Macrophage-Produced Protein Plays Essential Role in Arterial Health

Macrophages coat the surface of blood vessel to maintain their structure and function. Green: macrophage; Red: blood vessel. [Dr. Veronique Angeli]

Scientists at the National University of Singapore, Yong Loo Lin School of Medicine, say they have identified a population of macrophages that coat the outer walls of healthy arteries and express a protein called LYVE-1. The researchers found that when these cells were absent, arteries accumulate collagen and lose their elasticity, becoming inflexible.

The team reports that they demonstrated that the macrophages protect arteries from becoming stiff by showing that they interact with smooth muscle cells, which produce collagen. The interaction between the two types of cell reduces the production of collagen by the smooth muscle cells.

Veronique Angeli, Ph.D., associate professor, department of microbiology and principal investigator, immunology program, Center for Life Sciences, and colleagues demonstrated that LYVE-1 is actually responsible for this protective effect. The protein binds to hyaluronan which is expressed at the surface of smooth muscle cells and this interaction is required for the degradation of collagen by matrix metalloproteinase 9 (MMP-9).

The research (“Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen”) is published in Immunity.

“The maintenance of appropriate arterial tone is critically important for normal physiological arterial function. However, the cellular and molecular mechanisms remain poorly defined. Here, we have shown that in the mouse aorta, resident macrophages prevented arterial stiffness and collagen deposition in the steady state. Using phenotyping, transcriptional profiling, and targeted deletion of Csf1r, we have demonstrated that these macrophages—which are a feature of blood vessels invested with smooth muscle cells (SMCs) in both mouse and human tissues—expressed the hyaluronan (HA) receptor LYVE-l,” write the investigators. “Furthermore, we have shown they possessed the unique ability to modulate collagen expression in SMCs by matrix metalloproteinase MMP-9-dependent proteolysis through engagement of LYVE-1 with the HA pericellular matrix of SMCs. Our study has unveiled a hitherto unknown homeostatic contribution of arterial LYVE-1 + macrophages through the control of collagen production by SMCs and has identified a function of LYVE-1 in leukocytes.”

The work has clinical implications for both aging and cardiovascular diseases because arterial stiffness is associated with aging and precedes cardiovascular disorders such as atherosclerosis and aneurysm. This knowledge should help in the development of new treatments or the improvement of existing treatments for arterial diseases, according to Dr. Angeli.