Table 2.
Selected published articles related to vascular diseases regulated by macrophages
| Study | Macrophage phenotype | Model | Main intervention | Effect of intervention on prognosis | Conclusion | Citation |
|---|---|---|---|---|---|---|
| Atherosclerosis (Plaque progression) | ||||||
| Meurs et al. (2012) | CD68+ | Ldlr−/− | Abcg1−/− |
Progress (early stage) Stabilize (late stage) |
The effect of ABCG1 on the development of AS lesions seems to depend on different stages, where ABCG1 has a protective effect in early lesions, while in late atherosclerosis attenuated apoptosis and compensatory mechanisms stimulate the development of late lesions. | 322 |
| Bhat et al. (2015) | CD68+ | ApoE−/− | IL-18 treatment | Progress | IL-18 binds to IL-18 Rα via NF-κB to trigger an inflammatory cascade leading to plaque progression and destabilization. Blockade of NF-κB blocks IL-18 signaling by down-regulating IL-18, IL-18 Rα, CD36, and MMP-9, thereby reducing inflammation and restoring plaque stability by up-regulating LXR-α. | 292 |
| Tao et al. (2015) | CD68+ | ApoE−/− | SR-B1−/− | Progress | SR-B1 deficiency in macrophages promotes defective efferocytosis signaling through the Src/PI3K/Rac1 pathway, leading to inflammation and increased plaque size. | 331 |
| Ceneri et al. (2017) | F4/80+ | ApoE−/− | Rac2−/− | Progress | Macrophages rely on Rac1 to secrete IL-1β, and Rac2 prevents progressive calcification by inhibiting this pathway, thereby stabilizing plaques. | 351 |
| Oberoi et al. (2018) | CD68+ | Ldlr−/− | TNF-α antibody | Progress | TNF-α antibody reduces circulating inflammatory markers while exhibiting no impact on body weight and glucose metabolism, but increases plasma triglyceride levels and pro-atherogenic VLDL cholesterol, as well as plaque burden in the thoracoabdominal aorta and aortic root. | 286 |
| Guo et al. (2018) | CD163+ | ApoE−/− | CD163−/− | Stabilize | Through the CD163/HIF1α/VEGF-A pathway, CD163+ alternative macrophages promote plaque angiogenesis, vascular permeability and inflammation, which contributes to plaque progression. | 304 |
| Hettwer et al. (2021) | CD11b+ | ApoE−/− |
1. IL-1β antibody 2. NLRP3 inflammasome inhibition |
Both stabilize | IL-1β and NLRP3 inflammasome induce leukocyte recruitment to atherosclerotic aortas, promote bone marrow hematopoietic stem cell proliferation and inflammatory response. | 276 |
| Singla et al. (2022) | LysM+ | ApoE−/− |
1. Sirpα−/− 2. Cd47−/− 3. Cd47fl/fl LysM-Cre+/- |
1. Stabilize 2. Stabilize 3. Progress |
By inhibiting efferocytosis and the M2 macrophage phenotype, promoting cholesterol accumulation and oxidized LDL-induced inflammation, SIRPα or CD47 promotes plaque necrotic core formation. However, the opposite result is obtained with CD47-specific loss of myeloid cells. | 344 |
| Atherosclerosis (Plaque rupture) | ||||||
| Souissi et al. (2008) | CD68+ | NA | PPARα−/− | NA | By inhibiting MMP-12 expression in macrophages, PPARα agonists prevent inflammation and atherosclerotic plaque rupture. | 595 |
| Atherosclerosis (Plaque regression) | ||||||
| van Gils et al. (2012) | CD68+ | Ldlr−/− | Netrin1−/− | Regress | Through its receptor UNC5b, netrin-1 inhibits the migration of macrophages directed by chemokines CCL2 and CCL19, allowing macrophages to remain in the arterial wall to promote atherosclerosis. | 269 |
| Cardilo-Reis et al. (2012) | CD206+ and CD80+ | Ldlr−/− | IL-13 treatment | Regress | IL-13 protects against atherosclerosis and contributes to a favorable plaque morphology by increasing collagen content, reducing VCAM-1-dependent monocyte recruitment and inducing M2 macrophage polarization. | 363 |
| Mueller et al. (2018) | CD11b+ | ApoE−/− | LRP1−/− | Regress | Depletion of macrophage LRP1 enhances reverse cholesterol transport and increases the expression of the motility receptor CCR7 which drives macrophage egress from lesions, thus accelerating the regression of atherosclerosis. | 374 |
| Wang et al. (2018) | CD68+ | Ldlr−/− | β-catenin−/− | Deteriorate | Inhibition of β-catenin triggers the downregulation of STAT3 and activation of STAT1 in macrophages, which leads to elevated macrophage inflammatory response and increased atherosclerosis. | 376 |
| Aortic aneurysm (AAA) | ||||||
| Tazume et al. (2012) | CD68+ | CaCl2-induced | Angptl2−/− | Improve | By inducing the expression of proinflammatory cytokines and MMP-9, macrophage-derived Angptl2 promotes aneurysm development and vascular destruction. | 405 |
| Hadi et al. (2018) | LysM+ | Ang-II-induced | Ntn1fl/fl LysM-Cre+/- | Improve | Acting via its receptor neogenin-1, netrin-1 induces the activation of VSMC and the expression of MMP-3, thereby promoting focal ECM degradation in AAA. | 466 |
| Yan et al. (2019) | MOMA-2+ | Elastase-induced |
1. IL-12p40 antibody 2. IL-23p19 antibody |
Both improve | IL-12 and IL-23 released by macrophages promote macrophage expansion, MMP expression, Th1/Th17 cell differentiation and proliferation, thereby driving the chronic inflammatory response in AAA. | 596 |
| Wang et al. (2019) | CD68+ | CaPO4-induced | exosome inhibitor | Improve | Macrophage-derived exosomes participate in the pathogenesis of AAA by inducing the expression of MMP-2 in VSMC through JNK and p38 pathways. | 422 |
| Yang et al. (2020) | Lyz2+ |
CaCl2-induced Ang-II-induced |
Thbs1fl/fl Lyz2-Cre | Improve | Inflammatory macrophages in AAA up-regulate the expression of TSP1, which enhances macrophage infiltration by inhibiting TIMP1 expression and leads to AAA progression. | 597 |
| Salarian et al. (2023) | CD11b+ | Ang-II- induced | Mmp-12fl/fl Csf1r-iCre | Deteriorate | By activating of complement activation and neutrophil extracellular trap pathway, absence of MMP-12 leads to more pronounced elastic layer degradation and reduced collagen integrity, and ultimately adverse aortic remodeling and death from rupture. | 598 |
| Davis et al. (2023) | Lys2+ |
Elastase-induced Ang-II-induced |
Setdb2fl/fl Lys2-Cre | Improve | Macrophages in AAA significantly up-regulate the expression of SETDB2, trimethylating histone 3 lysine 9 on the TIMP1-3 gene promoters, thereby suppressing TIMP1-3 transcription and leading to unregulated matrix metalloproteinase activity, ultimately contributing to vascular inflammation, macrophage infiltration and destruction of aortic structure. | 599 |
| Ye et al. (2024) | F4/80+ | Ang-II-induced |
1. Gsdmd−/− 2. AAV-F4/80-shGSDMD |
Both improve | Macrophages in AAA express GSDMD, which promotes AAA and aortic pyroptosis. GSDMD also promoted LPS+ nigericin-induced secretion of multiple cytokines. | 600 |
CD cluster of differentiation, Ldlr low density lipoprotein receptor, ABCG1 ATP-binding cassette transporter G1, AS atherosclerosis, ApoE apolipoprotein E, IL interleukin, NF-κB nuclear factor κB, LXR liver X receptor, SR-B1 scavenger receptor class B type 1, Src proto-oncogene tyrosine-protein kinase, PI3K phosphatidylinositol-3-kinase, Rac Ras-related C3 botulinum toxin substrate, TNF-α tumor necrosis factor-α, VLDL very-low-density lipoprotein, HIF1α hypoxia inducible factor 1α, VEGF-A vascular endothelial growth factor A, NLRP3 NOD-like receptor thermal protein domain associated protein 3, SIRPα signal regulatory protein α, NA not applicable, PPAR peroxisome proliferator-activated receptor, MMP matrix metalloproteinase, CCL C-C motif chemokine ligand, VCAM-1 vascular cell adhesion molecule 1, LRP1 lipoprotein receptor-related protein 1, CCR7 C-C motif chemokine receptor 7, STAT signal transducers and activators of transduction, Angptl2 angiopoietin-like protein 2, Ang-II angiotensin-II, Ntn1 netrin-1, VSMC vascular smooth muscle cell, ECM extracellular matrix, AAA abdominal aortic aneurysms, Thbs1 thrombospondin-1, TSP1 thrombospondin-1, TIMP1 tissue inhibitors of metalloproteinase, Setdb2 SET domain bifurcated histone lysine methyltransferase 2, GSDMD gasdermin D, LPS lipopolysaccharides