The Rogers Foundation announces a second landmark gift, building on its $130 million gift in 2014, to sustain the Ted Rogers Centre for Heart Research in perpetuity and bring the promise of precision cardiac health to patients across Canada and globally. In 2014, the...
While the many ways that heart disease
develops and progresses is complex, research has shown that one particular area
is key: the sarcoplasmic reticulum (SR). The SR governs many critical functions
in every cell – but is also responsible for biochemical changes, structural
remodeling, and deterioration when disease is present.
Yet, how the SR structures or organizes
itself is still quite unknown – particularly in cells with a highly
differentiated network: like hear, like cardiomyocytes in the heart.
A new study from the Gramolini lab at the Ted Rogers Centre for Heart Research –
in collaboration with SickKids senior scientist Ian Scott – has shone a new
light into this area. It describes how a particular protein contributes to
normal heart development and heart function, and how it regulates formation,
maintenance, and function of the SR there.
What
we now know about REEP5
That protein is called REEP5, the subject
of their paper newly
published in Nature Communications,
and it has for years been the focus of Frank Shin-Haw Lee, a University of
Toronto research trainee who earned one of the first Ted Rogers Centre’s Education Fund awards.
Lee has been investigating the role of
REEP5 in maintaining the integrity and function of highly differentiated SR in
the heart, and how it may contribute to heart failure.
“Our findings show that REEP5 plays a
critical role in regulating cellular stress responses in heart muscle cells,”
says Lee, who is a member of the Ted Rogers Centre’s Translational Biology and Engineering
Program. “When REEP5 is depleted, it destabilizes the heart and reduces the
amount of blood it is able to pump on each contraction. When we removed this
protein in both mice and zebrafish, it distorted the structure and shape of
cardiomyocytes and lead to cardiac dysfunction.”
When cardiomyocytes are under sustained stress from disease or dysfunction, cellular pathways through the SR can ultimately lead to cell death and to heart failure. This research team believes that REEP5 is a vital part of how the SR forms, how it responds to stress, how it regulates calcium (essential for heart health) and, ultimately, how the heart itself functions and develops. The more we can understand how REEP5 functions in the heart, the more we can see how heart failure may develop amidst a SR in stress.
Possible new therapies on the horizon
Sina Hadipour-Lakmehsari, co-first author
and U of T medical student, says these findings provide new insight into heart disease
in patients. “It is clearly an important protein for cardiac development and
function and, combined with future human studies, we may begin to unearth new
potential therapies,” Hadipour-Lakmehsari says. “In the lab, we can continue
studying REEP5 in genetic studies to help shed light on diseases whose causes
remain unknown.”
“This study is among the first in the world
to show that the REEP5 protein plays an essential role in the stress responses
that often lead to heart failure,” says Anthony Gramolini, principal investigator
and professor of physiology at U of T. “Deciphering the complex layers of heart
function on a cellular level will help us generate new therapeutic and
preventative strategies for heart failure.”
This research was funded by a Ted Rogers Centre Innovation Fund seed grant to Profs. Gramolini and Scott, a Natural Science and Engineering Research Council grant and a Canadian Institutes of Health Research grant to Prof. Gramolini.
Top photo: Harhsa Murthy, Frank Shin-Haw Lee, Sina Hadipour-Lakmehsari Middle photo: Anthony Gramolini, Lee, Murthy, Hadipour-Lakmehsari, Ian Scott