardiovascular risk factors or CRP between those with echolucent (n=16) and those with echogenic/heterogeneous (n=41) plaques, the echolucent group had markedly raised plasma levels of GrB (p<0.01). Patients with high levels of circulating granzyme B also had more ischemic lesions on cerebral MRI prior to surgery. Raised plasma levels of GrB in echolucent carotid plaques with increased frequency of cerebrovascular events suggest that GrB may be a marker of plaque instability.
authors.affiliation: Department of Neurology, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, Oslo, Norway. mona.skjelland@rikshospitalet.no
authors.forename: Mona
authors.initials: M
authors.lastname: Skjelland
authors.forename: Annika E
authors.initials: AE
authors.lastname: Michelsen
authors.forename: Kirsten
authors.initials: K
authors.lastname: Krohg-Sørensen
authors.forename: Bjørn
authors.initials: B
authors.lastname: Tennøe
authors.forename: Arve
authors.initials: A
authors.lastname: Dahl
authors.forename: Søren
authors.initials: S
authors.lastname: Bakke
authors.forename: Frank
authors.initials: F
authors.lastname: Brosstad
authors.forename: Jan K
authors.initials: JK
authors.lastname: Damås
authors.forename: David
authors.initials: D
authors.lastname: Russell
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D016893:Carotid Stenosis / Q000097:blood* / Q000145:classification / Q000000981:diagnostic imaging*; D016022:Case-Control Studies; D005260:Female; D053804:Granzymes / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018615:Ultrasonography, Doppler, Color / Q000379:methods*
chemical_list: D015415:Biomarkers; D053804:Granzymes