TY - JOUR
T1 - Atherosclerotic plaque destabilization
T2 - Mechanisms, models, and therapeutic strategies
AU - Silvestre-Roig, Carlos
AU - De Winther, Menno P.
AU - Weber, Christian
AU - Daemen, Mat J.
AU - Lutgens, Esther
AU - Soehnlein, Oliver
PY - 2014/1/3
Y1 - 2014/1/3
N2 - Understanding the pathophysiology of atherogenesis and the progression of atherosclerosis have been major goals of cardiovascular research during the previous decades. However, the complex molecular and cellular mechanisms underlying plaque destabilization remain largely obscure. Here, we review how lesional cells undergo cell death and how failed clearance exacerbates necrotic core formation. Advanced atherosclerotic lesions are further weakened by the pronounced local activity of matrix-degrading proteases as well as immature neovessels sprouting into the lesion. To stimulate translation of the current knowledge of molecular mechanisms of plaque destabilization into clinical studies, we further summarize available animal models of plaque destabilization. Based on the molecular mechanisms leading to plaque instability, we outline the current status of clinical and preclinical trials to induce plaque stability with a focus on induction of dead cell clearance, inhibition of protease activity, and dampening of inflammatory cell recruitment.
AB - Understanding the pathophysiology of atherogenesis and the progression of atherosclerosis have been major goals of cardiovascular research during the previous decades. However, the complex molecular and cellular mechanisms underlying plaque destabilization remain largely obscure. Here, we review how lesional cells undergo cell death and how failed clearance exacerbates necrotic core formation. Advanced atherosclerotic lesions are further weakened by the pronounced local activity of matrix-degrading proteases as well as immature neovessels sprouting into the lesion. To stimulate translation of the current knowledge of molecular mechanisms of plaque destabilization into clinical studies, we further summarize available animal models of plaque destabilization. Based on the molecular mechanisms leading to plaque instability, we outline the current status of clinical and preclinical trials to induce plaque stability with a focus on induction of dead cell clearance, inhibition of protease activity, and dampening of inflammatory cell recruitment.
KW - atherosclerosis
KW - efferocytosis
KW - macrophages
KW - necrotic core
KW - neutrophils
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U2 - 10.1161/CIRCRESAHA.114.302355
DO - 10.1161/CIRCRESAHA.114.302355
M3 - Review article
AN - SCOPUS:84892935256
SN - 0009-7330
VL - 114
SP - 214
EP - 226
JO - Circulation research
JF - Circulation research
IS - 1
ER -