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Beyond the traditional M1-M2 paradigm, current transcriptomic analyses reveal greater TAM diversity with seven main subtypes: interferon-primed TAMs (IFN-TAMs), immune regulatory TAMs (Reg-TAMs), inflammatory cytokine-enriched TAMs (Inflam-TAMs), lipid-associated TAMs (LA-TAMs), proangiogenic TAMs (Angio-TAMs), RTM-like TAMs (RTM-TAMs), and proliferating TAMs (Prolif-TAMs) ( Figure 6 ) (94)

Disrupting this pathwayeither by severing kidney sensory nerves, selectively deleting the angiotensin II type 1a receptor (AT1a) in the subfornical organ (SFO), or using optogenetics to silence the kidney-SFO or SFO-paraventricular nucleus (PVN) connectionsreduces sympathetic output, which in turn diminishes structural damage and functional impairment in the kidneys and heart in these models of CKD and heart failure (Cao et al., 2023)