Integrins and Monocyte Migration to the Ischemic Myocardium

Sopel, Mryanda; Ma, Irene; Gelinas, Laura; Oxner, Adam; Myers, Tanya; Légaré, Jean‐François

doi:10.3109/08941930903469425

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…The early stage of myocardial infarction involves massive infiltration of inflammatory cells mainly into the peri-infarct region [18]. Macrophages play a role in the removal of the necrotic tissue and in the initiation of a healing process.…”

Section: Discussionmentioning

confidence: 99%

The Transient Receptor Potential Vanilloid 2 Cation Channel Is Abundant in Macrophages Accumulating at the Peri-Infarct Zone and May Enhance Their Migration Capacity towards Injured Cardiomyocytes following Myocardial Infarction

et al. 2014

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PurposeA novel family of transient receptor potential (TRP) channels, that may hold a role in calcium homeostasis, has recently been described. By employing a GeneChip array analysis we have demonstrated a clear and specific upregulation of the TRP vanilloid 2 (TRPV2) mRNA in the left ventricles (LV) 3–5 days post-acute myocardial infarction (MI) compared to sham-operated controls, both in rats and in mice. We sought to characterize the cardiac cellular subpopulations in which TRPV2 is overexpressed upon acute MI.MethodsLewis rats underwent an acute MI by ligation of the left anterior descending artery or chest opening only (sham). The animals were terminated at various time points and an immunohistochemical (IHC) and immunofloerescent (IFC) staining of the LV sections as well as a flow cytometry analysis of LV-derived cells were carried out, using anti-TRPV2 and anti-monocyte/macrophage antibodies. Rat alveolar macrophage cells, NR8383, transiently transfected with TRPV2 siRNA were allowed to migrate towards hypoxic conditioned media of the rat cardiac myoblast line H9C2 using a trans-well migration assay. The macrophage cells migrating to the bottom side of the inserts were counted.ResultsThe IHC and IFC staining as well as the flow cytometry data demonstrated a substantial expression of TRPV2 in infiltrating macrophages in the peri-infarct region 3–5 days post-acute MI. The in vitro migration assay data demonstrated that following inhibition of the TRPV2 channel, the number of migrating macrophages towards conditioned medium of hypoxic cardiomyocytes was significantly reduced.ConclusionsTRPV2 is highly expressed on the peri-infarct infiltrating macrophages and may play an important role in post-MI phagocytosis. Better characterization of this channel may pave the way for identifying a new target for modulating the dramatic post-MI immune reactions.

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Section: Discussionmentioning

confidence: 99%

The Transient Receptor Potential Vanilloid 2 Cation Channel Is Abundant in Macrophages Accumulating at the Peri-Infarct Zone and May Enhance Their Migration Capacity towards Injured Cardiomyocytes following Myocardial Infarction

et al. 2014

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“…This process has been shown to be critically mediated by monocytes, which mature to active macrophages at the inflammatory site. Thus, monocytes have recently drawn considerable attention as a target to improve post-AMI repair [1, 2]. It has recently been demonstrated that CD14 + - expressing macrophages predominantly accumulate at the infarct zone twelve hours- five days following the ischemic event [3].…”

Section: Introductionmentioning

confidence: 99%

TRPV2 knockout mice demonstrate an improved cardiac performance following myocardial infarction due to attenuated activity of peri-infarct macrophages

et al. 2017

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BackgroundWe have recently shown that the expression of the transient receptor potential vanilloid 2 channel, TRPV2, is upregulated in the peri-infarct zone 3–5 days following an acute myocardial infarction (AMI). Further analysis has demonstrated that invading monocytes maturing to macrophages merely harbor the documented elevated expression of this channel.PurposeAssess cardiac function in TRPV2-KO mice compared to TRPV2-WT following AMI and analyze the potential involvement of TRPV2-expressing macrophages in the recovery process.MethodsTRPV2-KO or WT mice were induced with AMI by ligation of the left anterior descending artery (LAD). In another set of experiments, TRPV2-KO mice induced with AMI, were intravenously (IV) injected with WT or TRPV2-KO peritoneal macrophages in order to directly assess the potential contribution of TRPV2-expressing macrophages to cardiac healing. Cardiac parameters were obtained by echocardiography 1 day and 30 days post infarction. The relative changes in the ejection fraction (EF) and additional cardiac parameters between baseline (day 1) and day 30 were calculated and statistical significance was determined (SPSS).ResultsThe in vivo study showed that while EF was significantly decreased in the WT animals between baseline and day 30, EF was only slightly and insignificantly reduced in the KO animals. Likewise LVESD and LVESA were significantly modified exclusively in the WT animals. Moreover, intravenous administration of peritoneal WT macrophages, but not KO macrophages, significantly reduced survival of post-MI TRPV2-KO mice.ConclusionThe data suggest that knockout of the TRPV2 channel may attenuate macrophage-dependent pro-inflammatory processes and result in better cardiac recovery. TRPV2 may thus represent a novel therapeutic target for treatment of patients undergoing an acute MI.

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“…Clinical studies have demonstrated that monocytes play a key role in atherosclerosis [6,7], myocardial infarction (MI) [8], and healing after MI [9]. Monocytes are attracted to the coronary artery wall, where they differentiate to macrophages, become loaded with lipids, and remain trapped there.…”

Section: Introductionmentioning

confidence: 99%

Polymorphism rs7023923 and monocyte count in blood donors and coronary artery disease patients

et al. 2015

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Integrins and Monocyte Migration to the Ischemic Myocardium

Abstract: Significant ED1+ mononuclear cell migration within 24 hr of MI correlated with peak MCP-1 mRNA. Monoclonal antibody blockade suggested that early mononuclear cell migration is dependent only in part on alpha4 and beta2 integrins.

Cited by 6 publications

References 35 publications

The Transient Receptor Potential Vanilloid 2 Cation Channel Is Abundant in Macrophages Accumulating at the Peri-Infarct Zone and May Enhance Their Migration Capacity towards Injured Cardiomyocytes following Myocardial Infarction

The Transient Receptor Potential Vanilloid 2 Cation Channel Is Abundant in Macrophages Accumulating at the Peri-Infarct Zone and May Enhance Their Migration Capacity towards Injured Cardiomyocytes following Myocardial Infarction

TRPV2 knockout mice demonstrate an improved cardiac performance following myocardial infarction due to attenuated activity of peri-infarct macrophages

Polymorphism rs7023923 and monocyte count in blood donors and coronary artery disease patients

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