According to a study, researchers conducted a small but not insignificant number of babies are born with hearts whose muscles are spongy and thin, although exactly what causes that condition isn't clear. Now, Stanford biologists think they may have found a clue: spongy heart muscles could be the result of improperly developed blood vessels surrounding the heart. The study published in Nature Communications.
Apart from a deeper understanding of congenital heart disease, the results could shed light on how heart muscle forms in the first place, said the study's two senior authors, Ashby Morrison and Kristy Red-Horse, assistant professors of biology.
Yet Morrison, Red-Horse and their colleagues did not set out to understand congenital heart disease or to change how people thought about heart development in utero. Instead, they attribute the project to something altogether more random: their offices are right next to each other.
Time to make some mice
In yeast, the molecule, called Ino80, is important without it, yeast get sick and die off but in other organisms, "we didn't know what to expect," Morrison said. To find out, Red-Horse and her lab started the years-long process of genetically modifying mice to lack Ino80, either throughout their bodies or in specific areas of the body or specific cell types.
The most intriguing results, Red-Horse said, came from mice which didn't produce Ino80 in certain heart cells called endothelial cells that are the progenitors of blood vessels that feed the muscles of the heart.
Without Ino80, the network doesn't develop properly, and as a result, cardiac muscles couldn't develop properly either instead remaining spongy and weak. It was at this point that the team noticed the similarity between their mice and a form of heart disease called left ventricular non-compaction, the third most common disease of the heart muscle. "It was a complete surprise," Morrison said.
Curiously, blood flow through those missing vessels and the oxygen it provides is only part of the story. In a follow-up experiment, the researchers grew heart muscles in a dish along with endothelial cells that had not yet formed into blood vessels. The team found that when those endothelial cells produced no Ino80, the heart muscle didn't develop properly.
Apparently, Red-Horse said, "endothelial cells are producing something that's a growth factor" for cardiac muscle cells. "The next step is to identify that factor." Still, what they've found already should change how both doctors and biologists think about how the heart forms, Red-Horse said.
In both cases, taking into account the role of blood vessels could help explain normal muscle development in mice and then humans or lead to new therapies for diseases like left ventricular non-compaction. Research concludes that implications for regenerative medicine specialists working to grow hearts and other organs in the lab.