Eosinophils protect pressure overload- and β-adrenoreceptor agonist-induced cardiac hypertrophy

Yang, Chengzhang; Li, Jie; Deng, Zhiyong; Luo, Songyuan; Liu, Jing; Fang, Wenqian; Liu, Feng; Liu, Tianxiao; Zhang, Xian; Zhang, Yuanyuan; Meng, Zhaojie; Zhang, Shuya; Luo, Juhua; Liu, Conglin; Yang, Dafeng; Liu, Lijun; Sukhova, Galina K.; Sadybekov, Anastasiia; Katritch, Vsevolod; Libby, Peter; Wang, Jing; Guo, Junli; Shi, Guo‐Ping

doi:10.1093/cvr/cvac060

Cited by 10 publications

(6 citation statements)

References 48 publications

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“…We have recently reported a role of EOS in AAA and cardiac repair during myocardial infarction and cardiac hypertrophy. [ 11,44,60 ] ILC2 may use the same mechanisms demonstrated in this study to produce IL5 to control EOS development as an indirect mechanism that protects hearts from infarct injury‐associated cardiac dysfunction.…”

Section: Discussionmentioning

confidence: 86%

Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils

et al. 2023

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Development of abdominal aortic aneurysms (AAA) enhances lesion group‐2 innate lymphoid cell (ILC2) accumulation and blood IL5. ILC2 deficiency in Rorafl/flIl7rCre/+ mice or induced ILC2 depletion in Icosfl‐DTR‐fl/+Cd4Cre/+ mice expedites AAA growth, increases lesion inflammation, but leads to systemic IL5 and eosinophil (EOS) deficiency. Mechanistic studies show that ILC2 protect mice from AAA formation via IL5 and EOS. IL5 or ILC2 from wild‐type (WT) mice, but not ILC2 from Il5−/− mice induces EOS differentiation in bone‐marrow cells from Rorafl/flIl7rCre/+ mice. IL5, IL13, and EOS or ILC2 from WT mice, but not ILC2 from Il5−/− and Il13−/− mice block SMC apoptosis and promote SMC proliferation. EOS but not ILC2 from WT or Il5−/− mice block endothelial cell (EC) adhesion molecule expression, angiogenesis, dendritic cell differentiation, and Ly6Chi monocyte polarization. Reconstitution of WT EOS and ILC2 but not Il5−/− ILC2 slows AAA growth in Rorafl/flIl7rCre/+ mice by increasing systemic EOS. Besides regulating SMC pathobiology, ILC2 play an indirect role in AAA protection via the IL5 and EOS mechanism.

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Section: Discussionmentioning

confidence: 86%

Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils

et al. 2023

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“… 41 Human ECP and EDN share similar tertiary sequence structure and surface charges with mEar1. 17 mEar1 binding on BMPR-1A/1B and less efficiently on BMPR-2 suggests that human ECP and EDN also use BMPR-1A, BMPR-1B, and possibly BMPR-2 as their receptors on vascular SMC. After human vascular SMCs were treated with ECP followed by immunoprecipitation with ECP antibody, we performed immunoblot analyses with various antibodies and found that human ECP formed complexes with BMPR-1A and BMPR-1B, but not BMPR-2 or TGFBR1/2 ( Figure 7A ).…”

Section: Resultsmentioning

confidence: 99%

“…Our recent study showed that donor eosinophils remained high for 7 days after adoptive transfer in recipient mouse hearts but lowered after 14 days. 17 Therefore, each recipient mouse received six doses of 1 × 10 7 donor eosinophils by intravenous (i.v.) injection starting at day 0 before being fed an atherogenic diet and two weeks thereafter.…”

Section: Methodsmentioning

confidence: 99%

“…Eosinophils were cultured as previously reported. 17 , 18 Briefly, bone-marrow cells were collected from mouse femurs and tibias, centrifuged for 5 min at 300 g, followed by lysing red blood cells (RBCs) by pipetting cell pellet up and down twice in 9 mL sterile H 2 O and then immediately adding 1 mL of 10 × PBS. Once RBCs were lysed, cells were suspended in 10 mL 1 × PBS and counted.…”

Section: Methodsmentioning

confidence: 99%

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Cationic proteins from eosinophils bind bone morphogenetic protein receptors promoting vascular calcification and atherogenesis

Meng

Zhang

et al. 2023

European Heart Journal

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Aims Blood eosinophil count and eosinophil cationic protein (ECP) concentration are risk factors of cardiovascular diseases. This study tested whether and how eosinophils and ECP contribute to vascular calcification and atherogenesis. Methods and results Immunostaining revealed eosinophil accumulation in human and mouse atherosclerotic lesions. Eosinophil deficiency in ΔdblGATA mice slowed atherogenesis with increased lesion smooth muscle cell (SMC) content and reduced calcification. This protection in ΔdblGATA mice was muted when mice received donor eosinophils from wild-type (WT), Il4−/−, and Il13−/− mice or mouse eosinophil-associated-ribonuclease-1 (mEar1), a murine homologue of ECP. Eosinophils or mEar1 but not interleukin (IL) 4 or IL13 increased the calcification of SMC from WT mice but not those from Runt-related transcription factor-2 (Runx2) knockout mice. Immunoblot analyses showed that eosinophils and mEar1 activated Smad-1/5/8 but did not affect Smad-2/3 activation or expression of bone morphogenetic protein receptors (BMPR-1A/1B/2) or transforming growth factor (TGF)-β receptors (TGFBR1/2) in SMC from WT and Runx2 knockout mice. Immunoprecipitation showed that mEar1 formed immune complexes with BMPR-1A/1B but not TGFBR1/2. Immunofluorescence double-staining, ligand binding, and Scatchard plot analysis demonstrated that mEar1 bound to BMPR-1A and BMPR-1B with similar affinity. Likewise, human ECP and eosinophil-derived neurotoxin (EDN) also bound to BMPR-1A/1B on human vascular SMC and promoted SMC osteogenic differentiation. In a cohort of 5864 men from the Danish Cardiovascular Screening trial and its subpopulation of 394 participants, blood eosinophil counts and ECP levels correlated with the calcification scores of different arterial segments from coronary arteries to iliac arteries. Conclusion Eosinophils release cationic proteins that can promote SMC calcification and atherogenesis using the BMPR-1A/1B-Smad-1/5/8-Runx2 signalling pathway.

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“…Recently, animal studies have suggested that increased eosinophils play a role in tissue protection against heart and liver injury. [33][34][35] Thus, it is also possible that interstitial eosinophilic aggregates in the kidney represent a protective response to an active disease status. Whether eosinophils play a protective or harmful role may depend on the target organs and the specific pathological context.…”

Section: Discussionmentioning

confidence: 99%

Interstitial Eosinophilic Aggregates and Kidney Outcome in Patients with CKD

Hattori,

Sakaguchi,

Oka

et al. 2023

CJASN

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Background Interstitial eosinophilic aggregates are observed in various kidney diseases, but their clinical implications remain unknown. We assessed the association between interstitial eosinophilic aggregates and kidney outcomes and further analyzed the association between blood eosinophil count, as a surrogate for interstitial eosinophilic aggregates, and the risk of kidney failure in patients with advanced CKD. Methods We analyzed datasets from two retrospective cohort studies: (1) the kidney biopsy cohort including 563 patients who underwent native kidney biopsy at Osaka University Hospital between 2009 and 2021 and (2) the retrospective CKD cohort including 2877 patients with an eGFR of 10–60 ml/min per 1.73 m2 referred to the nephrology outpatient center at Osaka University Hospital between 2005 and 2018. Interstitial eosinophilic aggregates were defined as ≥5 interstitial eosinophils in the high-power field on hematoxylin and eosin staining. This study outcome was initiation of KRT or ≥40% decline in eGFR. Results In the kidney biopsy cohort, interstitial eosinophilic aggregates were found in 17% of patients, most frequently in those with diabetic nephropathy (50%). Interstitial eosinophilic aggregates were associated with a higher rate of the composite kidney outcome after adjustment for clinical and histological variables (hazard ratio, 3.61; 95% confidence interval, 2.47 to 5.29; P < 0.001). LASSO revealed that blood eosinophil count was the strongest predictor of interstitial eosinophilic aggregates. In the retrospective CKD cohort, higher baseline and time-updated blood eosinophil counts were significantly associated with a higher rate of KRT initiation in Cox proportional hazards models and marginal structural models. Conclusions Interstitial eosinophilic aggregates were associated with a higher risk of a composite of KRT initiation or ≥40% decline in eGFR.

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Eosinophils protect pressure overload- and β-adrenoreceptor agonist-induced cardiac hypertrophy

Cited by 10 publications

References 48 publications

Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils

Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils

Cationic proteins from eosinophils bind bone morphogenetic protein receptors promoting vascular calcification and atherogenesis

Interstitial Eosinophilic Aggregates and Kidney Outcome in Patients with CKD

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