September 15, 2019

Causal Role of Oxidized Lipids in Pulmonary Hypertension Development


(electronic flourish) – Welcome, my name is Jop van Berlo, from the University of
Minnesota, and I’m here with Gregoire Ruffenach from UCLA. He is here to tell us
about his exciting findings in the area of pulmonary hypertension. – Pulmonary hypertension
is a vascular disease, a pulmonary vascular disease characterized by the increased pressure in the pulmonary vasculature only. This is due to the vascular remodeling in the distal pulmonary artery, which leads to this increased pressure. This will lead, the existing
pressure will lead, with time, to right ventricular
failure and patient death. Here we investigate the
role of oxidized lipids in pulmonary hypertension. Previously, our lab and other demonstrated that oxidized lipid is increased in the plasma of this patient and participate to the
vascular remodeling. The SMA muscles have proliferation and the inflammation that we can see in pulmonary hypertension. Now, we’re more going a little bit forward to understand how oxidized lipids work in pulmonary hypertension. We found that in fact, oxidized lipids are not only part of
the pathogenesis of … I mean, part of the pathology
of pulmonary hypertension, but they cause a role in
pulmonary hypertension, because when we feed mice
with only oxidized lipid, after three weeks they developed
pulmonary hypertension, making the oxidized lipids
a really important player in pulmonary hypertension pathogenesis. Now we are trying to
understand the mechanism by which oxidized lipids
can really trigger pulmonary hypertension, and we identify miR193 as
one of the main key player who can control the oxidized
lipid level in the plasma and also control the inflammation
and the proliferation of the SMA muscles cell. We hope that this finding will
open a new avenue of research to find new therapies to cure this disease by targeting the oxidized
lipid metabolism. – Really interesting. Can I ask a couple questions? Do you think that oxidized lipids specifically target the
pulmonary vasculature, or could it also be involved in increased vascular
resistance in other arteries throughout the body. – It’s already known that
oxidized lipid participate in arteriosclerosis. Why in this mice? Well, because this, the mice
we use, the wild type mice are usually protected
against arteriosclerosis. At this point, it seems like
the pulmonary circulation is more sensitive to oxidized lipids compared to systemic circulation. What is the difference between
the systemic circulation and the pulmonary circulation, making it more accessible
to oxidized lipid? At this point we still don’t know. – These oxidized lipids, I assume can be produced by the body, and is that indeed the case? If so, under what conditions does your body produce oxidized lipids? – We know that oxidized
lipids can be produced during injury, vascular injury and will help either to
promote the inflammation or to resolve the inflammation. Each time the oxidized
lipid can have both role as a pro-inflammatory
or anti-inflammatory, but the exact mechanism
and how oxidized lipid can play both ways, inflammatory
and anti-inflammatory, is still undergoing. – An important aspect, in my
opinion, to heart failure, is the development of increased pulmonary vascular resistance, because ultimately that
will lead to failure of the right ventricle, and
this is a condition for which we currently don’t have a
whole of therapies available. Do you think that in
patients with heart failure, the levels of oxidized
lipids might predict whether the right ventricle
will undergo failure? – Maybe, because a
recently published paper demonstrated that we have,
in pulmonary hypertension in the right ventricle,
accumulation of lipids in the right ventricle, at
which point the oxidized lipid participate in this lipid
deposition in the right ventricle, I still don’t know, but
it seems to play a role in the right ventricle failure. – A really interesting
aspect about the study that you presented, I thought, was that you can feed mice
these oxidized lipids, which suggests that it
is a dietary component. Can you maybe tell us what kinds of foods contain these oxidized lipids, and would it be beneficial to avoid taking in too many oxidized lipids? – Basically oxidized lipids can be either produced by the body, or it can be produced by oxidative stress, meaning when you cook basically, usually meat, you will start to produce some of the oxidized lipids. What we know as the Western diet, high sugar, high fat diet is
usually a pretty good source of oxidized lipids. – Excellent. That would suggest that maybe if we avoid eating too much sugar, and too much fat, and too much meat, we
could lower the levels of oxidized lipids and
thereby potentially prevent the development of pulmonary hypertension and maybe of even more detrimental effects like arteriosclerosis. Is that correct? – Yes. – Thank you very much for
explaining your exciting research. I hope that in the near
future your findings will help the American Heart Association
to accomplish its mission of fighting cardiovascular
disease and stroke. Thank you. (electronic flourish)

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