Protein that blocks body's ability to clear bad cholesterol identified
Researchers are now looking to develop a drug that will boost existing
statin drugs to prevent heart disease

Date:
April 1, 2021
Source:
University of Alberta Faculty of Medicine & Dentistry
Summary:
Researchers have uncovered a long-sought link in the battle to
control cholesterol and heart disease. The protein that interferes
with low- density lipoprotein (LDL) receptors that clear 'bad'
cholesterol from the blood was identified. Excess LDL cholesterol
can lead to atherosclerosis -- a narrowing and hardening of arteries
-- and ultimately, heart attack.



FULL STORY ==========================================================================
A team of researchers at the University of Alberta has uncovered a
long-sought link in the battle to control cholesterol and heart disease.


==========================================================================
The protein that interferes with low-density lipoprotein (LDL) receptors
that clear "bad" cholesterol from the blood was identified in findings
recently published in Nature Communications by Dawei Zhang, associate
professor of pediatrics in the Faculty of Medicine & Dentistry. Excess
LDL cholesterol can lead to atherosclerosis -- a narrowing and hardening
of arteries -- and ultimately, heart attack.

"We have known for many years that these receptors could be cleaved,
but nobody knew which protein was responsible," said Zhang. "There had
been several attempts around the world but nobody else was successful."
Now that the culprit has been identified, Zhang's lab is already at work
to find a drug to target the protein, allowing the receptors to clear
more LDL.

A cholesterol-reducing class of drugs called statins -- Lipitor and
Crestor are two well-known brand names -- has been shown to reduce
cardiac events by 20 to 40 per cent, but they have side-effects that mean
they can't be given in high enough doses to work for everyone. The new
drug would be used in combination with statins to boost their effect,
Zhang said.

Zhang's team stumbled upon the role of the protein -- membrane type 1
matrix metalloproteinase -- by accident while studying another protein
involved in heart function. They then set out to repeat and confirm
their findings in mouse, rat and human cells, working in collaboration
with researchers in China and other faculty members at the U of A. Their
study was funded by the Heart and Stroke Foundation of Canada and the
Canadian Institutes of Health Research.

Zhang is also a member of the Women and Children's Health Research
Institute.

The protein has other critical physiological functions, Zhang explained,
so his lab will work to identify and focus on the specific region within
the protein that acts on the LDL receptor. They are also working with
a new technique to further target their potential drug so it will work
only within the liver, further reducing the likelihood of unwanted side-effects. Their early results are encouraging, Zhang said.

Zhang noted the protein is also critical for cancer tumour invasion,
so the team will collaborate with U of A oncology experts to learn more.

"The one protein is a shared risk factor for the two most common
diseases in humans -- cancer and cardiovascular disease,"
he said. "We will explore whether we can target one protein
to reduce the incidence of the two most common human diseases." ========================================================================== Story Source: Materials provided by University_of_Alberta_Faculty_of_Medicine_&_Dentistry.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Adekunle Alabi, Xiao-Dan Xia, Hong-Mei Gu, Faqi Wang, Shi-Jun
Deng, Nana
Yang, Ayinuer Adijiang, Donna N. Douglas, Norman M. Kneteman, Yazhuo
Xue, Li Chen, Shucun Qin, Guiqing Wang, Da-Wei Zhang. Membrane
type 1 matrix metalloproteinase promotes LDL receptor shedding
and accelerates the development of atherosclerosis. Nature
Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-22167-3 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/04/210401123917.htm

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