​One disease that X chromosome escape genes partially İzmir Escort

 One disease that X chromosome escape genes partially regulate is aortic valve stenosis, 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 to pump blood and can ultimately lead to heart failure. Much like a person trying to push open a door with rusty hinges, the heart gets tired. There are currently no effective drugs available to slow or halt AVS disease symptoms.

Hearts with aortic valve stenosis must pump harder to push blood through a narrowed aortic valve to the rest of the body. Credit: SuneErichsen/Wikimedia Commons, İzmir Escort

My lab studies how sex chromosomes can affect cardiovascular conditions like AVS. Previous studies have shown that the valves of people with XX versus XY chromosomes can stiffen in different ways. Generally, people with XX chromosomes have increased scarring, called fibrosis, whereas people with XY chromosomes have increased calcium deposits. Given these differences, I suspected that giving the same drug to everyone might not be the best way to treat AVS. But what could be causing these differences?

By and large, researchers think sex hormones drive sex differences in valve tissue stiffening. Indeed, decreasing estrogen levels during menopause can exacerbate heart fibrosis. However, studies on cardiovascular disease in XX and XY mice have found that sex differences still persist even after surgically excising the reproductive organs that produce sex hormones.

My team and I hypothesized that the genes that escape X-inactivation, being unique to people with XX chromosomes, may be driving these differences in valve stiffening. To test this idea, we developed bioengineered models of valve tissue using hydrogels. Hydrogels mimic the stiffness of valve tissue better than the traditional petri dish medium, allowing us to study heart cells in an environment that more closely resembles the body.

Heart tissue with XX chromosomes has a higher concentration of cells (colored green, with blue nuclei) that promote scarring than do cells with XY chromosomes. Credit: Brian Aguado, CC BY-NC-ND

We found that the cells we grew on our hydrogel models were able to replicate the sex differences seen in valve tissue – namely, valve cells with XX chromosomes had more scarring than cells with XY chromosomes. Moreover, when we decreased the activity of genes that escaped X-inactivation, we were able to decrease scarring in XX chromosome cells.

Our next step was to use our models to determine which treatments work best for AVS based on cell sex. We found that XX valve cells were less sensitive than XY cells to these drugs that targeted genes that promote scarring. Drugs that specifically target genes that escape X-inactivation, however, have a stronger effect on XX cells.