Περίληψη:
Early detection of vascular inflammation would allow deployment of
targeted strategies for the prevention or treatment of multiple disease
states. Because vascular inflammation is not detectable with commonly
used imaging modalities, we hypothesized that phenotypic changes in
perivascular adipose tissue (PVAT) induced by vascular inflammation
could be quantified using a new computerized tomography (CT) angiography
methodology. We show that inflamed human vessels release cytokines that
prevent lipid accumulation in PVAT-derived preadipocytes in vitro, ex
vivo, and in vivo. We developed a three-dimensional PVAT analysis method
and studied CT images of human adipose tissue explants from 453 patients
undergoing cardiac surgery, relating the ex vivo images with in vivo CT
scan information on the biology of the explants. We developed an imaging
metric, the CT fat attenuation index (FAI), that describes adipocyte
lipid content and size. The FAI has excellent sensitivity and
specificity for detecting tissue inflammation as assessed by tissue
uptake of 18F-fluorodeoxyglucose in positron emission tomography. In a
validation cohort of 273 subjects, the FAI gradient around human
coronary arteries identified early subclinical coronary artery disease
in vivo, as well as detected dynamic changes of PVAT in response to
variations of vascular inflammation, and inflamed, vulnerable
atherosclerotic plaques during acute coronary syndromes. Our study
revealed that human vessels exert paracrine effects on the surrounding
PVAT, affecting local intracellular lipid accumulation in preadipocytes,
which can be monitored using a CT imaging approach. This methodology can
be implemented in clinical practice to noninvasively detect plaque
instability in the human coronary vasculature.
Συγγραφείς:
Antonopoulos, Alexios S.
Sanna, Fabio
Sabharwal, Nikant and
Thomas, Sheena
Oikonomou, Evangelos K.
Herdman, Laura and
Margaritis, Marios
Shirodaria, Cheerag
Kampoli, Anna-Maria and
Akoumianakis, Ioannis
Petrou, Mario
Sayeed, Rana and
Krasopoulos, George
Psarros, Constantinos
Ciccone, Patricia and
Brophy, Carl M.
Digby, Janet
Kelion, Andrew
Uberoi, Raman
and Anthony, Suzan
Alexopoulos, Nikolaos
Tousoulis, Dimitris and
Achenbach, Stephan
Neubauer, Stefan
Channon, Keith M. and
Antoniades, Charalambos
