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Limited proliferation capacity of aortic intima resident macrophages requires monocyte recruitment for atherosclerotic plaque progression.

ABSTRACT: Early atherosclerosis depends upon responses by immune cells resident in the intimal aortic wall. Specifically, the healthy intima is thought to be populated by vascular dendritic cells (DCs) that, during hypercholesterolemia, initiate atherosclerosis by being the first to accumulate cholesterol. Whether these cells remain key players in later stages of disease is unknown. Using murine lineage-tracing models and gene expression profiling, we reveal that myeloid cells present in the intima of the aortic arch are not DCs but instead specialized aortic intima resident macrophages (Mac^AIR) that depend upon colony-stimulating factor 1 and are sustained by local proliferation. Although Mac^AIR comprise the earliest foam cells in plaques, their proliferation during plaque progression is limited. After months of hypercholesterolemia, their presence in plaques is overtaken by recruited monocytes, which induce Mac^AIR-defining genes. These data redefine the lineage of intimal phagocytes and suggest that proliferation is insufficient to sustain generations of macrophages during plaque progression.

SUBMITTER: Williams JW

PROVIDER: S-EPMC7502558 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Limited proliferation capacity of aortic intima resident macrophages requires monocyte recruitment for atherosclerotic plaque progression.

Williams Jesse W JW Zaitsev Konstantin K Kim Ki-Wook KW Ivanov Stoyan S Saunders Brian T BT Schrank Patricia R PR Kim Kyeongdae K Elvington Andrew A Kim Seung Hyeon SH Tucker Christopher G CG Wohltmann Mary M Fife Brian T BT Epelman Slava S Artyomov Maxim N MN Lavine Kory J KJ Zinselmeyer Bernd H BH Choi Jae-Hoon JH Randolph Gwendalyn J GJ

Nature immunology 20200907 10

Early atherosclerosis depends upon responses by immune cells resident in the intimal aortic wall. Specifically, the healthy intima is thought to be populated by vascular dendritic cells (DCs) that, during hypercholesterolemia, initiate atherosclerosis by being the first to accumulate cholesterol. Whether these cells remain key players in later stages of disease is unknown. Using murine lineage-tracing models and gene expression profiling, we reveal that myeloid cells present in the intima of the ...[more]

PMID: 32895539

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Project description:Background and purposeGadolinium enhancement on high-resolution vessel wall imaging (HR-VWI) is an imaging marker of intracranial atherosclerotic stenosis (ICAS) plaque instability. This study aimed to evaluate the relationships between hematological inflammatory indicators and the enhancement of ICAS plaques and to search for hematological indicators that can predict ICAS plaque instability.MethodsConsecutive adult patients diagnosed with ICAS from April 2018 to December 2021 were recruited retrospectively, and every patient underwent HR-VWI. Plaque enhancement was measured qualitatively and quantitatively. The plaque-to-pituitary stalk contrast ratio (CR) indicated the degree of plaque enhancement. Clinical and laboratory data, including the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII), were recorded. The hematological inflammatory indicators were compared between ICAS patients with and without plaque enhancement and between patients with and without symptomatic plaque. The hematological inflammatory indicators and the CR were compared using linear regression. Furthermore, receiver operating characteristic curve analysis was performed to assess the discriminative abilities of the inflammatory indicators to predict plaque instability.ResultsFifty-nine patients were included. The NLR, SII and LMR were significantly correlated with plaque enhancement. The LMR was independently associated with plaque enhancement, and a linear negative correlation was observed between the LMR and CR (R = 0.716, P < 0.001). The NLR, LMR, plaque enhancement and CR were significantly associated with symptomatic ICAS, and the LMR and plaque enhancement were independent risk factors for symptomatic ICAS. The optimal cutoff value of the admission LMR to distinguish symptomatic plaque from asymptomatic plaque was 4.0 (80.0% sensitivity and 70.6% specificity).ConclusionThe LMR was independently associated with ICAS plaque enhancement and showed a linear negative correlation with CR. The LMR and plaque enhancement were independent risk factors for symptomatic ICAS. An LMR ≤ 4.0 may predict ICAS plaque instability.

Dataset Information

Limited proliferation capacity of aortic intima resident macrophages requires monocyte recruitment for atherosclerotic plaque progression.

Publications

Limited proliferation capacity of aortic intima resident macrophages requires monocyte recruitment for atherosclerotic plaque progression.

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