Humans have two sex chromosomes, X and Y, and they pair up in every cell of the body.
People with XX and XY chromosomes typically identify as male and female.
The genes on these chromosomes play a key role in development and function.
In my high school science class, I learned about a curious function of X chromosomes, and the example of a cat.
The coat color of a female calico cat is determined by the X chromosomes.
When an orange cat mates with a black cat, female offspring that inherit one X chromosomes from each parent will have a mixture of orange and black fur.
Male cats with one X and one Y chromosomes have black or orange coats.
Sex differences in fur color happen biologically. The X chromosomes from one parent are turned off in some cells, while the X chromosomes from the other parent are turned off in others.
If one X chromosomes comes from a parent with orange fur and the other from a parent with black fur, there will be orange and black fur.
Cats and people need only one X chromosomes to function properly. One of the X chromosomes is turned off in every cell to ensure the correct dosage.
Some of the genes on the X chromosomes stay turned on despite being inactivated. Up to one-third of the genes on the X chromosome in people can escape inactivation, and they are thought to play a role in regulating health and disease.
Because X-inactivation only happens in people with more than one X chromosomes, researchers like me have been looking at how the genes that escape inactivation on the second X affect the health of people with XX chromosomes. For certain conditions, cell sex may be at the center of the matter.
Aortic valve stenosis is a condition in which the part of the heart that controls blood flow to the rest of the body stiffens and narrows. This makes the heart work harder and can lead to heart failure.
The heart gets tired like a person trying to open a door. There are no effective drugs for the disease.
Sex chromosomes can affect cardiovascular conditions.
The valves of people with XX versus XY chromosomes can stiffen in different ways.
People with XX and XY chromosomes have different levels of scarring and calcium deposits.
I suspected that giving the same drug to everyone might not be the best way to treat the disease. What could be causing these differences?
Sex differences in valve tissue stiffening are thought to be caused by sex hormones. Estradiol levels can be reduced during menopause.
Sex differences persist even after excising the reproductive organs that produce sex hormones, despite studies showing cardiovascular disease in XX and XY mice.
My team and I theorize that the genes that escape X-inactivation may be the reason for the differences in valve stiffening. We created bio engineered models of valve tissue.
It is possible to study heart cells in an environment that resembles the body with the help of hydrogels.
The cells we grew on our models were able to reproduce the sex differences seen in valve tissue, but they had more scarring than cells with XY chromosomes.
When we decreased the activity of genes that escaped X-inactivation, we were able to decrease the amount of scarring.
The next step was to use our models to figure out which treatments work best.
The drugs that targeted genes that promote scarring were less sensitive to XX valve cells. Drugs that specifically target genes that escape X-inactivation have a stronger effect on XX cells.
There are sex and gender differences in cardiovascular disease. Women are less likely to be prescribed cardiovascular medications than men despite guidelines, and trans people have higher rates of heart attacks than cis people.
We are one step closer to achieving equity in the development of medical therapies for cardiovascular disease.
By taking sex chromosomes into account, my team and I believe that treatment strategies can be tailored for everyone.
The assistant professor is from the University of California San Diego.
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