title: Icaritin Inhibits Collagen Degradation-Related Factors and Facilitates Collagen Accumulation in Atherosclerotic Lesions: A Potential Action for Plaque Stabilization.
abstract: Most acute coronary syndromes result from rupture of vulnerable atherosclerotic plaques. The collagen content of plaques may critically affect plaque stability. This study tested whether Icaritin (ICT), an intestinal metabolite of Epimedium-derived flavonoids, could alter the collagen synthesis/degradation balance in atherosclerotic lesions. Rabbits were fed with an atherogenic diet for four months. Oral administration of ICT (10 mg·kg(-1)·day(-1)) was started after two months of an atherogenic diet and lasted for two months. The collagen degradation-related parameters, including macrophages accumulation, content and activity of interstitial collagenase-1 (MMP-1), and the collagen synthesis-related parameters, including amount and distribution of smooth muscle cells (SMC) and collagen mRNA/protein levels, were evaluated in the aorta. ICT reduced plasma lipid levels, inhibited macrophage accumulation, lowered MMP-1 mRNA and protein expression, and suppressed proteolytic activity of pro-MMP-1 and MMP-1 in the aorta. ICT changed the distribution of the SMCs towards the fibrous cap of lesions without increasing the amount of SMCs. Higher collagen protein content in lesions and aorta homogenates was observed with ICT treatment compared with the atherogenic diet only, without altered collagen mRNA level. These results suggest that ICT could inhibit the collagen degradation-related factors and facilitate collagen accumulation in atherosclerotic lesions, indicating a new potential of ICT in atherosclerotic plaques.
authors.affiliation: School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China. maxzhangzk@cuhk.edu.hk.
authors.forename: Zong-Kang
authors.initials: ZK
authors.lastname: Zhang
authors.affiliation: School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China. lijie@cuhk.edu.hk.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Shanghai Clinical Center of Cardiovascular and Cerebrovascular Diseases in Traditional Chinese Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China. rszbt@hotmail.com.
authors.forename: De-Xin
authors.initials: DX
authors.lastname: Yan
authors.affiliation: School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China. awnleung@cuhk.edu.hk.
authors.forename: Wing-Nang
authors.initials: WN
authors.lastname: Leung
authors.affiliation: School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China. zhangbaoting@cuhk.edu.hk.
authors.forename: Bao-Ting
authors.initials: BT
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000188:drug therapy*; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits
chemical_list: D005419:Flavonoids; D012333:RNA, Messenger; D003094:Collagen; D020781:Matrix Metalloproteinase 1; C499403:icaritin
keywords: Icaritin; atherosclerosis; collagen; matrix metalloproteinase; plaque stabilization
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