Journal
THROMBOSIS AND HAEMOSTASIS
Volume 111, Issue 1, Pages 111-121Publisher
GEORG THIEME VERLAG KG
DOI: 10.1160/TH13-07-0612
Keywords
Atherosclerosis; circulating microparticles; endothelial dysfunction; hypercholesterolaemia; inflammation
Categories
Funding
- CNIC Foundation [CNIC-082008]
- ISCIII [TERCEL]
- SAFE-T project [IMI-JU] [115003]
- Spanish Ministry of Science [PNS SAF2010-16549]
- Spanish Ministry of Health [FIS PI1001115]
- FIC-Fundacion Jesus Serra
- Spanish Health Ministry (ISCIII) [PFIS-FI09/00092]
Ask authors/readers for more resources
Circulating microparticles (cMPs) seem to play important roles in vascular function. Beyond markers of activated cells, cMPs may have potential paracrine functions and influence atherosclerosis. Here, our objective was to characterise a) the abundance and phenotype of cMPs in stable statin-treated heterozygous familial hypercholesterolaemia (FH) patients exposed to life-long hypercholesterolaemia and b) the principal phenotype associated to lipid-rich atherosclerotic plaques in hFH-patients with significant atherosclerotic plaque burden. An age/gender/treatment-matched group of adult-onset non-PH hypercholesterolaemic patients (n=37/group) was comparatively analysed. cMPs were characterised by flow cytometry using annexin-V and cell surface-specific antibodies. Our study shows that LLT-FH patients had higher overall cMP-numbers (p<0.005) than LLT-non-FH patients. Endothelial cell-shed cMPs were also significantly higher in FH (p<0.0005). Within the leukocyte-derived cMP-subpopulations, FH-patients had significantly higher lymphocyte- and monocyte-derived cMP-numbers as well as cMPs carrying leukocyte-activation markers. Normalisation of cMPs by LDL levels did not affect cMP number or phenotype, indicating that the proinflammatory effect was derived from chronic vascular damage. Levels of AV(+)-total, CD45(+)-pan-leukocyte and CD45(+)/CD3(+)-lymphocyte-derived cMPs were significantly higher in FH-patients with subclinical lipid-rich atherosclerotic plaques than fibrous plaques. Levels of CD45(+)/CD3(+)-lymphocyte-MPs above 20,000/ml could differentiate between FH-patients with lipidic or non-lipidic plaques (area under the ROC curve of 0.803, 95%CI: 0.641-0.965, p=0.008). In summary, in this snapshot cross-sectional study cMP concentration and phenotype in FH differed markedly from non-FH hypercholesterolaemia. Patients with life-long high LDL exposure have higher endothelial activation and higher proinflammatory profile, even under current state-of-the-art LLT. cMPs carrying lymphocyte-epitopes appear as markers of lipid-rich atherosclerotic plaques in FH.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available