Sex hormones have been suggested to play an important role in insulin sensitivity. Our results suggest that syndecan-4 may also be involved.
Carlson group

What we do

Cells in our bodies are packed with proteins that interact in networks. These networks, or signaling pathways, cause a domino effect inside the cells that affects the structure and function of the cells. The research in our group has focused on one signaling molecule that might be especially important in the female heart, called syndecan-4, which acts as a link between the exterior and interior of the cell. To better understand the molecular differences in the male and female heart, we have compared sex-dependent effects in rodents lacking this protein specifically. This is potentially important as syndecan-4 is known to associate with the incidence of heart attacks in females, but less so in males, suggesting the function of this protein varies between the sexes.

Exploring the role of syndecan-4 in the female heart

Women and men have different risk factors for the development of heart disease. Metabolic syndromes, such as diabetes, is a common risk factor for heart disease, more so in women than men. At baseline, women are more sensitive to insulin, meaning a lower concentration of insulin is needed to exert the same effect as in males.

Sex hormones have been suggested to play an important role in insulin sensitivity. Our results suggest that syndecan-4 may also be involved (Støle et al., 2022): We have recently shown that rodents missing syndecan-4 have increased serum insulin levels. Insulin is able to activate a signaling pathway called “Akt”. The Akt signaling pathway is known to promote growth of though fibrous tissue that makes it more difficult for the heart to beat, and increases the size of the heart cells causing the heart to become bigger than it should. However, an elevation in Akt signaling has been found to be protective for the heart in females due to the female hormone estrogen, whereas the opposite is true for the male heart. Interestingly, we have found that female rodents missing syndecan-4 have an increase in the Akt signaling pathway, but males do not. Various other proteins in the Akt network, involved in insulin-Akt signaling, such as GSK-3β and GLUT4, are also altered in the female rodents lacking syndecan-4 (Støle et al., 2022). We are currently investigating how these molecular changes affect hearts lacking syndecan-4 anatomically and functionally. Additionally, we are investigating how the differences we observe between the sexes play a role in the sick heart.

Through sex-inclusive research we are able to better understand how proteins such as syndecan-4 exerts its role in a sex-dependent manner, contributing to the functioning of the healthy heart and its role in the development of disease.