Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney

Area of Science:

• Immunology
• Nephrology
• Vascular Biology

Background:

• Renal artery stenosis (RAS) causes microvascular damage, but the specific macrophage populations involved in repair versus injury remain unclear.
• Macrophages play dual roles in tissue repair and injury, necessitating identification of distinct functional subsets within the kidney.

Purpose of the Study:

• To characterize distinct macrophage populations in the kidney and elucidate their roles in renal artery stenosis (RAS).
• To investigate the pro-angiogenic potential of kidney-resident macrophages (KRMs) and their relevance in human RAS.

Main Methods:

• Transcriptional profiling and fate-mapping studies to distinguish murine kidney macrophage subsets.
• Murine model of RAS, liposomal clodronate treatment, bone marrow transplantation, and RNA-sequencing.
• Analysis of human kidney biopsies from RAS patients and correlation with kidney function.

Main Results:

• Identified long-lived kidney-resident macrophages (KRMs) and transient monocyte-derived macrophages.
• In RAS, KRMs self-renewed and showed enrichment in pro-angiogenic pathways, while monocyte-derived macrophages increased and correlated with capillary loss.
• KRMs promoted renal peritubular endothelial cell proliferation in vitro, and human KRMs were increased in RAS patients, inversely correlating with kidney function.

Conclusions:

• Kidney-resident macrophages (KRMs) possess pro-angiogenic properties and expand during renal artery stenosis (RAS).
• KRMs may play a protective role in stenotic kidney injury by promoting vascular repair and maintaining kidney function.
• Targeting KRMs could offer a therapeutic strategy for managing renal artery stenosis (RAS).