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Article Dans Une Revue Circulation Research Année : 2024

Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes

Jean-Baptiste Julla
Bao Tran Vuong
Camille Blériot
Elena Carcarino
Joe de Keizer
Ivan Nemazanyy
Kennan Khider
Sophie Lemoine
Claire Vandiedonck
Samy Hadjadj
Fawaz Alzaid
Jean-François Gautier
Nicolas Venteclef

Résumé

BACKGROUND: Diabetes is a major risk factor for atherosclerotic cardiovascular diseases with a 2-fold higher risk of cardiovascular events in people with diabetes compared with those without. Circulating monocytes are inflammatory effector cells involved in both type 2 diabetes (T2D) and atherogenesis. METHODS: We investigated the relationship between circulating monocytes and cardiovascular risk progression in people with T2D, using phenotypic, transcriptomic, and metabolomic analyses. cardiovascular risk progression was estimated with coronary artery calcium score in a cohort of 672 people with T2D. RESULTS: Coronary artery calcium score was positively correlated with blood monocyte count and frequency of the classical monocyte subtype. Unsupervised k-means clustering based on monocyte subtype profiles revealed 3 main endotypes of people with T2D at varying risk of cardiovascular events. These observations were confirmed in a validation cohort of 279 T2D participants. The predictive association between monocyte count and major adverse cardiovascular events was validated through an independent prospective cohort of 757 patients with T2D. Integration of monocyte transcriptome analyses and plasma metabolomes showed a disruption of mitochondrial pathways (tricarboxylic acid cycle, oxidative phosphorylation pathway) that underlined a proatherogenic phenotype. CONCLUSIONS: In this study, we provide evidence that frequency and monocyte phenotypic profile are closely linked to cardiovascular risk in patients with T2D. The assessment of monocyte frequency and count is a valuable predictive marker for risk of cardiovascular events in patients with T2D. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04353869
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hal-04534577 , version 1 (02-07-2024)

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Jean-Baptiste Julla, Diane Girard, Marc Diedisheim, Pierre-Jean Saulnier, Bao Tran Vuong, et al.. Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes. Circulation Research, 2024, 134 (2), pp.189-202. ⟨10.1161/circresaha.123.322757⟩. ⟨hal-04534577⟩
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