Specific macrophage populations promote both cardiac scar deposition and subsequent resolution in adult zebrafish.

Aims: A robust inflammatory response to tissue injury is a necessary part of the repair process but the deposition of scar tissue is a direct downstream consequence of this response in many tissues including the heart. Adult zebrafish not only possess the capacity to regenerate lost cardiomyocytes but also to remodel and resolve an extracellular scar within tissues such as the heart, but this scar resolution process remains poorly understood. This study aims to characterize the scarring and inflammatory responses to cardiac damage in adult zebrafish in full and investigate the role of different inflammatory subsets specifically in scarring and scar removal.

Artificial cell membrane binding thrombin constructs drive in situ fibrin hydrogel formation.

Cell membrane re-engineering is emerging as a powerful tool for the development of next generation cell therapies, as it allows the user to augment therapeutic cells to provide additional functionalities, such as homing, adhesion or hypoxia resistance. To date, however, there are few examples where the plasma membrane is re-engineered to display active enzymes that promote extracellular matrix protein assembly. Here, we report on a self-contained matrix-forming system where the membrane of human mesenchymal stem cells is modified to display a novel thrombin construct, giving rise to spontaneous fibrin hydrogel nucleation and growth at near human plasma concentrations of fibrinogen.

Plaque Size Is Decreased but M1 Macrophage Polarization and Rupture Related Metalloproteinase Expression Are Maintained after Deleting T-Bet in ApoE Null Mice.

Background: Thelper1 (Th1) lymphocytes have been previously implicated in atherosclerotic plaque growth but their role in plaque vulnerability to rupture is less clear. We investigated whether T-bet knockout that prevents Th1 lymphocyte differentiation modulates classical (M1) macrophage activation or production of matrix degrading metalloproteinases (MMPs) and their tissue inhibitors, TIMPs.

Methods & Results: We studied the effect of T-bet deletion in apolipoproteinE (ApoE) knockout mice fed a high fat diet (HFD) or normal chow diet (ND).

Classical and Alternative Activation and Metalloproteinase Expression Occurs in Foam Cell Macrophages in Male and Female ApoE Null Mice in the Absence of T and B Lymphocytes.

Background: Rupture of advanced atherosclerotic plaques accounts for most life-threatening myocardial infarctions. Classical (M1) and alternative (M2) macrophage activation could promote atherosclerotic plaque progression and rupture by increasing production of proteases, including matrix metalloproteinases (MMPs). Lymphocyte-derived cytokines may be essential for generating M1 and M2 phenotypes in plaques, although this has not been rigorously tested until now.