Bone marrow endothelial dysfunction promotes myeloid cell expansion in cardiovascular disease

Rohde, David; Vandoorne, Katrien; Lee, I-Hsiu; Grune, Jana; Zhang, Shuang; McAlpine, Cameron S.; Schloss, Maximilian J.; Nayar, Ribhu; Courties, Gabriel; Frodermann, Vanessa; Wojtkiewicz, Gregory R.; Honold, Lisa; Chen, Qi; Schmidt, Stephen; Iwamoto, Yoshiko; Sun, Yuan; Cremer, Sebastian; Hoyer, Friedrich Felix; Iborra‐Egea, Oriol; Muñoz-Guijosa, Christian; Ji, Fei; Zhou, Bin; Adams, Ralf H.; Wythe, Joshua D.; Hidalgo, Juan; Watanabe, Hideto; Jung, Yookyung; Laan, A.M. van der; Piek, Jan J.; Kfoury, Youmna; Désogère, Pauline; Vinegoni, Claudio; Dutta, Partha; Sadreyev, Ruslan I.; Caravan, Peter; Bayés‐Genís, Antoni; Libby, Peter; Scadden, David T.; Lin, Charles P.; Naxerova, Kamila; Świrski, Filip K.; Nahrendorf, Matthias

doi:10.1038/s44161-021-00002-8

Cited by 48 publications

(32 citation statements)

References 97 publications

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“…The increased uptake has also been found in the bone marrow and spleen of patients with CAD compared with those without. This confirms the association between bone marrow and spleen hematopoietic activation and an increase in the proinflammatory mediators involved in atherosclerotic plaque inflammation [ 71 , 72 , 73 ].…”

Section: Introductionsupporting

confidence: 82%

“…Bone marrow vasculature undergoes the same stimuli as other tissues. Thus, inflammation-induced endothelial dysfunction involves the bone marrow arteries inducing HSCs proliferation and the increased release of leukocytes into the circulation [ 73 , 186 , 196 ]. Once recruited by the activated endothelial cells, these leukocytes release cytokines and proteases, and migrate to the arterial wall, further promoting inflammation [ 197 , 198 ].…”

Section: Introductionmentioning

confidence: 99%

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The Role of Inflammation in Cardiovascular Disease

Henein

Vancheri

Longo³

et al. 2022

IJMS

233

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Atherosclerosis is a chronic inflammatory disease, in which the immune system has a prominent role in its development and progression. Inflammation-induced endothelial dysfunction results in an increased permeability to lipoproteins and their subendothelial accumulation, leukocyte recruitment, and platelets activation. Recruited monocytes differentiate into macrophages which develop pro- or anti-inflammatory properties according to their microenvironment. Atheroma progression or healing is determined by the balance between these functional phenotypes. Macrophages and smooth muscle cells secrete inflammatory cytokines including interleukins IL-1β, IL-12, and IL-6. Within the arterial wall, low-density lipoprotein cholesterol undergoes an oxidation. Additionally, triglyceride-rich lipoproteins and remnant lipoproteins exert pro-inflammatory effects. Macrophages catabolize the oxidized lipoproteins and coalesce into a lipid-rich necrotic core, encapsulated by a collagen fibrous cap, leading to the formation of fibro-atheroma. In the conditions of chronic inflammation, macrophages exert a catabolic effect on the fibrous cap, resulting in a thin-cap fibro-atheroma which makes the plaque vulnerable. However, their morphology may change over time, shifting from high-risk lesions to more stable calcified plaques. In addition to conventional cardiovascular risk factors, an exposure to acute and chronic psychological stress may increase the risk of cardiovascular disease through inflammation mediated by an increased sympathetic output which results in the release of inflammatory cytokines. Inflammation is also the link between ageing and cardiovascular disease through increased clones of leukocytes in peripheral blood. Anti-inflammatory interventions specifically blocking the cytokine pathways reduce the risk of myocardial infarction and stroke, although they increase the risk of infections.

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Section: Introductionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

The Role of Inflammation in Cardiovascular Disease

Henein

Vancheri

Longo³

et al. 2022

IJMS

233

View full text Add to dashboard Cite

show abstract

“…106 Mouse meninges have been shown to contain a pool of monocytes and neutrophils derived from the adjacent skull and vertebral BMs with a specific transcriptional signature distinct from cells derived from the peripheral blood, 107 as well as a lymphopoietic niche hosting B cells. 108 Emerging evidence shows that various cardiovascular diseases promote an alteration of the BM niche that causes an overproduction of proinflammatory myeloid subsets and systemic leukocytosis, 109 suggesting that the presence of cardiovascular risk factors may induce vascular BM remodeling with deleterious impact on subsequent strokes. In particular, in the skull, recent data demonstrate that the BM niches are different from those in other bones and house a highly heterogeneous set of immune cells displaying unique transcriptional signatures, which are also manifested in specific disease-associated patterns in the human skull, including in patients with stroke.…”

Section: Source and Mobilization Of Immune Myeloid Cells In Strokementioning

confidence: 99%

Immune Pathways in Etiology, Acute Phase, and Chronic Sequelae of Ischemic Stroke

Endres

Moro

Nolte

et al. 2022

Circulation Research

149

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Inflammation and immune mechanisms are crucially involved in the pathophysiology of the development, acute damage cascades, and chronic course after ischemic stroke. Atherosclerosis is an inflammatory disease, and, in addition to classical risk factors, maladaptive immune mechanisms lead to an increased risk of stroke. Accordingly, individuals with signs of inflammation or corresponding biomarkers have an increased risk of stroke. Anti-inflammatory drugs, such as IL (interleukin)-1β blockers, methotrexate, or colchicine, represent attractive treatment strategies to prevent vascular events and stroke. Lately, the COVID-19 pandemic shows a clear association between SARS-CoV2 infections and increased risk of cerebrovascular events. Furthermore, mechanisms of both innate and adaptive immune systems influence cerebral damage cascades after ischemic stroke. Neutrophils, monocytes, and microglia, as well as T and B lymphocytes each play complex interdependent roles that synergize to remove dead tissue but also can cause bystander injury to intact brain cells and generate maladaptive chronic inflammation. Chronic systemic inflammation and comorbid infections may unfavorably influence both outcome after stroke and recurrence risk for further stroke. In addition, stroke triggers specific immune depression, which in turn can promote infections. Recent research is now increasingly addressing the question of the extent to which immune mechanisms may influence long-term outcome after stroke and, in particular, cause specific complications such as poststroke dementia or even poststroke depression.

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“…26,50 VEGF-A and VEGFR2 signaling facilitate curbing of myocardial infarction induced emergency hematopoiesis. 51,52 VEGF-C is reported to protect integrity of BM niche and improve recovery after irradiation-induced injury. 53 Hence, VEGF signaling actively participate in hematopoiesis under steady-state and disease-related disturbed hematopoietic condition.…”

Section: Discussionmentioning

confidence: 99%

Antipsychotic drugs induce vascular defects in hematopoietic organs

et al. 2022

Self Cite

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Antipsychotic agents are clinically utilized to treat schizophrenia and other mental disorders. These drugs induce neurological and metabolic side effects, but their influence on blood vessels remains largely unknown. Here, we show that haloperidol, one of the most frequently prescribed antipsychotic agents, induces vascular defects in bone marrow. Acute haloperidol treatment results in vascular dilation that is specific to hematopoietic organs. This vessel dilation is associated with disruption of hematopoiesis and hematopoietic stem/progenitor cells (HSPCs), both of which are reversible after haloperidol withdrawal. Mechanistically, haloperidol treatment blocked the secretion of vascular endothelial growth factor A (VEGF‐A) from HSPCs. Genetic blockade of VEGF‐A secretion from hematopoietic cells or inhibition of VEGFR2 in endothelial cells result in similar vessel dilation in bone marrow during regeneration after irradiation and transplantation. Conversely, VEGF‐A gain of function rescues the bone marrow vascular defects induced by haloperidol treatment and irradiation. Our work reveals an unknown effect of antipsychotic agents on the vasculature and hematopoiesis with potential implications for drug application in clinic.

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Bone marrow endothelial dysfunction promotes myeloid cell expansion in cardiovascular disease

Cited by 48 publications

References 97 publications

The Role of Inflammation in Cardiovascular Disease

The Role of Inflammation in Cardiovascular Disease

Immune Pathways in Etiology, Acute Phase, and Chronic Sequelae of Ischemic Stroke

Antipsychotic drugs induce vascular defects in hematopoietic organs

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