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Message: FYI: A scientific breakthrough on the control of the bad cholesterol

FYI: A scientific breakthrough on the control of the bad cholesterol

posted on Nov 24, 2008 05:57AM

Attention News/Health Editors:

A scientific breakthrough on the control of the bad cholesterol
MONTREAL, Nov. 24 /CNW Telbec/ - A study performed by the team of Dr.
Nabil G. Seidah, Director of the Biochemical Neuroendocrinology Research Unit
at the IRCM, shows for the very first time that the degradation by PCSK9 of
the LDLR receptor, which is responsible for removing the bad cholesterol
(LDL-cholesterol) from the bloodstream, may be inhibited by a third protein,
annexin A2. This major discovery co-authored by Gaétan Mayer, a postdoctoral
fellow, Steve Poirier, a doctoral student, and Dr. Seidah was published on
November 14 in the Journal of Biological Chemistry (JBC).
Genetic studies on humans have clearly shown that PCSK9 is a prime
therapeutic target for the prevention and treatment of cardiovascular
diseases. PCSK9 proprotein convertase promotes the degradation of the receptor
responsible for eliminating LDL-cholesterol particles. Thus, the presence of
PCSK9 leads to a surplus of bad cholesterol in the bloodstream and contributes
to plaque formation, leading to blockage of blood vessels and arteries. This
phenomenon is a major risk factor that can lead to cardiovascular diseases,
such as heart attack, atherosclerosis and stroke. Mutations of human genes
have demonstrated that a rise in PCSK9 activity results in a major increase in
LDL-cholesterol and familial hypercholesterolemia. Conversely, in people with
a non-functional mutation in the gene coding for PCSK9, a decrease in its
activity brings down the LDL-cholesterol concentration levels in the
bloodstream and diminishes by up to 88% the risks of developing cardiovascular
"By performing a series of biochemical experiments, we discovered that
annexin A2 binds strongly to PCSK9 and inhibits its function," remarks Gaétan
Mayer, the article's first author. This discovery should pave the way toward
the development of a new drug that would lower blood cholesterol to
recommended levels. Currently, cholesterol lowering drugs known as "statins"
are used by more than 25 million people worldwide. Statins decrease
cholesterol synthesis and increase the number of LDL-receptors, thus
efficiently decreasing plasma cholesterol levels; however, they also increase
the amount of PCSK9, which degrades those receptors, thus reducing the effect
of statins. A drug that would block PCSK9 could either be used alone or
jointly with statins and would be highly beneficial to patients in whom
statins do not work or are unable to take this drug.
This work was supported by the Canadian Institutes of Health Research
(CIHR) and by a Canada Research Chair.

Reference: Mayer G, Poirier S, and Seidah NG. (2008) Annexin A2 is a
C-terminal PCSK9-binding protein that regulates endogenous low density
lipoprotein receptor levels. J Biol Chem, November 14; 283(46): 31791-801.

The on-line version of this article is available at: .

Dr. Nabil G. Seidah is Director of the Research Unit on Biochemical
Neuroendocrinology and Director of the Cardiovascular and Metabolic Diseases
Research Theme at IRCM. He is Director of a CIHR team on cardiovascular
disorders. He is also Full Researcher at the department of medicine at
Université de Montréal and Associate Member of the department of experimental
medicine at McGill University. Dr. Seidah is the holder of the Canada Research
Chair in Precursor Proteolysis.

Established in 1967, the IRCM ( now has 37 research units
specialized in areas as diversified as systems biology, immunity and viral
infections, cardiovascular and metabolic diseases, cancer, medicinal
chemistry, clinical research and ethical reflection. It has a staff of more
than 450. The IRCM is an independent institution, affiliated to Université de
Montréal. It has built over the years a close collaboration with McGill

For further information: Nabil G. Seidah, Ph.D., Director of the
Biochemical Neuroendocrinology Research Unit, (514) 987-5609,
[email protected];; Lucette Thériault,
Communications Director, (514) 987-5535, [email protected];

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