Aging heart cells offer clues to susceptibility of older people to
severe COVID-19

Date:
August 18, 2020
Source:
University of Cambridge
Summary:
Genes that play an important role in allowing SARS-CoV-2 to invade
heart cells become more active with age, according to new research.



FULL STORY ========================================================================== Genes that play an important role in allowing SARS-CoV-2 to invade heart
cells become more active with age, according to research published today
in the Journal of Molecular and Cellular Cardiology. The findings could
help explain why age is major risk factor for dying from COVID-19,
with people over 70 years at greatest risk, and why the disease can
cause heart complications in severe cases, including heart failure and inflammation of the heart.


========================================================================== "When this novel coronavirus first emerged, we expected it to be
primarily a respiratory illness, as the virus usually takes hold first
in the lungs," said Professor Anthony Davenport from the Department
of Medicine. "But as the pandemic has progressed, we've seen more and
more COVID-19 patients - - particularly older patients -- affected by
heart problems. This suggests that the virus is capable of invading and damaging heart cells and that something changes as we age to make this possible." Professor Davenport led an international team of researchers
from the University of Cambridge, Maastricht University, KU Leuven and Karolinska Institute to investigate the link between COVID-19 and heart failure. The researchers examined cells known as cardiomyocytes to see
how susceptible they were to infection by the coronavirus. Cardiomyocytes
make up the heart muscle and are able to contract and relax, enabling the
heart to pump blood around the body. Damage to these cells can affect
the ability of the heart muscles to perform, leading to heart failure
To cause damage, the virus must first enter the cell. SARS-CoV-2 is a coronavirus -- spherical in shape with 'spike' proteins on its surface,
which it uses to gain entry. The spike protein binds to ACE2, a protein receptor found on the surface of certain cells. The virus is also able
to hijack other proteins and enzymes, including TMPRSS2 and Cathepsins
B and L to gain entry.

The researchers compared cardiomyocytes from five young (19-25 year old)
males and five older (63-78 year old) males and found that the genes that
give the body instructions to make these proteins were all significantly
more active in cardiomyocytes from the older males. This suggests that
there is likely to be an increase in the corresponding proteins in aged cardiomyocytes.

"As we age, the cells of our heart muscles produce more of the proteins
needed by the coronavirus to break into our cells," said Dr Emma Robinson
from Maastricht University and KU Leuven. "This makes these cells more vulnerable to damage by the virus and could be one reason why age is a
major risk factor in patients infected with SARS-CoV-2." Some of the
proteins encoded by the genes can be inhibited by existing medicines. For example, the anti-inflammatory drug camostat inhibits TMPRSS2 and has
been shown to block SARS-CoV-2 entry in cells grown in the laboratory.

The study also suggests new targets for medicines that could be developed
such as compounds blocking binding of the virus to ACE2 that may be
beneficial in protecting the heart.

"The more we learn about the virus and its ability to hijack our cells,
the better placed we are to block it, either with existing drugs or by developing new treatments," said Professor Davenport.

The study was funded by grants including from Wellcome, the British
Heart Foundation and Dutch Heart Foundation.


========================================================================== Story Source: Materials provided by University_of_Cambridge. The original
story is licensed under a Creative_Commons_License. Note: Content may
be edited for style and length.


========================================================================== Journal Reference:
1. Emma L. Robinson, Kanar Alkass, Olaf Bergmann, Janet J. Maguire, H.

Llewelyn Roderick, Anthony P. Davenport. Genes encoding ACE2,
TMPRSS2 and related proteins mediating SARS-CoV-2 viral entry are
upregulated with age in human cardiomyocytes. Journal of Molecular
and Cellular Cardiology, 2020; DOI: 10.1016/j.yjmcc.2020.08.009 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200818114952.htm

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