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Professor Yang Baofeng,
President of HMU, led the research project on The muscle-specific microRNA
miR-1 regulates cardiac arrhythmogenic potential
by targeting GJA1 and KCNJ2. For the first time in the world, the research
team found miR-1, a new target for malignant arrhythmia. They found
out its pathogenesis from the point of molecular biology, which in turn has
proved that the imbalance of miRNA is the real
cause of fatal arrhythmia. This original finding was published in Nature
Medicine last April. Two famous international cardiophysiologists
wrote a review article saying “The work of Yang is an exciting step in the
dissection of new molecular signaling pathways for arrhythmias and sudden
death.”
Heart failure and arrhythmia are leading causes
for the death of patients with heart disease. In China, there are nearly ten
million patients suffering heart failure. The four-year mortality rate
after confirmed diagnosis is up to 50%. Each year there are nearly a
million deaths from arrhythmias, most of which are caused by heart failure.
Due to differences in genetic background, living environment and disease
spectrum, some effective measures fit for the Western population are not
suitable for Chinese. Meanwhile, the four main types of antiarrhythmia
drugs used presently are not satisfactorily effective. The curative effect
of TCM only accounts for 30-60%. Therefore, it is significant to explore
the pathogenesis of heart failure and arrhythmia of Chinese population,
search for new targets for antiarrhythmia drugs
and establish an early warning system for major heart diseases and develop
effective prevention and treatment strategies.
The
project team led by Professor Yang Baofeng
targeted this difficult and hot spot in the pharmaceutical field. Through
numerous biomedical and clinical experiments, they succeeded in tracking
down a new antiarrhythmia target – miRNA. MicroRNAs (miRNAs) are endogenous noncoding
RNAs, about 22 nucleotides in length. The current understanding of the
functions of miRNAs relies mainly on their
tissue-specific or developmental stage-dependent expression and their
evolutionary conservation. Their mysterious mask has not been revealed
fundamentally. The team found that miR-1
expression was elevated (B2.8-fold) in RNA samples from individuals with
coronary artery disease compared with those from humans with healthy
hearts. To investigate whether this increase has protective or detrimental
consequences, they tested RNA samples isolated from the ischemic myocardium
of rat hearts that had been subjected to experimental myocardial
infarction, and found a similar increase in miR-1 expression in the
ischemic zone but not in the non-ischemic zone.
To
further investigate the mechanism of miRNA, the
team applied miRNA to normal in vivo model of
rats through gene transfection and found that the
rats suffered severer arrhythmia. When miRNA inhibitors
were applied, arrhythmias were evidently reduced. If miRNA
and inhibitors were applied simultaneously, the incidence of arrhythmia was
reduced as well. Arrhythmia would occur if miRNA
was transfected into the hearts of normal rats.
The study also found that miRNA caused arrhythmia
mainly through regulating certain proteins. The study has demonstrated that
miRNA is the leading cause of arrhythmia. This
will offer a new thinking for the treatment of arrhythmia and new drug
research.
Nature Medicine is one of the most
well-known journals in the world. Its impact factor is 28.9. Since
Professor Yang’s paper was published, it has aroused international
counterparts’ attention. The world famous journals such as Science, Nature and Nature Medicine
and some large-scale European and American websites published commentaries.
Dr. Mark E. Anderson and Dr. Peter J. Mohler, two
famous cardiophysiologists, commented that “The
study by Yang provides convincing evidence that miR-1 is an important regulator
of electrical remodeling and arrhythmias. The findings raise hope that
inhibition of miR-1 after myocardial infarction will reduce sudden death.”
This significant finding has aroused extensive attentions of the media at
home and abroad. It was reported on China Central Television, major
newspapers and websites.
(HMU Newspaper)
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