Natural history of experimental coronary atherosclerosis and vascular remodeling in relation to endothelial shear stress: a serial, in vivo intravascular ultrasound study.
BACKGROUND
The natural history of heterogeneous atherosclerotic plaques and the role of local hemodynamic factors throughout their development are unknown. We performed a serial study to assess the role of endothelial shear stress (ESS) and vascular remodeling in the natural history of coronary atherosclerosis.


RESULTS
Intravascular ultrasound-based 3-dimensional reconstruction of all major coronary arteries (n=15) was performed serially in vivo in 5 swine 4, 11, 16, 23, and 36 weeks after induction of diabetes mellitus and hyperlipidemia. The reconstructed arteries were divided into 3-mm-long segments (n=304). ESS was calculated in all segments at all time points through the use of computational fluid dynamics. Vascular remodeling was assessed at each time point in all segments containing significant plaque, defined as maximal intima-media thickness >/=0.5 mm, at week 36 (n=220). Plaque started to develop at week 11 and progressively advanced toward heterogeneous, multifocal lesions at all subsequent time points. Low ESS promoted the initiation and subsequent progression of plaques. The local remodeling response changed substantially over time and determined future plaque evolution. Excessive expansive remodeling developed in regions of very low ESS, further exacerbated the low ESS, and was associated with the most marked plaque progression. The combined assessment of ESS, remodeling, and plaque severity enabled the early identification of plaques that evolved to high-risk lesions at week 36.


CONCLUSIONS
The synergistic effect of local ESS and the remodeling response to plaque formation determine the natural history of individual lesions. Combined in vivo assessment of ESS and remodeling may predict the focal formation of high-risk coronary plaque.
Koskinas
Konstantinos C
KC
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.
Feldman
Charles L
CL
Chatzizisis
Yiannis S
YS
Coskun
Ahmet U
AU
Jonas
Michael
M
Maynard
Charles
C
Baker
Aaron B
AB
Papafaklis
Michail I
MI
Edelman
Elazer R
ER
Stone
Peter H
PH
D000818:Animals; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000503:physiopathology*; D003326:Coronary Circulation / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000453:epidemiology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D011237:Predictive Value of Tests; D012307:Risk Factors; D013314:Stress, Mechanical; D013552:Swine; D018084:Ultrasonography, Interventional; D020257:Ventricular Remodeling / Q000502:physiology*