Human monocyte-derived macrophages: Pathogenetic role in plaque rupture associated to systemic inflammation

Background: Macrophages play a key role in coronary plaque destabilization. In-vitro human monocyte-derived macrophages (MDMs) are used to study macrophages infiltrating tissue. Optical coherence tomography (OCT) provides an in-vivo insight of the coronary arteries. We compared the MDMs morpho-phenotype and culprit plaque features at OCT in acute coronary syndrome (ACS) patients according to the underlying plaque pathobiology. Methods: Sixty-six patients undergoing coronary angiography and pre-angioplasty OCT of the culprit vessel were allocated to three groups according to mechanism of ACS at OCT and C-reactive protein levels (cut-off: 2 mg/LI): 1) plaque rupture with systemic inflammation; 2) plaque rupture without systemic inflammation, 3) plaque with intact fibrous cap. A blood sample was collected to obtain MDMs, categorized as having round or spindle morphology. Results: Thirty-two patients (48.5%) were assigned to Group 1, 10 (152%) to Group 2 and 24 (36.4%) to Group 3. The round MDMs were significantly more frequent in Group 1(3925 +/- 4.98%) than in Group 2 (23.89 +/- 3.10%) and Group 3 (23.02 +/- 7.89%), p 0.008. MDMs in Group 1 as compared to Groups 2 and 3 showed lower efferocylosis (8.74 +/- 1.38 vs 9.74 +/- 2.15 vs 11.41 +/- 2.41; p 0.012), higher tissue factor levels (369.84 +/- 101.13 vs 301.89 +/- 59.78 vs 231.74 +/- 111.47; p = 0.001) and higher heme oxygenase-1 expression (678.78 -+/- 145.43 vs 419.12 +/- 74.44 vs 409.78 +/- 64.33; p 0.008). Conclusions: MDMs of ACS patients show morpho-phenotypic heterogeneity with prevalence of pro-thrombotic and pro-oxidative properties in case of plaque rupture and systemic inflammation. Such MDMs subpopulation may take part to the cellular pathways leading to fibrous cap rupture with the subsequent thrombus formation. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

The study revealed morpho-phenotypic heterogeneity of monocyte-derived macrophages (MDMs) in acute coronary syndrome (ACS) patients, with a prevalence of pro-thrombotic and pro-oxidative properties in case of plaque rupture and systemic inflammation.