Journal
BIOCHEMICAL JOURNAL
Volume 473, Issue -, Pages 1281-1295Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20150844
Keywords
atherosclerosis; extracellular matrix; inflammation; microenvironment; shear stress
Categories
Funding
- National Institute of Health [R01 HL098435, 1 U54 GM104940]
- American Heart Association [15GRNT25560056]
- American Heart Association Pre-doctoral Fellowship [14PRE18660003]
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The formation of atherosclerotic plaques in the large and medium sized arteries is classically driven by systemic factors, such as elevated cholesterol and blood pressure. However, work over the past several decades has established that atherosclerotic plaque development involves a complex coordination of both systemic and local cues that ultimately determine where plaques form and how plaques progress. Although current therapeutics for atherosclerotic cardiovascular disease primarily target the systemic risk factors, a large array of studies suggest that the local microenvironment, including arterial mechanics, matrix remodelling and lipid deposition, plays a vital role in regulating the local susceptibility to plaque development through the regulation of vascular cell function. Additionally, these microenvironmental stimuli are capable of tuning other aspects of the microenvironment through collective adaptation. In this review, we will discuss the components of the arterial microenvironment, how these components cross-talk to shape the local microenvironment, and the effect of microenvironmental stimuli on vascular cell function during atherosclerotic plaque formation.
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