XX chromosomes may promote heart disease in women!

AlSiraj, Y., Chen, X., Thatcher, S.E. et al. XX sex chromosome complement promotes atherosclerosis in mice. Nat Commun 10, 2631 (2019). https://doi.org/10.1038/s41467-019-10462-z

Introduction

When it comes to transporting fat in the body, and artery disease, men and women differ. Females have higher levels of a hormone known as estrogen, which decreases risk of blood and heart diseases such as coronary artery disease (CAD). There is a lack of knowledge on why this is the case, however, generally, studies suggest that

A hormone that females have high levels of, known as estrogen, lowers the risk of heart disease. Scientists wanted to understand how the sex chromosomes (XX in females and XY in males) affect these factors.

They studied mice to see how sex chromosomes and hormones work differently. They found that female mice had more harmful fats in their blood and were more likely to develop heart disease than male mice. The female mice also had more enzymes in their intestines that absorbed fats, leading to higher levels of fat in their bodies. This suggests that having two X chromosomes might make it easier for the body to use fats from the diet, potentially speeding up the development of heart disease. These findings are important for understanding heart health.

Methods:

Compared to sex hormones, scientists haven't studied the genes on sex chromosomes enough to understand how they might contribute to differences in disease development between males and females. The Y chromosome in males has fewer genes, while the X chromosome, which both males and females have, contains a lot more genes, and it could play a role in causing differences in various factors and diseases.

Results:

The researchers used a mouse model to study the effects of sex chromosomes on blood fats and artery disease. Males had higher body weights than females, both before and after being fed a Western diet. Additionally, female mice had higher body weights and lean mass than male mice. Female mice had more fat mass than males.

In this study, researchers also looked at mice with different combinations of sex chromosomes and their development of artery-clogging deposits (atherosclerosis). They found that female mice had larger artery-clogging deposits compared to male mice regardless of their surgical status or diet. These findings show that having two X chromosomes can significantly influence the development of artery-clogging deposits.

Various factors were measured to understand why female mice might have higher levels of artery-clogging deposits compared to male mice. These factors included food and water intake, body weight, fat mass, and differences based on sex, or genetic background. Researchers analyzed these factors and their relationship to arteries. They found that the sex chromosomes and genetic background were the two significant factors affecting the development of atherosclerosis in the mice.

Conclusion

Our study explored the reasons behind sex differences in cardiovascular diseases, focusing on common conditions like coronary artery disease (CAD). Using mice as our model subjects, we found that female mice exhibited notably higher cholesterol levels in their blood compared to male mice. These differences were consistent across various experimental conditions, including diet variations, genetic backgrounds and bodily structure. Additionally, female mice displayed a significant increase in atherosclerosis, which is the accumulation of fatty deposits in the arteries. These findings indicate that sex chromosomes play a crucial role in how the body absorbs and processes dietary fats, potentially influencing serum lipid levels and the risk of developing heart disease. Understanding these mechanisms could offer valuable insights into sex-related disparities in cardiovascular health and pave the way for more targeted and personalized approaches to disease prevention and treatment.