- Dilated cardiomyopathy (DCM) is a heart disease
of unknown etiology, characterized by dilation of the heart chambers and
ending in heart failure.
- A genetic cause has been often implicated, but
the disease remains poorly understood.
- Mapping the changes in protein signaling pathways
that lead to dilated cardiomyopathy has helped researchers identify the
molecular pathology involved.
- This knowledge will help in early diagnosis and
development of new forms of treatment for the disease.
The molecular pathology
behind dilated cardiomyopathy has been determined by uncovering altered protein
signaling pathways in the disease, in a recent research undertaken at the
University of Toronto
Outline of The Study
Led by Professors Andrew
Emili and Anthony Gramolini, the team of researchers mapped alterations in
protein signaling pathways in heart cells that cause dilated cardiomyopathy (DCM)
has led to a better understanding of the processes causing dilated
cardiomyopathy, and heart failure
‘Mapping alterations in protein signaling pathways in the heart that cause dilated cardiomyopathy have led to better understanding of the disease.’
About Protein Phosphorylation - Basis of the Study
Proteins are end
products of genes and govern all critical processes in the cell. Various functions of the cell
are regulated by complex signaling networks between thousands of different
The activity of these
proteins is regulated by a process termed 'phosphorylation'
the addition of a phosphate group to it. By comparing the patterns of
protein phosphorylation in normal and DCM hearts, it is possible to gain
insight into the processes involved
, and consequently a better
understanding of the disease.
"We decided to
measure global protein phosphorylation in heart tissue to get a sense for how
signaling pathways differ between DCM and normal hearts," said Dr. Uros
Kuzmanov, who spearheaded the project as a postdoctoral research fellow in both
Emili and Gramolini labs. No similar study has been undertaken on such a large
of the Study
As a model for human
disease, Kuzmanov used mice that carry a mutation, similar to one found in
human patients, that makes them develop all the clinical features of DCM.
To get a better
knowledge of how the disease is initiated, the researchers collected heart
samples from young adult healthy and diseased mutant mice, at a time when their
heart muscles just began to dilate, for a side-by-side comparative study. They
then ground the heart tissue to separate out the proteins, which were then fed
into a mass spectrometer to be counted.
Based on the changes in
the levels of thousands of phosphorylated proteins, the researchers unraveled
hundreds of signaling pathways that were altered in DCM hearts. This is the
first detailed map of molecular signaling events, that have gone awry in DCM and
Future Research Plans
As a next step, the teams
plan to carry out a similar study in human tissue
. If, as expected, they
are able to find similar changes in the same signaling pathways in patients'
hearts, then the human map could indeed help scientists in further research
focusing on new drug targets or biomarkers for early detection.
"We expect to be
able to detect specific changes in signaling pathways in different cardiac
patients," said Kuzmanov. "And our approach is not limited to the DCM
-- it could be applied to all heart disease."
is a disease affecting the heart muscle, of unknown etiology. It begins in the
left ventricle, which begins to dilate and thin out. As a result, it is unable
to pump blood as efficiently as a normal heart would.
Dilated cardiomyopathy has no cure, but
medications to control symptoms of heart failure and prevent complications are
administered. Occasionally, a pacemaker
may be implanted to control
abnormal rhythm (arrhythmia) of the heart.
The knowledge gained by
this study, and similar ones may bring us a step closer to targeting drugs or
other forms of treatment for dilated cardiomyopathy.
- Dilated Cardiomyopathy (DCM) - (http://www.heart.org/HEARTORG/Conditions/More
- Dilated Cardiomyopathy Causes - (http://www.mayoclinic.org/diseases-conditions/dilated-cardiomyopathy/basics/causes/con-20032887)
- About Dilated Cardiomyopathy - (https://www.bhf.org.uk/heart-health/conditions/cardiomyopathy/dilated-cardiomyopathy)