MicroRNAs in specialized vesicles improve heart tissue vascularization

The job of a macrophage is straightforward — as a part of the immune system, they “eat” other cells that are deemed harmful to the body. Macrophages, along with other cells, secrete small sacks of signaling molecules called vesicles, and the ones secreted by cardiac macrophages are distinct from those secreted by the other cell types found in the heart: cardiomyocytes, endothelial cells, and fibroblasts.

Wagner et al. sequenced the microRNA from cardiac vesicles to gain a better insight into how these specialized macrophages regulate homeostasis.

The discovery of microRNA — tiny fragments of RNA that regulate gene expression — won the Nobel Prize in Physiology or Medicine in 2024. Author Karl Wagner wanted to see if the microRNA found in the cardiac macrophage vesicles had anything to do with the formation of blood vessels in the heart.

“This four-way comparison helped me to really pinpoint what some of the more unique microRNAs are inside macrophages that make them stand out,” Wagner said. “And perhaps those could have some clues to how they’re regulating cell behavior in the heart.”

The researchers sequenced microRNA from vesicles secreted by the four main cardiac cell types and found that the macrophage vesicles had an abundance of two microRNAs — let-7 and 126-3p — that are known to modulate the creation of blood vessels.

They also grew a 3D cardiac tissue and introduced vesicles harvested from cardiac macrophages, and as they predicted, their addition enhanced blood vessel formation in the tissue.

“I envision this work will provide a better understanding of the way that the heart functions in a normal capacity,” Wagner said. “In addition to identifying therapeutic targets, we can speak the ‘language’ of the cells and instruct heart cells or tissues to repair themselves or improve function after disease.”

Source: “Mapping the miRNA landscape of primitive macrophage extracellular vesicles highlights their pro-vasculogenic effects in engineered human cardiac tissue,” by Karl T. Wagner, Shira Landau, Gregory M. Kent, David F. Bodenstein, and Milica Radisic, APL Bioengineering (2026). The article can be accessed at https://doi.org/10.1063/5.0313731 .