Human monocyte-derived macrophages: Pathogenetic role in plaque rupture associated to systemic inflammation. (15th February 2021)

• Record Type: Journal Article
• Authors: Fracassi, Francesco; Niccoli, Giampaolo; Cosentino, Nicola; Eligini, Sonia; Fiorelli, Susanna; Fabbiocchi, Franco; Vetrugno, Vincenzo; Refaat, Hesham; Montone, Rocco Antonio; Marenzi, Giancarlo; Tremoli, Elena; Crea, Filippo
• Is Part Of: International journal of cardiology. Volume 325(2021)
• Page Start: 1
• Page End: 8
• Publication Date: 2021-02-15
• Subjects: Monocyte-derived macrophages -- Optical coherence tomography -- Plaque rupture -- Inflammation -- Coronary thrombosis -- Acute coronary syndrome; ACS acute coronary syndromes -- CAD coronary artery disease -- CRP C-reactive protein -- IFC intact fibrous cap -- MDMs human monocyte-derived macrophages -- MMP-9 matrix metalloproteinase-9 -- OCT optical coherence tomography -- TCFA thin cap fibroatheroma -- TF tissue factor -- TG-2 transglutaminase-2; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2020.09.071
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: 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/Ll): 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 (15.2%) to Group 2 and 24 (36.4%) to Group 3. The "round" MDMs were significantly more frequent in Group 1 (39.25 ± 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 efferocytosis (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. Highlights: Monocyte-derived macrophages to study macrophages infiltrating coronary plaques. Optical Coherence Tomography to identify the mechanism of plaque destabilization. Pro-thrombotic, oxidative macrophages are prevalent in ruptures with inflammation.