The physical force of blood flow may contribute to the development of transthyretin amyloid cardiomyopathy (ATTR-CM), according to a recent study published in the International Journal of Biological Macromolecules.
Transthyretin (TTR) is a protein that normally helps carry important substances through the blood. In ATTR-CM, TTR loses its shape and forms clumps called amyloid fibrils, which build up in the heart. These clumps can also accumulate in the nerves, causing a condition called transthyretin amyloid polyneuropathy (ATTR-PN). Some genetic changes in the TTR protein are linked to ATTR-CM, while others are linked to ATTR-PN.
In this study, researchers used a laboratory setup that mimics the movement of blood through blood vessels. They found that the physical force of moving blood can cause TTR proteins to clump together.
Interestingly, TTR proteins with genetic changes known to cause ATTR-CM, such as the V122I variant, were more likely to form harmful clumps when exposed to this kind of mechanical force. In contrast, TTR proteins with the V30M mutation, which is usually linked to ATTR-PN, were more stable.
“This study provides valuable insights into the role of mechanical stress in TTR-related cardiomyopathy,” the researchers said.
Read more about ATTR-CM causes and risk factors
The researchers also tested the effect of mechanical force on TTR under acidic conditions — a method often used in past studies — but found no major differences between TTR proteins with different mutations.
“This also underscores the importance of conducting studies under physiological conditions, which are more biologically relevant and may uncover previously overlooked phenomena,” the researchers said.
Importantly, the study showed that medications like tafamidis, which help stabilize TTR and prevent it from clumping, were effective even when mechanical stress was present. This is good news for patients, as it highlights the potential of these treatments to prevent or slow down ATTR-CM.
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