Implications for the role of macrophages in a model of myocardial fibrosis: CCR2−/− mice exhibit an M2 phenotypic shift in resident cardiac macrophages

Falkenham, Alec; Myers, Tanya; Wong, Chloe; Légaré, France

doi:10.1016/j.carpath.2016.05.006

Cited by 6 publications

(10 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[27][28][29] Notably, the role of MCP-1 in driving the direction of macrophage polarization has been controversial in many nonheart disease studies. [30][31][32][33][34][35][36] However, in studies related to cardiovascular disease and heart failure, the role of the MCP-1-CCR2 pathway in promoting M1 polarization and the proinflammatory effect of CCR2 + macrophages have been more widely reported, [37][38][39][40][41][42][43] which is consistent with our experimental results. We speculate that cardiomyocytes may release certain secretory factors that can collaborate with the MCP-1-CCR2 pathway and participate in M1 macrophage polarization.…”

supporting

confidence: 91%

Regulation of the Immune Microenvironment by an NLRP3 Inhibitor Contributes to Attenuation of Acute Right Ventricular Failure in Rats with Pulmonary Arterial Hypertension

Guo¹,

Qin²,

Cao³

et al. 2021

JIR

View full text Add to dashboard Cite

supporting

confidence: 91%

Regulation of the Immune Microenvironment by an NLRP3 Inhibitor Contributes to Attenuation of Acute Right Ventricular Failure in Rats with Pulmonary Arterial Hypertension

Guo¹,

Qin²,

Cao³

et al. 2021

JIR

View full text Add to dashboard Cite

“…There has been a prevailing dogma that immune cells in heart tissue were mainly derived from the circulation, which led investigators to largely disregard resident immune cells. Most studies have looked at the atrium for signs of inflammation [23, 29], however this approach has been proven to be limited and largely unable to characterize resident immune cells (MoΦ) that are increasingly recognized as an important component of heart tissue [12, 30, 31]. Also, MoΦ in particular have been shown to be capable of influencing the complex balance between inflammation and its’ resolution [32, 33].…”

Section: Discussionmentioning

confidence: 99%

“…We demonstrate that a large population of MoΦ isolated from human atrium are pro-inflammatory CD14++/CD16− (classical) with only a small proportion of CD16+ MoΦ (non-classical). Our approach to the isolation was rigorous, standardized and adapted from identical methodology previously described by our group [12, 13]. Our findings may reflect inherent differences between human and mice, most notably: mice do not express CD16 but instead Ly6c, a marker that has been necessary to identify polarity in mice [37].…”

Section: Discussionmentioning

confidence: 99%

“…Work from our group and others have shown that cellular immunity and inflammation plays a key role in myocardial disease, and is fundamental to our understanding of myocardial fibrosis, a common pathological feature of patients with heart disease [10, 12, 13]. Previous investigators have suggested that a significant amount of atrial fibrosis can be seen, and appears to correlate with inflammation and the presence of AFib [14–17].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery

Aguiar¹,

Gawdat

Legere

et al. 2019

J Transl Med

View full text Add to dashboard Cite

BackgroundThe objectives of the study were to characterize and quantify cellular inflammation and structural remodeling of human atria and correlate findings with molecular markers of inflammation and patient surrogate outcome.MethodsVoluntary participants undergoing heart surgery were enrolled in the study and blood samples were collected prior to surgery, and right atrium samples were harvested intraoperatively. Blood samples were analyzed by flow cytometry and complete blood counts. Atrial samples were divided for fixed fibrosis analysis, homogenized for cytokine analysis and digested for single cell suspension flow cytometry.ResultsA total of 18 patients were enrolled and samples assessed. Isolated cells from the atria revealed a CD45+ population of ~ 20%, confirming a large number of leukocytes. Further characterization revealed this population as 57% lymphocytes and 26% monocyte/macrophages (MoΦ), with the majority of the latter cells being classical (CD14++/CD16−). Interstitial fibrosis was present in 87% of samples and correlated significantly with patient age. Older patients (> 65) had significantly more atrial fibrosis and cellular inflammation. AFib patients had no distinguishing feature of atrial fibrosis and had significantly greater CD45+ MoΦ, increased expression of MMP9 and presented with a significant correlation in length of stay to CCL-2/MCP-1 and NLR (neutrophil-to-lymphocyte ratio).ConclusionAtrial fibrosis is correlated with age and not determinate to AFib. However, severity of atrial leukocyte infiltration and markers of matrix degradation are determinant to AFib. This also correlated with CCL2 (or MCP-1) and NLR-indicative of marked inflammation. These data show the potential importance of diagnostic and prognostic assessments that could inform clinical decision making in regard to the intensity of AFib patient management.

show abstract

“…Numerous studies have shown the connection between CCR2 and fibrosis of organs, such as liver, kidney, heart and lung 25,62‐64 . In industrialized countries, the major causes of hepatic fibrosis are alcoholism and NASH, and the degree of liver fibrosis is an important factor in determining the prognosis of chronic HBV 65 .…”

Section: Ccr2 and Liver Diseasesmentioning

confidence: 99%

Recent advances targeting C‐C chemokine receptor type 2 for liver diseases in monocyte/macrophage

刘晨

Gao

et al. 2020

Liver International

View full text Add to dashboard Cite

Liver plays a critical role in metabolism, nutrient storage and detoxification. Emergency signals or appropriate immune response leads to pathological inflammation and breaks the steady state when liver dysfunction appears, which makes body more susceptible to chronic liver infection, autoimmune diseases and tumour. Compelling proof has illustrated the non‐redundant importance of C‐C chemokine receptor type 2 (CCR2), one of G‐protein‐coupled receptors, in different diseases. Selectively expressed on the surface of cells, CCR2 is involved in various signalling pathways and regulates the migration of cells. Especially, a peculiar role of CCR2 has been identified within decades in the onset and progression of hepatic diseases, which led to particular focusing on CCR2 as a new therapeutic and diagnostic target for non‐alcoholic fatty liver disease and hepatocellular carcinoma. In this review, we discuss the effect of CCR2 in monocytes/macrophages on liver diseases. The application and translation of the decades of discoveries into therapies promise novel approaches in the treatment of liver disease.

show abstract

Implications for the role of macrophages in a model of myocardial fibrosis: CCR2−/− mice exhibit an M2 phenotypic shift in resident cardiac macrophages

Cited by 6 publications

References 24 publications

Regulation of the Immune Microenvironment by an NLRP3 Inhibitor Contributes to Attenuation of Acute Right Ventricular Failure in Rats with Pulmonary Arterial Hypertension

Regulation of the Immune Microenvironment by an NLRP3 Inhibitor Contributes to Attenuation of Acute Right Ventricular Failure in Rats with Pulmonary Arterial Hypertension

Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery

Recent advances targeting C‐C chemokine receptor type 2 for liver diseases in monocyte/macrophage

Contact Info

Product

Resources

About