Behind enemy lines: Research finds a new ally in the fight against cardiovascular disease hidden within the vessel wall itself

Date:
January 11, 2022
Source:
University of Oxford
Summary:
Researchers have discovered a new role for macrophages in the
fight against cardiovascular disease. Macrophages have mostly
been thought to drive inflammation and promote plaque build-up,
but a new study shows that a subset of macrophages is actually
fighting against plaque build-up within the artery.



FULL STORY ==========================================================================
A new study reveals the existence of a powerful ally in the fight against cardiovascular disease, a protective subset of vascular macrophages
expressing the C-type lectin receptor CLEC4A2, a molecule which fosters
"good" macrophage behaviour within the vessel wall.


========================================================================== Atherosclerosis is a chronic inflammatory disease and the main driver
of cardiovascular diseases such as stroke and heart attack. It causes
fatty substances to build up and block the arteries, restricting blood
flow and oxygen supply to vital organs. Current therapies treating atherosclerosis involves lowering cholesterol and reopening blocked
arteries. Recent studies have shown a third avenue of therapy, that
involves counteracting inflammation by targeting white blood cells.

Macrophages (from the ancient Greek "big eater") are the most abundant
white blood cell type that resides in both healthy and diseased blood
vessels. On the whole, they have been mostly thought to drive inflammation
and promote plaque build-up. However, macrophages are very heterogenous
and little is understood about their individual role in disease.

Published in Nature Communications, this new study shows that a subset
of macrophages is actually fighting against plaque build-up within
the artery.

CLEC4A2 is a molecule that is highly expressed by macrophages in blood
vessels where it fosters protective properties of macrophages by dampening excessive inflammation and ensuring lipid handling.

Inhye Park, first author, and Novo Nordisk Postdoctoral Research Fellow
at the Kennedy Institute of Rheumatology, University of Oxford said:
"Using single cell biology, we identify a C-type lectin receptor called
CLEC4A2 that determines the fate of monocytes in tissues, and drives
the tissue adaptation of macrophages with protective properties. Cell
ablation techniques showed that CLEC4A2+ macrophages limit excessive
plaque build-up. CLEC4A2 instructs macrophages to gain their identity
of resident vascular macrophages and their protective qualities that
they use to fend off atherosclerosis within the artery. CLEC4A2 not only
guides monocyte differentiation into a protective macrophage state but
also maintains homeostatic properties in macrophages." "Our findings
challenge the widely held belief that macrophages only play a harmful role
in cardiovascular disease, with the discovery that we have a powerful
ally within the vessel wall itself that can protect our arteries from
the build-up of fatty deposit," said Claudia Monaco, corresponding author
and Professor of Cardiovascular Inflammation at the Kennedy Institute.

"Understanding how we can exploit this new pathway for making new
therapies is a breakthrough to combat atherosclerosis by making the
patients' own immune system work for them rather than against them."
The study was funded by the Kennedy Trust for Rheumatology Research,
the European Commission and the Novo Nordisk Foundation.

========================================================================== Story Source: Materials provided by University_of_Oxford. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Inhye Park, Michael E. Goddard, Jennifer E. Cole, Natacha Zanin,
Leo-
Pekka Lyytika"inen, Terho Lehtima"ki, Evangelos Andreakos, Marc
Feldmann, Irina Udalova, Ignat Drozdov, Claudia Monaco. C-type
lectin receptor CLEC4A2 promotes tissue adaptation of macrophages
and protects against atherosclerosis. Nature Communications, 2022;
13 (1) DOI: 10.1038/s41467- 021-27862-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220111120440.htm

--- up 5 weeks, 3 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)