MerTK receptor cleavage promotes plaque necrosis and defective resolution in atherosclerosis

Cai, Bolin; Thorp, Edward B.; Doran, Amanda C.; Sansbury, Brian E.; Daemen, Mat J.A.P.; Dorweiler, Bernhard; Spite, Matthew; Fredman, Gabrielle; Tabas, Ira

doi:10.1172/jci90520

Cited by 171 publications

(202 citation statements)

References 39 publications

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“…Further, macrophages transduced with CA-CaMKII showed a decrease in efferocytosis ( Figure 7E). These data, together with both the lesional data presented earlier and the previously published studies on the role of MerTK in advanced plaques (9,10,27), support the concept that activation of CaMKIIγ in lesional macrophages, by suppressing an ATF6-LXRα-MerTK module, contributes to defective efferocytosis and plaque necrosis in advanced atherosclerotic lesions. Figure 6.…”

Section: Discussionsupporting

confidence: 85%

“…We found no differences in the expression of β 5 integrin, CD36, CD61, CD206, CD300F, or Tim4. CaMKII-KO macrophages did, however, have a marked enhancement in cell-surface expression of MerTK ( Figure 4C), which plays an important role in efferocytosis in advanced atherosclerotic lesions (9,10,27). CaMKII-KO macrophages also had an increase in Mertk mRNA ( Figure 4D).…”

Section: Resultsmentioning

confidence: 97%

“…Studies have shown that macrophage-mediated efferocytosis is defective in advanced human plaques that have not yet ruptured (7,8). Further, experiments using genetically engineered mice, i.e., mice that lack the key macrophage efferocytosis receptor MerTK, have demonstrated a causal relationship between defective macrophage-mediated efferocytosis and plaque necrosis (9,10). Recently, our group has demonstrated that MerTK expression is decreased in symptomatic carotid artery lesions as compared with asymptomatic lesions (9).…”

Section: Introductionmentioning

confidence: 99%

“…Further, experiments using genetically engineered mice, i.e., mice that lack the key macrophage efferocytosis receptor MerTK, have demonstrated a causal relationship between defective macrophage-mediated efferocytosis and plaque necrosis (9,10). Recently, our group has demonstrated that MerTK expression is decreased in symptomatic carotid artery lesions as compared with asymptomatic lesions (9). The mechanisms that contribute to defective efferocytosis in advanced atherosclerosis, however, have not yet been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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CAMKIIγ suppresses an efferocytosis pathway in macrophages and promotes atherosclerotic plaque necrosis

Doran¹,

Özcan²,

Cai³

et al. 2017

Journal of Clinical Investigation

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Section: Discussionsupporting

confidence: 85%

Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

CAMKIIγ suppresses an efferocytosis pathway in macrophages and promotes atherosclerotic plaque necrosis

Doran¹,

Özcan²,

Cai³

et al. 2017

Journal of Clinical Investigation

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“…These soluble forms of the receptors can be detected in the blood and tissue, and may compete with membrane-form receptors for the binding of protein S and GAS6. Disruption of AXL/MERTK ligand binding or AXL/ MERTK deficiency inhibits clearance of apoptotic cells (25,26) and enhances production of inflammatory cytokines (27), leading to disease pathogenesis (28,29).…”

Section: Resultsmentioning

confidence: 99%

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage

Chang¹,

Goods²,

Askenase³

et al. 2017

Journal of Clinical Investigation

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-/-bone marrow chimeras (BMCs) at days 7 and 15 after ICH. Right: Quantification of residual hematoma volume in the WT and Ccr2 -/-BMCs. n = 11 at day 7; n = 9 at day 15. *P < 0.05 by Student's t test. (B) Cylinder test and apomorphine turning test from WT and Ccr2 -/-BMCs at day 15 after ICH. n = 6/group for cylinder test; n = 8/ group for apomorphine turning test. *P < 0.05 by Student's t test. (C) Cylinder test, neurological deficit score, and corner test in control-and anti-CCR2 antibody-treated mice at days 1 and 3 after collagenase ICH. n = 7/group. *P < 0.05 by 1-way repeated-measures ANOVA and Bonferroni's post hoc test. (D) Top: Representative coronal sections show hematoma from control-and anti-CCR2 antibody-treated WT mice after blood injection ICH at 7 days. Bottom: Quantification of hematoma volume, n = 3/ group. *P < 0.05 versus control by Student's t test. (E) Top: Representative coronal sections show hematoma in the isotype control-and anti-CCR2 antibody-treated mice from collagenase model at day 12. Bottom: Quantification of hematoma volume. n = 8/group. *P < 0.05 versus control by Student's t test. (F) The cylinder test, neurological deficit score, and corner test in isotype control-and anti-CCR2 antibody-treated ICH mice at days 3, 5, 7, 9, and 11 after collagenase ICH surgery. n = 8/group. *P < 0.05 versus isotype control group by 1-way repeated-measures ANOVA and Bonferroni's post hoc test. αCCR2, anti-CCR2 antibody.

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Dying to Defend: Neutrophil Death Pathways and their Implications in Immunity

Tu,

Ren,

Jiang

et al. 2023

Advanced Science

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Neutrophils, accounting for ≈70% of human peripheral leukocytes, are key cells countering bacterial and fungal infections. Neutrophil homeostasis involves a balance between cell maturation, migration, aging, and eventual death. Neutrophils undergo different death pathways depending on their interactions with microbes and external environmental cues. Neutrophil death has significant physiological implications and leads to distinct immunological outcomes. This review discusses the multifarious neutrophil death pathways, including apoptosis, NETosis, pyroptosis, necroptosis, and ferroptosis, and outlines their effects on immune responses and disease progression. Understanding the multifaceted aspects of neutrophil death, the intersections among signaling pathways and ramifications of immunity will help facilitate the development of novel therapeutic methods.

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MerTK receptor cleavage promotes plaque necrosis and defective resolution in atherosclerosis

Cited by 171 publications

References 39 publications

CAMKIIγ suppresses an efferocytosis pathway in macrophages and promotes atherosclerotic plaque necrosis

CAMKIIγ suppresses an efferocytosis pathway in macrophages and promotes atherosclerotic plaque necrosis

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage

Dying to Defend: Neutrophil Death Pathways and their Implications in Immunity

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