title: Soluble CD40L in peripheral artery disease. Relationship with disease severity, platelet markers and the effects of angioplasty.
abstract: Although soluble CD40L (sCD40L, possibly derived from platelets and pro-inflammatory in vitro) may be implicated in thrombosis and haemostasis, there are little data in peripheral artery disease (PAD). We hypothesised the following: (a) that sCD40L relates to the clinical severity of PAD; and (b) that peripheral artery angioplasty acutely raises sCD40L levels. sCD40L was compared to established platelet markers soluble P selectin, platelet microparticles and platelet surface expression of CD62 and CD63. We recruited 36 healthy controls, 33 patients with intermittent claudication (IC), and 33 with symptomatically more severe critical limb ischaemia (CLI), measuring plasma markers by ELISA and membrane markers by flow cytometry. Eleven patients with CLI subsequently underwent peripheral artery angioplasty: blood was taken before and 10 minutes after the intervention. Results show that sCD40L was raised in IC at median 68 (IQR 28-333) pg/ml and in CLI at 64 (34-282) pg/mL compared to 35 (IQR 28-55) pg/ml in the healthy controls (p=0.009). Levels were no different between IC and CLI. The same distribution pattern was present for soluble P selectin, %platelets CD62+ve and CD63+ve. sCD40L failed to correlate significantly with ABPI (p=0.264), unlike %platelets CD62+ve (p=0.0032) and CD63+ve (p=0.009). Pre-angioplasty sCD40L level of 72 (35-610) ng/ml rose to 100 ng/ml (IQR=60-237)(p=0.018) post-angioplasty. Plasma sCD40L, in addition to other platelet indices, is raised in peripheral atherosclerosis and is increased by peripheral artery angioplasty, although levels seem unrelated to clinical severity. Failure to correlate with other markers suggest the platelet may not be the sole source of sCD40L, and that other cells may contribute to plasma levels.
authors.affiliation: Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, Birmingham, UK. a.blann@bham.ac.uk
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Blann
authors.forename: Kiat T
authors.initials: KT
authors.lastname: Tan
authors.forename: Muzahir H
authors.initials: MH
authors.lastname: Tayebjee
authors.forename: Indran
authors.initials: I
authors.lastname: Davagnanam
authors.forename: Mark
authors.initials: M
authors.lastname: Moss
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017130:Angioplasty / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000097:blood; D007511:Ischemia / Q000097:blood; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000473:pathology; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D012720:Severity of Illness Index; D012995:Solubility
chemical_list: D015415:Biomarkers; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D023201:CD40 Ligand