title: Tongxinluo mitigates atherogenesis by regulating angiogenic factors and inhibiting vasa vasorum neovascularization in apolipoprotein E-deficient mice.
abstract: Vasa vasorum (VV) neovascularization contributes to atherogenesis and its expansion and distribution is correlated with intraplaque expression of angiogenic factors. The present study investigated the roles of Tongxinluo (TXL), a traditional Chinese medication, on VV proliferation and atherogenesis. In vitro, TXL pre-treatment reversed the tumor necrosis factor-a (TNF-a) induced expression of vascular endothelial growth factor A (VEGF-A) and angiopoietin-1 (ANGPT-1) but not ANGPT-2, leading to increased ratio of ANGPT-1 to ANGPT-2. Consistently, TXL treatment (at a dosage of 0.38, 0.75, 1.5 g/kg/d, respectively) decreased the expression of VEGF-A while increased that of ANGPT-1 in early atherosclerotic lesions of apolipoprotein E deficient (apoE-/-) mice. On aortic ring assay, microvessels sprouting from aortas were significantly inhibited in TXL-treated mice. Moreover, VV neovascularization in plaques was markedly reduced with TXL treatment. Histological and morphological analysis demonstrated that TXL treatment reduced plaque burden, plaque size and changed the plaque composition. These data suggest that TXL inhibits early atherogenesis through regulating angiogenic factor expression and inhibiting VV proliferation in atherosclerotic plaque. Our study shed new light on the anti-atherosclerotic effect of TXL.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.|The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.
authors.forename: Lianyue
authors.initials: L
authors.lastname: Ma
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ni
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Hao
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Lu
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.
authors.forename: Xingli
authors.initials: X
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.
authors.forename: Shanying
authors.initials: S
authors.lastname: Huang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.|The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.|The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Shandong University, Shandong 250012, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D042683:Angiopoietin-1 / Q000096:biosynthesis; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008297:Male; D051379:Mice; D000074085:Mice, Knockout, ApoE; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D000067996:RAW 264.7 Cells; D014651:Vasa Vasorum / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D004365:Drugs, Chinese Herbal; D042461:Vascular Endothelial Growth Factor A; C513941:tongxinluo; C467480:vascular endothelial growth factor A, mouse
keywords: Tongxinluo; atherogenesis; neovascularization; vasa vasorum