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Allied J Med Res 2017
Volume 1 Issue 2
Herbal Medicine 2017
September 01-02, 2017 London, UK
3
rd
International Conference and Expo on
Herbal & Alternative Medicine
Page 65
Role of Autophagy in Cardiac Hypertrophy:
An Insight into Use of Autophagy-Targeted
Drugs
Vandana Sankar
CSIR-National Institute for Interdisciplinary Science and Technology
(CSIR-NIIST), Kerala, India
Objective / Purpose:
Cardiovascular diseases (CVD) are
the leading cause of death in the world. The percentage
of deaths due to CVD is equivalent to that due to cancer,
COPD, diabetes and other non communicable diseases
put together. Hypertension ranks among the first risk
factors for CVD. Sustained hemodynamic load imposed
by hypertension on the heart leads to cardiac remodeling.
Hypertrophy is the first and foremost element in cardiac
remodelling. Hypertrophy, even though an adaptive
mechanism initially, leads to heart failure in the long run.
Hence prevention of hypertrophy is a major therapeutic
target. Autophagy is a cellular homeostatic process that
involves lysosome-dependent turnover of organelles
as well as proteins. Alterations in autophagy may occur
in cardiac pathologies. Efforts to target autophagy
selectively in the cardiac cells may be a logical step
towards development of novel therapeutic strategies for
the prevention of hypertrophy and thereby heart failure.
In this backdrop, the main objective of the study was to
determine the regulation of autophagy in hypertrophy
using known inhibitors and activators of autophagy.
Another objective is to test the effect of selected natural
compounds on autophagy and determine the end outcome
on hypertrophy.
Material and Methods:
Hypertrophy was induced by
exposing H9c2 cell lines (rat embryonic cardiomyoblasts)
to β-adrenergic receptor agonist, isoproterenol (ISO).
Evaluation of hypertrophy was carried out by analyzing
the size of the cells using phase contrast microscopy
and flow cytometry. Autophagy was assessed by
confocal microscopy and flow cytometry utilizing a
novel autophagy-specific dye. Rapamycin (RAP) and
chloroquine (CHL) were used as activator and inhibitor of
autophagy respectively. LC3B and LAMP2 protein markers
of autophagy were detected by immunofluorescence
microscopy and immunophenotyping. Lysosomal activity
was also measured.
Results:
ISO stimulation induced hypertrophying (27%
increase in cell size) in H9c2 cell line. Autophagy was
found to be significantly lower in ISO- stimulated cells when
compared to control. RAP showed a heightened induction
of autophagy in the cells. Surprisingly, in ISO+RAP
cotreatment group, there was a robust induction of
autophagy which was significantly higher than that of other
groups. CHL and ISO+ CHL groups showed negligible
autophagy when compared to other groups. In ISO+RAP,
the heightened autophagy induction well correlated with
increased hypertrophying of the cells (p≤0.05). There was
a proportional increase in granularity with increase in cell
size as well. Lysosomal activity was significantly higher
for ISO even though it demonstrated lower autophagic
activity. In addition, increased autophagic activity
correlated with increased lysosomal activity in ISO + RAP
group. LC3B puncta was significantly higher in ISO+CHL
indicating inhibition of LC3 turnover. Increased autophagy
(26.5% increase) could be associated with exacerbation
of hypertrophy (120% increase) as cellular hypertrophy
was found to increase significantly in ISO+RAP group.
Chloroquine, being an autophagy inhibitor, reduced
autophagy and also reduced (52%) the percentage of
hypertrophied cells. Thus it is inferred that by inhibiting
autophagy, it is possible to attenuate hypertrophy, even
though further investigations have to be done to establish
the findings.
Conclusion / Discussion:
Reduction of cardiac
hypertrophy as a strategy for prevention of cardiac failure
is a fairly novel area as till recently; regression of cardiac
hypertrophy was not attempted as it was considered to be
an adaptive change. In view of the fact that therapeutic
option for cardiac failure is limited, it is appropriate to
prevent the progression of cardiac hypertrophy to failure.
The current study is aimed to target autophagy in cardiac
hypertrophy which will hopefully provide an insight into
a potential therapeutic strategy. Moreover, studies are
aimed to test the effect of selected natural compounds on
autophagy and observe the end outcome on hypertrophy.
With the thrust given on the use of natural products and
herbal medicines and the absence of scientific records
in line with modern medicine, research in this direction
will have a great impact on the acceptance of traditional
medicine as well. I sincerely hope that the Herbal and
Alternative Medicine Conference 2017 will provide a
platform for suggestions regarding natural products that
can be used in the current study and prospects for future
collaborations.
saavan1998@gmail.comAllied J Med Res 2017