Yasir Al-Siraj: My name is Yasir. I'm a Ph.D. candidate in the Department of Pharmacology
and Nutritional Sciences at the University of Kentucky, and I had been here since 2012.
The research in Dr. Lisa Cassis's lab mainly focusing on the sex
differences in obesity-induced hypertensions and abdominal aortic aneurysms, and the novelty
of our works, and the discovery of these genes that may identify a sex-specific therapeutic
to treat some cardiovascular diseases, made us successful
to renew our fund from the National Institute of Heath.
Cardiovascular diseases are the leading cause of death in the world.
And, significant sex differences exist in the development of several cardiovascular diseases, including
hypertension, Abdominal Aortic Aneurysm, and atherosclerosis. And, most of the investigators
that are studying the sex differences, are mainly focusing on the sex hormones. However,
the genes that are on the sex chromosomes, represent another fundamental difference between
males and females, but no one has looked at it in relation to the vascular diseases. 'Cause,
the males are always born with XY sex chromosome complement,
while the females are always born with an XX.
Abdominal aortic aneurysm. It's a permanent dilation in the abdominal
regions of the aorta. The aorta is the largest artery in the body, and it is the biggest
supplier of blood. This disease, affecting more than 1.1 million people in the United
States that are aged between 50 and 84. And, there's an 85 percent chance of death if it
gets ruptured. And, the male sex is considered the strongest, non-modifiable risk factor
for this disease. And, that's a big sex difference. That's why we're trying to understand why
the males are more susceptible, and why the females are protected from this disease.
In this study, we try to answer the question, what will happen if we
put the male sex chromosome complement, which is the XY, in a female mouse, in relation
to AAA. So, our hypothesis in this study, is that the presence of a XY sex chromosome
complement in female mouse, will augment the development and severity of AAA.
And, in this study, we have used a novel mouse model that enables us to produce an XX or XY females,
both of them, they have ovaries. And, then we remove their sex organs in order to remove
the effects of their sex hormones. And, in this way, we'll be able to study the pure
sex chromosome effects. First, in the initial studies, we tried to define the differences
between the gene expressions in the abdominal aortas from XX versus XY females. And, we
found that genes that are involved in the inflammatory pathways are highly expressed
in abdominal aortas from XY females. And, then when we infuse the XY females with angiotensin II
in order to induce the AAA formations, we found that AAA incidence and the rupture were doubled.
So, in order to mimic the male environment, we administer
testosterone to the XY females, and we infuse them with angiotensin II. We found that, over
70 percent of XY females were dying due to rupture. And, these effects were associated
with degrees in the oxidative stress, and matrix metalloproteineases
activities in the aorta from XY females.
The result from this study indicates genes on the sex chromosome
complement regulate the aortic vascular biology. And, in most importantly, it has therapeutic
complications for the use of sex hormones in aging populations, in transgender individuals,
and potentially may identify a sex-specific therapeutic that may be used to treat common
cardiovascular diseases. And most importantly, this study advanced the basic knowledge of
sex chromosome effects on vasculature.
We have identified two gene targets that we are going to test the efficacy
of either blocking, or stimulating, them. Again, the formation and the progressions of AAA.
I was very excited to get my paper published in this journal.
Because, this journal has high impact factors, and it is very respectful in the scientific
community. And, this journal has only an 8 percent acceptance rate, with a bias towards
the clinical studies. So, the fact that my paper get accepted in this journal, that mean
that there is a high quality of work, and a relevance to the human disease.