Reduce the Hardening of Arteries due to Arteriosclerosis
Reduce the Hardening of Arteries due to Arteriosclerosis
For
the first time, a domestic research team identified the cause and therapeutic
possibility of vascular calcification. As the hardening of arteries due to accumulation
of calcium in blood vessels, vascular calcification is commonly found in arteriosclerosis
(1), diabetes, and chronic renal failure.
With the narrowing or
clogging of coronary arties that supply blood to the heart, those with angina
pectoris (2) have much difficulty with a stent procedure (3) or a coronary artery
bypass surgery (4) due to vascular calcification. But, their cause and remedy
have yet to be clarified.
Led by Prof. Kim,
Hyo-Soo, Division of Cardiology, SNU Hospital, the research team (Dr. Cho, Hyun-Ju
and Prof. Cho, Hyun-Jai) proved that vascular calcifying progenitor cells caused
vascular calcification and that vascular calcification could be cured through
activation of PPARγ (peroxisome proliferator activated receptor γ) protein
within vascular calcifying progenitor cells. Produced in the marrow, vascular
calcifying progenitor cell is the cell before differentiation into ‘osteoblast*’
(a promoter of calcium deposit in blood cells) or ‘osteoclast*’ (an inhibitor
of calcium deposit in blood vessels). Vascular calcification is controlled by
a balance between osteoblast and osteoclast.
* Osteoblast:
Located on the surface of bones, it is responsible for bone formation. While
secreting bony tissues, it turns into a bone cell enclosed with bony tissues.
*
Osteoclast: This cell dissolves bones, namely calcified cartilage and osseous
tissues.
After separating vascular calcifying progenitor cells
from the arteries of lab mice, the team divided them into four types depending
on whether they had the lab mice's stem cell marker 'stem cell antigen-1 (Sca-1)
and an antibody 'platelet-derived growth factor receptor alpha (PDGFRa).'
*
Sca-1: As a typical stem cell marker, it is widely used for animal testing.
* PDGFRa: Engaging in the differentiation of mesenchymal
stem cells, it is a marker of vascular smooth muscle cells.
After
cultivating the four types of vascular calcifying progenitor cells under certain
experimental conditions, the team looked at their differentiation into osteoclasts
for calcium dissolution in blood vessels. The progenitor cells with only Sca-1
expression (Sca-1+/PDGFRa-) were differentiated into osteoclasts.
After
confirming calcium dissolubility in blood vessels, the team activated PPARγ
in those progenitor cells (Sca-1+/PDGFRa-) via clinically approved diabetic
medication. Their differentiation into osteoclasts for calcium dissolution went
up by more than 250%.
The subjects (lab mice) were divided
into two groups. One group is injected with the progenitor cells (Sca-1+/PDGFRa-)
(Experimental Group 1), and another group underwent PPARγ activation after
injection of the same progenitor cells (Sca-1+/PDGFRa-) via diabetic medication
(Experimental Group 2). Then, the team sized up their calcification levels (5)
via CT scanning.
Experimental Group 2 recorded a more
than twofold drop of calcification via calcium deposit than Experimental Group
1. In Experimental Group 1, vascular calcifying progenitor cells were differentiated
into osteoblasts and osteoclasts while osteoblasts increased calcium in blood
vessels. In Experimental Group 2, vascular calcifying progenitor cells were
mostly differentiated into osteoclasts through PPARγ activation which dissolved
calcium deposit in blood vessels.
This
implies that certain progenitor cells sourced from the marrow can be used as
a remedy for vascular calcification and PPARγ activation via diabetes medicine
can reduce the hardening of arteries as a result of arteriosclerosis.
“We
can differentiate the vascular calcifying progenitor cells with only Sca-1 expression
into osteoblasts and osteoclasts, and particular medication can boost their
differentiation into osteoclasts rather than osteoblasts. This is expected to
contribute to reducing the hardening of blood vessels triggered by vascular
calcification,” said Prof. Kim, Hyo-Soo.
This study
appeared as a major paper with commentaries in the April 2013 issue of a world-class
academic journal 'PLOS Biology (Impact factor=12.69). It received the backing
of the Biomedical Technology Development Project spearheaded by the Ministry
of Science, ICT and Future Planning and the National Research Foundation of
Korea