BLTR1 and CD36 Expressing Microvesicles in Atherosclerotic Patients and Healthy Individuals

Mathilde Sanden; Jaco Botha; Michael René Skjelbo Nielsen; Morten Hjuler Nielsen; Erik Berg Schmidt; Aase Handberg

doi:10.3389/fcvm.2018.00156

BLTR1 and CD36 Expressing Microvesicles in Atherosclerotic Patients and Healthy Individuals

Front Cardiovasc Med. 2018 Oct 30:5:156. doi: 10.3389/fcvm.2018.00156. eCollection 2018.

Authors

Mathilde Sanden¹, Jaco Botha^{1

2}, Michael René Skjelbo Nielsen³, Morten Hjuler Nielsen¹, Erik Berg Schmidt³, Aase Handberg^{1

2}

Affiliations

¹ Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
² Department of Clinical Medicine, Faculty of Medicine, Aalborg University, Aalborg, Denmark.
³ Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

Abstract

Aims: Monocytes/macrophages play a crucial role in the development, progression, and complication of atherosclerosis. In particular, foam cell formation driven by CD36 mediated internalization of oxLDL leads to activation of monocytes and subsequent release of microvesicles (MVs) derived from monocytes (MMVs). Further, pro-inflammatory leukotriene B4 (LTB4) derived from arachidonic acid promotes atherosclerosis through the high-affinity receptor BLTR1. Thus, we aimed to investigate the correlation between different MMV phenotypes (CD14⁺ MVs) on the one hand, and arachidonic acid and eicosapentaenoic acid contents in different compartments including atherosclerotic plaques, plasma, and granulocytes on the other. Methods and Results: Samples from patients with femoral atherosclerosis and healthy controls were analyzed on an Apogee A60 Micro-PLUS flow cytometer. Platelet-poor plasma was labeled with lactadherin-FITC, anti-CD14-APC, anti-CD36-PE, and anti-BLTR1-AF700. Eicosapentaenoic acid and arachidonic acid content in different compartments in patients were analyzed using gas chromatography. Compared to controls, patients had lower levels of BLTR1⁺ MVs (p = 0.007), CD14⁺BLTR1⁺ MVs (p = 0.007), and CD14⁺BLTR1⁺CD36⁺ MVs (p = 0.001). Further, in patients CD14⁺ MVs and CD14⁺CD36⁺ MVs correlated inversely with arachidonic acid in granulocytes (r = -0.302, p = 0.039 and r = -0.322, p = 0.028, respectively). Moreover, CD14⁺CD36⁺ MVs correlated inversely with arachidonic acid in plasma phospholipids in patients (r = -0.315, p = 0.029), and positively with triglyceride in both patients (r = 0.33, p = 0.019) and controls (r = 0.46, p = 0.022). Conclusion: This is the first study of its kind and thus the results are explorative and only indicative. BLTR1⁺ MVs and CD14⁺CD36⁺ MVs has potential as markers of atherosclerosis pathophysiology, but this needs further investigation.

Keywords: BLT1; arachidonic acid; atherosclerosis; eicosapentaenoic acid; extracellular vesicles; flow cytometry; leukotriene b4 receptor; microvesicles.