State-of-the-Art Paper
Role of Endothelial Shear Stress in the Natural History of Coronary Atherosclerosis and Vascular Remodeling: Molecular, Cellular, and Vascular Behavior

https://doi.org/10.1016/j.jacc.2007.02.059Get rights and content
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Although the entire coronary tree is exposed to the atherogenic effect of the systemic risk factors, atherosclerotic lesions form at specific arterial regions, where low and oscillatory endothelial shear stress (ESS) occur. Low ESS modulates endothelial gene expression through complex mechanoreception and mechanotransduction processes, inducing an atherogenic endothelial phenotype and formation of an early atherosclerotic plaque. Each early plaque exhibits an individual natural history of progression, regression, or stabilization, which is dependent not only on the formation and progression of atherosclerosis but also on the vascular remodeling response. Although the pathophysiologic mechanisms involved in the remodeling of the atherosclerotic wall are incompletely understood, the dynamic interplay between local hemodynamic milieu, low ESS in particular, and the biology of the wall is likely to be important. In this review, we explore the molecular, cellular, and vascular processes supporting the role of low ESS in the natural history of coronary atherosclerosis and vascular remodeling and indicate likely mechanisms concerning the different natural history trajectories of individual coronary lesions. Atherosclerotic plaques associated with excessive expansive remodeling evolve to high-risk plaques, because low ESS conditions persist, thereby promoting continued local lipid accumulation, inflammation, oxidative stress, matrix breakdown, and eventually further plaque progression and excessive expansive remodeling. An enhanced understanding of the pathobiologic processes responsible for atherosclerosis and vascular remodeling might allow for early identification of a high-risk coronary plaque and thereby provide a rationale for innovative diagnostic and/or therapeutic strategies for the management of coronary patients and prevention of acute coronary syndromes.

Abbreviations and Acronyms

EC
endothelial cell
ECM
extracellular matrix
eNOS
endothelial nitric oxide synthase
ESS
endothelial shear stress
IEL
internal elastic lamina
IL
interleukin
LDL
low-density lipoprotein cholesterol
MAPK
mitogen-activated protein kinase
MMP
matrix metalloproteinase
NF-κB
nuclear factor-kappa B
NO
nitric oxide
ROS
reactive oxygen species
SREBP
sterol regulatory elements binding protein
TCFA
thin cap fibroatheroma
TF
transcription factor
VSMC
vascular smooth muscle cell

Cited by (0)

1

Dr. Stone receives research grants from Boston Scientific Co., Novartis Pharmaceutical Co., and the National Institutes of Health (NIH).

2

Dr. Feldman receives research grants from Boston Scientific Co. and Novartis Pharmaceutical Co.

3

Dr. Edelman is receiving a research grant from the National Institutes of Health (R01 HL 49039).