title: Tanshinone II A stabilizes vulnerable plaques by suppressing RAGE signaling and NF-κB activation in apolipoprotein-E-deficient mice.
abstract: Tanshinone II A (TSIIA) is a diterpene quinone extracted from the roots of Salvia miltiorrhiza with anti-inflammatory and anti‑oxidant properties that is used to treat atherosclerosis. In the current study, morphological analyses were conducted to evaluate the effects of TSIIA on atherosclerotic vulnerable plaque stability. Additionally, receptor of advanced glycation end products (RAGE), adhesion molecule, and matrix‑metalloproteinases (MMPs) expression, and nuclear factor-κB (NF‑κB) activation were examined in apolipoprotein E (apoE)‑deficient mice treated with TSIIA. Eight‑week‑old apoE-/- mice were administered TSIIA and fed an atherogenic diet for 8 weeks. TSIIA exhibited no effects on plaque size. Analysis of the vulnerable plaque composition demonstrated decreased numbers of macrophages and smooth muscle cells, and increased collagen content in apoE‑deficient mice treated with TSIIA compared with untreated mice. Western blotting revealed that TSIIA downregulated the expression levels of vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule‑1 (ICAM‑1), and MMP‑2, ‑3, and ‑9, suppressed RAGE, and inhibited NF‑κB, JNK and p38 activation. The present study demonstrated that the underlying mechanism of TSIIA stabilization of vulnerable plaques involves interfering with RAGE and NF‑κB activation, and downregulation of downstream inflammatory factors, including ICAM‑1, VCAM‑1, and MMP‑2, ‑3 and ‑9 in apoE-/- mice.
authors.affiliation: Department of Geriatric Medicine, China‑Japan Friendship Hospital, Beijing 100029, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, China‑Japan Friendship Hospital, Beijing 100029, P.R. China.
authors.forename: Lufang
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Dermatology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Medical Sciences, China‑Japan Friendship Hospital, Beijing 100029, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Third Department of Internal Medicine, Changping Chinese and Western Medicine Hospital, Beijing 102208, P.R. China.
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Geriatric Medicine, China‑Japan Friendship Hospital, Beijing 100029, P.R. China.
authors.forename: Tiezhong
authors.initials: T
authors.lastname: Zhang
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D045784:Abietanes; D001057:Apolipoproteins E; D018836:Inflammation Mediators; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; C021751:tanshinone; D020782:Matrix Metalloproteinases