July 8, 2013
Dear Friend of the Texas Heart Institute,
Look closely and you will find that a key to combatting cardiovascular disease requires just that – looking very closely. Looking down to the cellular and genetic levels, in fact, has led to some exciting discoveries and continues to do so.
That is how, for instance, we broke new ground just over a
decade ago and learned that our own stem cells can be harnessed to regenerate
and repair damage in our hearts.
By looking even more closely, we also now know that as we
age, our stem cells age along with us. That means both the number of stem cells
our bodies produce and the cells' regenerative powers decline. This takes place
even as our risk of developing cardiovascular disease increases.
However, we are beginning to learn that we might be able to
reverse that process and rejuvenate stem cells at a time when our aging bodies
need them the most. Not quite the fountain of youth, but some tantalizing
I am proud to be part of a research team that has been examining
this problem and has recently discovered that by overexpressing two genes in the
stem cells of aged lab mice (with and without atherosclerosis) we were able to
increase both the proliferation of the cells and the ability of the cells to
generate new heart muscle tissue.
The research findings have just been published in the
prestigious American Heart Association journal Circulation Research.
The team specifically examined the role of overexpression of myocardin and telomerase in stem cells from bone marrow and fat tissue in aged
lab mice. These genes are involved in heart muscle regeneration and prevention
of cellular deterioration, respectively. We believe these genes might act
together to enhance cardiovascular regeneration and restore the aged cells to
their youthful capacity.
Our team also examined the effect of then transplanting these
treated stem cells into mice with restricted blood flow (ischemia) in the hind
The results were conclusive. Overexpression of myocardin and
telomerase in the aged stem cells decreased cell death and increased cell
proliferation and muscle tissue generation; that is, the aged stem cells
regained their youthful capacity. Once injected with these rejuvenated stem
cells, the mice with hind limb ischemia then showed increased blood flow and
artery capacity to their legs. (Mice were used as cell therapy recipients due
to the fact that they show similar development of atherosclerosis to humans.)
Put simply, the conclusion is that overexpression and
transplantation of these two genes may be therapeutic in rejuvenating aged stem
The research team included Dr. Rosalinda Madonna, Dr. Doris Taylor, Dr. Yong-Jian Geng, Dr. Raffaele De Caterina, Dr. Harnath Shelat, Dr. Emerson Perin, and myself.
There is more work to do, and we hope to begin testing this
process in humans in the near future. But needless to say, we are excited about
the possibilities and will continue looking very closely as we combat the
ravages of cardiovascular disease together.
Of course, we could not do it without your support, for which we are very grateful.
With respect and gratitude,
James T. Willerson, MD
President and Medical Director
Contact Dr. Willerson