Circulating CD45+/CD3+ lymphocyte-derived microparticles map lipid-rich atherosclerotic plaques in familial hypercholesterolaemia patients

Rosa Suades; Teresa Padró; Rodrigo Alonso; José López-Miranda; Pedro Mata; Lina Badimon

doi:10.1160/TH13-07-0612

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 111(01): 111-121
DOI: 10.1160/TH13-07-0612

Platelets and Blood Cells

Schattauer GmbH

Circulating CD45⁺/CD3⁺ lymphocyte-derived microparticles map lipid-rich atherosclerotic plaques in familial hypercholesterolaemia patients

Rosa Suades

¹Cardiovascular Research Center (CSIC-ICCC), IIB-Sant Pau, Barcelona, Spain;

,

Teresa Padró

¹Cardiovascular Research Center (CSIC-ICCC), IIB-Sant Pau, Barcelona, Spain;

,

Rodrigo Alonso

²Foundation Jimenez Diaz, Madrid, Spain;

,

José López-Miranda

³Unidad de Lípidos y Arteriosclerosis, IMIBIC, Hospital Universitario Reina Sofia, Universidad de Córdoba, and CIBEROBN Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Spain;

,

Pedro Mata

²Foundation Jimenez Diaz, Madrid, Spain;

,

Lina Badimon

¹Cardiovascular Research Center (CSIC-ICCC), IIB-Sant Pau, Barcelona, Spain;

⁴Cardiovascular Research Chair, UAB, Barcelona, Spain

› Author Affiliations

Abstract

Summary

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 hFHpatients with significant atherosclerotic plaque burden. An age/gender/ treatment-matched group of adult-onset non-FH 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 cellshed 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.

Keywords

Atherosclerosis - circulating microparticles - endothelial dysfunction - hypercholesterolaemia - inflammation

Full Text

References

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