Table 1.
Modulation methods and mechanisms of macrophage polarization.
| Modulation methods | Approaches | Animal strains | Pathological status | Polarization mechanisms | Biological effects | References |
|---|---|---|---|---|---|---|
| DRUG TREATMENT | ||||||
| BIO | Intraperitoneal | SD rats | MI | Not investigated | Cardiac fibrosis↓ Cardiac function↑ |
(91) |
| N-propargyl caffeamide | Intraperitoneal | SD rats | MI | Not investigated | Infarct size↓ | (92) |
| DAPT | Intravenous | SD rats | MI | Not investigated | Arrhythmia↓ Sympathetic hyperinnervation↓ |
(93) |
| Pyridostigmine | Contained in water | Wistar rats | MI | Not investigated | Anti-oxidant enzyme activity↓ Cytokine production↓ |
(94) |
| Pyridostigmine | Contained in water | Wistar rats | MI | Not investigated | LV diastolic function↑ Parasympathetic modulation↑ Sympathetic modulation↑ |
(95) |
| Eplerenone | Intracerebroventricular | Wistar rats | MI | Not investigated | Cardiomyocyte apoptosis↓ LVEF↑ |
(96) |
| Atorvastatin | Intragastric | Wistar rats | MI | Not investigated | Arrhythmia↓ Sympathetic hyperinnervation↓ |
(97) |
| Dapagliflozin | Intragastric | Wistar rats | MI | STAT3 signaling pathway | Cardiac contractility and relaxation↑ Cardiac fibrosis↓ Oxidative and nitrosative stress↓ |
(98) |
| Nicorandil | Intragastric | Wistar rats | MI | RhoA/Rho-kinase signaling↓ | Cardiac contractility and relaxation↑ Cardiac fibrosis↓ |
(99) |
| HGF and FGF-2 contained microparticle | Intramyocardial | Wistar rats | MI | Not investigated | Angiogenesis↑ | (81) |
| Telmisartan | Intragastric | Zucker diabetic fatty rats | IR injury | Ubiquitin-proteasome system↓ | Cardiac function↑ Infarct size↓ |
(100) |
| Sitagliptin + G-CSF | Contained in food and intraperitoneal, respectively | C57/BL6 mice | MI | Not investigated | Cardiomyocyte hypertrophy↓ LV dilatation↓ |
(101) |
| Niacin | Intragastric | C57BL/6 mice | MI | PGD2/DP1 axis↑ | Cardiac function↑ | (102) |
| Hydrogen sulfide | Intraperitoneal | C57BL/6 mice | MI | Lipolysis↑fatty acid oxidation↑ | Cardiac function↑ Survival↑ |
(103) |
| IL-2/Anti-IL-2 immune complex | Intraperitoneal | C57BL/6 mice | MI | Not investigated | Cardiomyocyte apoptosis↓ Infarct size↓ LV function↑ |
(104) |
| Long-acting IL-4 complex | Intraperitoneal | C57BL/6 mice | MI | Not investigated | Angiogenesis↑ Cardiomyocyte hypertrophy↓ Connective tissue formation↑ Infarct size↓ |
(4) |
| Topiramate | Intraperitoneal | C57BL/6 mice | MI | Not investigated | Cardiac rupture↓ Collagen density↑ Infarct size↓ Survival↑ |
(105) |
| BAY 60-6583 | Intravenous | C57BL/6 mice | IR injury | PI3K/PKB pathway↑ | Infarct size↓ Inflammation↓ |
(106) |
| Suppressing IRF5 by siRNA | Intravenous | C57BL/6 mice | MI | IRF5 | Infarct healing↑ | (107) |
| IL-10 | Subcutaneous | C57BL/6J mice | MI | Not investigated | ECM deposition↓ Inflammation↓ LV function↑ |
(87) |
| Ω-Alkynyl arachidonic acid | Intraperitoneal | C57BL/6N mice | MI | Regulating cross-talk between PKM2, HIF-1α and iNOS | CK-MB↓ Infarct size↓ |
(108) |
| CRMP2 siRNA | Intravenous | ApoE−/− mice | MI | IRF5↓ | Cardiac fibrosis↓ Inflammation↓ LVEF↑ Scar size↓ Survival↑ |
(109) |
| Graphene oxide-carried IL-4 plasmid DNA | Intramyocardial | Balb/C mice | MI | Not investigated | Angiogenesis↑ Cardiac fibrosis↓ Inflammatory cell infiltration↓ LV function↑ Survival↑ |
(5) |
| Hemin formulated in designed lipid-based particles | Intravenous | Balb/C mice | MI | Not investigated | Angiogenesis↑ Infarct-related regional function↑ Scar tissue↓ |
(110) |
| Histone deacetylase inhibitor | Intraperitoneal | CD1 mice | MI | Not investigated | Angiogenesis↑ LV dilation↓ LVEF↑ |
(111) |
| FGF-9 | Intramyocardial | Db/db diabetic mice | MI | Not investigated | Cardiac function↑ Infarct size↓ Inflammation↓ |
(112) |
| Ac-SDKP | Intraperitoneal | Mice | MI | Not investigated | Cardiac function↑ Collagen deposition↓ |
(113) |
| HBSP | Subcutaneous injection | Rabbits | MI | Not investigated | Coronary atherosclerosis↓ | (114) |
| GENE MODIFICATION | ||||||
| Depletion of Caveolin-1 | Gene modification | Cav1−/− mice | MI | TGF-β/Smad2↑ | Cardiac fibrosis↑ Inflammatory cell infiltration↑ Survival↓ |
(115) |
| Depletion of Lp-PLA2 | Gene modification | BmLp-PLA−/− mice | MI | Not investigated | Angiogenesis↑ Collagen deposition↑ Infarct size↓ LVEF↑ |
(116) |
| Depletion of Wnt | Gene modification | Cfms-icre;Wlsfl/fl mice | MI | Not investigated | Angiogenesis↑ Infarct-related regional function↑ |
(117) |
| Inhibition of PTP1B | Gene modification | PTP1B−/− mice | MI | Not investigated | Angiogenesis↑ LV Diastolic function↑ Myocardial perfusion↑ |
(118) |
| MIF deficiency | Gene modification | MIF deficient mice | MI | Not investigated | Cardiac remodeling↓ Cardiac rupture↓ |
(119) |
| Urokinase plasminogen activator overexpression | Gene modification | SR-uPA mice | MI | Not investigated | Cardiac fibrosis↑ | (120) |
| CELL TRANSPLANTATION AND TISSUE ENGINEERING | ||||||
| MSCs | Intramyocardial | SD rats | MI | Not investigated | Cardiac fibrosis↓ LVEF↑ |
(121) |
| MSCs | Intramyocardial | Macrophage depletion mice | MI | Not investigated | Infarct healing↑ | (84) |
| BM-MSCs | Intravenous | NOD/SCID γ null mice | MI | IL-10 mediated | Cardiac function↑ Cardiac remodeling↓ |
(122) |
| FM-MSCs | Cell sheets | Lewis rats | MI | Not investigated | Angiogensis↑ Cardiac fibrosis↓ Cardiac function↑ |
(123) |
| Bone marrow transplantation | Intravenous | C57BL/6 mice | MI | Not investigated | Cardiac function↑ Cardiac remodeling↓ Survival↑ Wall thickness↑ |
(124) |
| Myocardial ECM patch | Sutured onto infarct area | Wistar rats | MI | Not investigated | Cardiac function↑ | (125) |
| PHB patch | Patched on epicardial | Wistar rats | MI | Not investigated | Angiogenesis↑ | (126) |
BIO, (2'Z,3'E)-6-Bromoindirubin-3'-oxime; DAPT, N-N-(3,5-difluorophenacetylL-alanyl)-S-phenylglycine-t-butyl ester; LV, left ventricular; HGF, hepatocyte growth factor; G-CSF, granulocyte-colony stimulating factor; PI3K/PKB, phosphatidylinositol 3-kinase/ protein kinase B; ECM, extracellular matrix; PKM2, pyruvate kinase isozymes M2; HIF, hypoxia-inducible factor; Inos, inducible nitric oxide synthase; CRMP2, collapsin response mediator protein 2; Ac-SDKP, N-acetyl-seryl-aspartyl-lysyl-proline; HBSP, helix B surface peptide; Smad, mothers against decapentaplegic homolog 2; Lp-PLA2, lipoprotein-associated phospholipase A2; PTP1B, protein tyrosine phosphatase 1B; MIF, macrophage migration inhibitory factor; SR-uPA, overexpression of urokinase plasminogen activator; MSCs, mesenchymal stem cells; FM-MSCs, fetal membrane-derived mesenchymal stem cells; BM-MSCs, bone marrow-derived mesenchymal stem cells; PHB, poly(3-hydroxybutyrate).