Multi-organ dysfunction and cardiovascular pathology in metabolic diseases

Atherosclerosis, and its complications such as myocardial infarction, represent the leading cause of death worldwide. These cardiovascular diseases are part of a group of cardiometabolic disorders encompassing obesity, hypertension, liver and renal diseases, and diabetes mellitus. While atherosclerosis and myocardial infarction locally affect arteries and the heart, they represent the endpoints of organism-wide processes controlling metabolic homeostasis, blood pressure, and immune homeostasis, thus representing multi-organ diseases.

Our research group led by Clément Cochain, an expert in employing single-cell assays to characterize inflammatory cell states in cardiovascular diseases, investigates innate immune cells as essential actors in multi-organ disease in atherosclerosis, myocardial infarction and cardiometabolic disorders. We apply state-of-the art techniques of single-cell profiling and spatial gene expression analysis in experimental models of cardiometabolic diseases, to better understand the cellular and molecular mechanisms underlying innate immune cells contribution to atherosclerosis and to tissue remodeling after myocardial infarction.

Recent Results

Characterization and functional investigations of immune cells in vascular diseases: following pioneering work establishing the first single-cell level mapping of the arterial immune landscape in experimental atherosclerosis (Cochain, Circ Res 2018; Winkels, Circ Res 2018), C. Cochain more recently led an integrated single-cell RNA-seq analysis work establishing a classification of mononuclear phagocytes in experimental atherosclerosis, and revealing conservation of the main atherosclerosis-associated macrophage states from mouse to human, including TREM2 expressing foamy macrophages (Zernecke, Cardiovasc Res 2023). In a subsequent collaborative work, we demonstrated the protective role of TREM2 in atherosclerosis, via the control of key macrophage functions such as survival, efferocytosis and lipid handling (Piollet & Porsch, Nature Cardiovascular Research 2024). Recently, our team provided scRNA-seq expertise in numerous international collaborations aiming at investigating vascular immune cells in atherosclerosis (Benhmammouch, Nat Metab 2025; Lavillegrand, Nature 2024) or other vascular diseases (Quelquejay, Circ Res 2024; Al-Rifai, Nat Commun 2022).

Innate immune cells in myocardial diseases: in the past years, our team leveraged the emergence of new technologies allowing to precisely profile single immune cells by simultaneously measuring their transcriptome and their surface marker profile, to refine our understanding of immune dynamics in the heart after myocardial infarction. Notably, we evidenced the time-dependent appearance of a hitherto unknown subset of cardiac SiglecF+ neutrophils with specific functional properties in experimental myocardial infarction (Vafadarnejad, Circ Res. 2020). In further work, we precisely characterized the dynamics of monocyte-to-macrophage differentiation in the infarcted myocardium, defining a subset of TREM2-expressing monocyte-derived macrophages observed in mouse and human myocardial infarction (Rizzo, Cardiovasc Res. 2023). In recent work co-led by C. Cochain, we have furthermore investigated the interaction between platelets and macrophages as a driver of macrophage inflammatory activation (Rizakou, J Leukoc Biol 2025), and the targeting of thrombo-inflammatory pathways as a potential immune modulatory strategy after acute myocardial infarction (Rizakou, biorxiv 2025). Our team has furthermore contributed scRNA-seq expertise in various collaborations focusing on pathogenic inflammatory processes in other myocardial diseases e.g. non-ischemic heart failure (Delacroix, Biochem Pharmacol 2025) or Duchenne myopathy (Gladow, biorxiv 2025).

Projects

Axis 1: decipher cross-organ determinants of monocyte/macrophage functional heterogeneity in cardiometabolic diseases: Following up on our previous work, several active projects of our team aim to characterize cross-organ myeloid cell functional states using single-cell and spatial transcriptomics. In a project funded by the Fondation de France, we are interested in characterizing multi-organ monocyte/macrophage responses during obesity-aggravated atherosclerosis. In the ANR-funded CARDIM project, together with X. Loyer at the PARCC, we are investigating how inter-organ communication between the heart and the spleen via extracellular vesicles shapes splenic monocyte responses after myocardial infarction.

Axis 2: mechanisms of macrophage pro- and anti-fibrotic activities in heart failure: We are investigating how macrophages modulate fibrosis in the diseased heart, focusing on their dialogue with fibroblasts. To this end, we are employing state-of-the-art single-cell and spatial transcriptomics methods to study cardiac fibrotic niches. In the ANR-funded project IMOTEP, together with JS Silvestre, we are specifically focusing on how a key function of macrophages, efferocytosis, affects the pro- or anti-fibrotic activities of specific cardiac macrophage subsets.

Axis 3: neutrophil functional heterogeneity in myocardial infarction: we are investigating the functional heterogeneity of neutrophils, and the role of diverse cardiac neutrophil subsets, in cardiac repair after myocardial infarction, aiming to decipher the precise molecular mechanisms by which neutrophils can promote cardiac healing or, in contrast, have deleterious effects in the diseased heart. This work is led by M. Piollet, a postdoctoral researcher in the team supported by funding from the FRM and the Université Paris Cité IdEx – inIdEx consortium CITY.