Natural History of Experimental Coronary Atherosclerosis and Vascular Remodeling in Relation to Endothelial Shear Stress

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. Methods and Results—Intravascular ultrasound-based 3D reconstruction of all major coronary arteries (n=15) was serially performed in-vivo in five swine, 4, 11, 16, 23 and 36 weeks after induction of diabetes and hyperlipidemia. The reconstructed arteries were divided into 3mm-long segments (n=304). ESS was calculated in all segments at all time points using computational fluid dynamics. Vascular remodeling was assessed at each time point in all segments containing significant plaque, defined as maximal intima-media thickness (maxIMT)≥0.5mm, at week 36 (n=220). Plaque started to develop at week 11 and progressively advanced towards 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. Address for Correspondence: Peter H. Stone, MD Cardiovascular Division Brigham and Women's Hospital Harvard Medical School 75 Francis Street, Boston, MA 02115 Tel: 857 307 1963 Fax: 857 307 1955 [email protected].