Cardiac resident macrophages in cardiovascular disease: from physiology to pathology

Figure 1. Classification of cardiac resident macrophages. CCR2−cardiac resident cells are the dominant population of macrophages in the heart, which can be further divided into MHCIIlo and MHCIIhi subgroups. MHCIIlo CCR2− cardiac resident macrophages (including the three markers TimD4+, Lyve1+ and FolR2+) are present in the perivascular location, and MHCIIhi cardiac resident cells are enriched around the nerve tract. CCR2−, C-C chemokine receptor 2−; MHC, major histocompatibility complex II.

Figure 2. Regulatory mechanisms of cardiac resident macrophages in arrhythmia. Cardiac resident macrophages derived from yolk sac are involved in myocardial electrical conduction and arrhythmia through the coupling of connexin and atrioventricular node cardiomyocytes. ARGE, amphiregulin; AV, atrioventricular; Cx43, connexins 43; EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; MHC-II, major histocompatibility complex II; MEK, mitogen-activated extracellular signal-regulated kinase.

Figure 3. Regulatory mechanisms of cardiac resident macrophages in TAC. (A) Dynamic changes in the number of cardiac resident macrophages after TAC and MI; (B) the ARGE production and CCR2, CX3CR1 signalling in TAC regulate cardiac macrophage proliferation to cause cardiac hypertrophy. ARGE, amphiregulin; CCR2, C-C chemokine receptor 2; CX3CR1, chemokine C-X3-C motif receptor 1; CSF2, colony-stimulating factor 2; MI, myocardial infarction; TAC, transverse aortic constriction.

Figure 4. Regulatory mechanisms of cardiac resident macrophages in MI. The number of macrophages in the infarcted site increases significantly after AMI, and their infiltration into the infarct site occurs in three consecutive phases. Cardiac resident macrophages efficiently remove and degrade apoptotic cardiomyocytes through various pathways to ensure inflammation clearance and tissue repair. AMI, acute myocardial infarction; CCR2, C-C chemokine receptor 2; CCL2, C-C motif chemokine ligand 2; CX3CR1, chemokine C-X3-C motif receptor 1; FIZZ1, found in inflammatory zone 1; IL, interleukin; NF-κB, nuclear factor kappa-B; TNF, tumour necrosis factor; TRAF6, tumour necrosis factor receptor-associated factor 6; SIRT, sirtuins; TLR, Toll-like receptor.

Figure 5. Pericardial macrophage populations in mice and humans. The pericardial cavity of mice consists of two main populations of macrophages: Gata6+ pericardial macrophages and MHCII+ pericardial macrophages. Samples taken from the pericardial cavity of patients undergoing cardiac surgery revealed the presence of GATA6+expressing macrophages, including populations expressing CD163hi and CD163lo. MHCII, major histocompatibility complex II.

Figure 6. Modulating effect of macrophages in cardiovascular with active ingredients. Aiming at the diversity of cardiac macrophages in different cardiovascular diseases, targeted regulation of macrophages can improve myocardial damage in cardiovascular diseases. CCR2, C-C chemokine receptor 2; CDC, cardiosphere-derived cells; CX3CR1, chemokine C-X3-C motif receptor 1; Erk1, extracellular signal-regulated kinase1; EV-YF1, Y RNA fragment; IRF5, interferon regulatory factor 5; IMPs, immune-modifying microparticles; LAMP1, lysosomal-associated membrane protein 1; lncRNAs, long noncoding RNAs; MEK, mitogen-activated extracellular signal-regulated kinase; NF-κB, nuclear factor kappa-B; Nrf2, nuclear factor erythroid 2-related factor 2; NPs, nanoparticles; SIRP, signal regulatory protein-α.