Introduction
Macrophages: the shield of hearts against CVDs
Inflammation
Fibrosis
Tissue repair
Regeneration
Patient selection and target identification for macrophage-based therapies in pathological conditions
Atherosclerosis
Inflammatory macrophages
Resident-like macrophages
Foamy Trem2hi macrophages
Ischemic heart disease and myocardial infarction (MI)
Early pro-inflammatory macrophages
Late reparative macrophages
Resident macrophages (steady-state macrophages)
HFpEF (heart failure with preserved ejection fraction) and diastolic dysfunction
Profibrotic macrophages
Current status of macrophage-targeting strategies
Atherosclerosis
Depletion of monocytes/macrophages
Induction of macrophage autophagy
Adipose tissue macrophages (ATM)
Myocardial infarction
Macrophage polarization/inflammation resolution
Resident macrophage survival
HFpEF (heart failure with preserved ejection fraction) and diastolic dysfunction
Inhibition of pro-fibrotic macrophages
Non-coding RNA (ncRNA)
Class | Subclass | Biomarker | Disease |
---|---|---|---|
Inflammatory mediators | Cytokines/Chemokines | TNF-α IL-6 IL-12 MCP-1 IL-1β | |
Peroxidase enzyme | MPO | ||
Pro-fibrotic mediators | Growth factor | TGF-β GDF-15 | HFpEF [175] AHF [177] |
Glycoprotein | Galectin-3 | ||
Cell–cell network | Micro RNAs | miR-146a miR-155 | Atherosclerosis [196] HF following MI [199] |
Gene expression | CUX1 CTSD ADD3 | HF following MI [200] |
miRNAs
Long non-coding RNAs (LncRNAs) and circular RNAs (CircRNAs)
Biomarker study
Inflammatory mediators
Cytokines/chemokines
MPO
Pro-fibrotic mediators
Growth factors
Galectin-3
Others: cell-to-cell networker
Exosomes
Micro RNAs
Gene expression
Challenges and opportunity of macrophage-targeting strategies
Heterogeneity: monocyte-derived macrophages vs resident macrophages
Targeted drug delivery to tissue macrophages
Utilize tissue or cell specific promoters
Surface modification and ligand targeting
Exosome-based delivery
Ex vivo cell therapy (engineered cell therapy)
Induced pluripotent stem cell (iPSC)-derived macrophages
Autologous | Allogenic | |
---|---|---|
Cell source | Patient derived (same person) | Healthy donors |
Immune compatibility | Lower risk of rejection No immunological tests required | Higher risk of rejection Immunological tests required |
Cell characteristics | Diseased and/or heavily pretreated cells | Healthy cells |
Practicability | Less efficient since cells need to be isolated and modulated Limited production (cells are from 1 person) | Cells are prepared and ready for direct application Expansion of production possible |
Examples of application | Clinical studies: Ischemic cardiomyopathy [225] Cerebral palsy [222] Stroke [223] | Animal studies: Doxorubicin-induced heart failure in mice [215] MI treatment in mice [216] Human IPSC macrophages application in pulmonary alveolar proteinosis mice [229] |