Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Jul 1;319(11):1626-34.
doi: 10.1016/j.yexcr.2013.03.026. Epub 2013 Mar 28.

Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches

Caroline Baer  1 , Mario Leonardo Squadrito  1 , M Luisa Iruela-Arispe  2 , Michele De Palma  3
Affiliations
Review

Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches

Caroline Baer et al. Exp Cell Res. .

Abstract

The ability of macrophages to promote vascular growth has been associated with the secretion and local delivery of classic proangiogenic factors (e.g., VEGF-A and proteases). More recently, a series of studies have also revealed that physical contact of macrophages with growing blood vessels coordinates vascular fusion of emerging sprouts. Interestingly, the interactions between macrophages and vascular endothelial cells (ECs) appear to be bidirectional, such that activated ECs also support the expansion and differentiation of proangiogenic macrophages from myeloid progenitors. Here, we discuss recent findings suggesting that dynamic angiogenic vascular niches might also exist in vivo, e.g. in tumors, where sprouting blood vessels and immature myeloid cells like monocytes engage in heterotypic interactions that are required for angiogenesis. Finally, we provide an account of emerging mechanisms of cell-to-cell communication that rely on secreted microvesicles, such as exosomes, which can offer a vehicle for the rapid exchange of molecules and genetic information between macrophages and ECs engaged in angiogenesis.

Keywords: Angiogenesis; Blood vessel; Exosome; Heterotypic cell interaction; Macrophage; Microvesicle; Monocyte.

PubMed Disclaimer

Figures

Fig. 1 –
Fig. 1 –
Indirect and direct communication between ECs and macrophages. (A) M2-like macrophages (violet) secrete proangiogenic growth factors and proteases that facilitate EC migration and vascular growth. Furthermore, macrophages secrete microvesicles, such as exosomes, that may fuse with and deliver their cargo of proteins and RNAs to ECs, possibly influencing the angiogenic response of the blood vessel. (B) M2-like macrophages (violet) associate with adjacent vascular sprouts and “bridge” endothelial tip cells to facilitate vascular anastomosis in the developing mouse hindbrain. (C) Macrophages associate with growing blood vessels in the deep vascular plexus of the retina. Non canonical WNT signaling stimulates macrophage secretion of sFLT1, which limits vessel branching (left). In the absence of WNT signaling, excessive vessels branches are formed (right).
Fig. 2 –
Fig. 2 –
ECs support M2-like macrophage differentiation. (A) EC monolayers support the expansion of HPCs, which form myeloid cell colonies characterized by the progressive differentiation of M2-like macrophages. (B). Hypothetical model of the angiogenic vascular niche, which supports reciprocal interactions between ECs and proangiogenic, M2-like macrophages. ECs support HPC expansion (red arrow) and differentiation into M2-like macrophages (rainbow arrows); M2-like macrophages support angiogenesis by delivering proangiogenic signals to sprouting ECs.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Gordon S, Martinez FO, Alternative activation of macrophages: mechanism and functions, Immunity 32 (2010) 593–604. - PubMed
    1. Murray PJ, Wynn TA, Protective and pathogenic functions of macrophage subsets, Nat. Rev. Immunol 11 (2011) 723–737. - PMC - PubMed
    1. Pollard JW, Trophic macrophages in development and disease, Nat. Rev. Immunol 9 (2009) 259–270. - PMC - PubMed
    1. Nucera S, Biziato D, DePalma M, The interplay between macrophages and angiogenesis in development, tissue injury and regeneration, Int. J. Dev. Biol 55 (2011) 495–503. - PubMed
    1. Sunderkotter C, Steinbrink K, Goebeler M, Bhardwaj R, Sorg C, Macrophages and angiogenesis, J. Leukoc. Biol 55 (1994) 410–422. - PubMed

Publication types