|
|
|
|
|
The effect and mechanism of exogenous hydrogen sulfide on atherosclerosis in apolipoprotein E-/-mice |
Yang Qin, Jiang Hong, Wen Yuan, He Long-miao, Zhang Ming-xia, Huang Jun |
Department of Cardiology, the First Affiliated Hospital, Nanchang University, Nanchang 330006, China |
|
|
Abstract Objective: To investigate the regulation and mechanism of exogenous hydrogen sulfide(H2S) on atherosclerosis in ApoE-/- mice by Toll-like receptor 4(TLR4). Methods: The carotid artery atherosclerotic plaques in ApoE-/- mice model was established; the mice were fed with a high-fat diet and administered GYY4137 for 8 weeks. Lipid and atherosclerotic lesions were measured by oil red O staining. TNF-α, IL-6, IL-1 and IL-10 were detected by ELISA. Protein expression of TLR4, PI3K, Akt, P-Akt were evaluated by Western blot. Results: Compared with the control group, the lipid composition and proinflammatory factors TNF- α, IL-6 and IL-1 increased in the model group, and the inhibitory factor IL-10 decreased, and the expression of TLR4, PI3K and P-Akt protein increased in atherosclerotic plaques (P<0.01). GYY4137 medium and high dose intervention reduced the lipid composition and proinflammatory factors TNF-α, IL-6, IL-1 expression in the model group, increased the inhibitory factor IL-10, decreased the expression of TLR4, PI3K and P-Akt protein (P<0.01). The effect of LY294002 intervention was similar to that of GYY4137. Conclusion: Exogenous H2S can regulate the expression of TLR4 and TNF- α, IL-6, IL-1 and IL-10, and prevent the development of carotid atherosclerotic plaques in ApoE-/- mice, which is related to the PI3K-Akt signaling pathway.
|
Received: 01 September 2017
|
Corresponding Authors:
Huang Jun, E-mail: junhuang918@163.com
|
|
|
|
[1]Wildgruber M, Swirski FK, Zernecke A. Molecular imaging of inflammation in atherosclerosis[J]. Theranostics, 2013, 3(11): 865-884.
[2]Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity[J]. Cell, 2006, 124(4): 783-801.
[3]Yan ZQ. Regulation of TLR4 expression is a tale about tail [J]. Arterioscler Thromb Vasc Biol, 2006, 26(12): 2582-2584.
[4]von der Thüsen JH, van Berkel TJ, Biessen EA. Induction of rapid atherogenesis by perivascular carotid collar placement in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice[J]. Circulation, 2001,103(8): 1164-1170.
[5]Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strate gies[J]. Circulation, 2003,108(15): 1772-1778.
[6]Xu XH, Shah PK, Faure E, et al. Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL[J]. Circulation, 2001, 104(25): 3103-3108.
[7]Michelsen KS, Wong MH, Shah PK, et al. Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E[J]. Proc Natl Acad Sci USA, 2004, 101(29):10 679-10 684.
[8]Howell KW, Meng X, Fullerton DA, et al. Toll-like receptor 4 mediates oxidized LDL-induced macrophage differentiation to foam cells[J]. J Surg Res, 2011, 171(1):e27-31.
[9]Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis[J]. Nature, 2011, 473(7347):317-325.
[10]Konstantinidis D, Paletas K, Koliakos G, et al. Signaling components involved in leptin-induced amplification of the atherosclerosis-related properties of human monocytes[J]. J Vasc Res, 2009, 46(3): 199-208.
[11]Kim SY, Jeong E, Joung SM, et al. PI3K/Akt contributes to increased expression of Toll-like receptor 4 in macrophages exposed to hypoxic stress[J]. Biochem Biophys Res Commun, 2012, 419(3): 466-471.
[12]Xu Y, Du HP, Li J, et al. Statins upregulate cystathionine Y-lyase transcription and H2S generation via activating Akt signaling in macrophage[J]. Pharmacol Res, 2014, 87:18-25.
[13]Zhang H, Guo C, Zhang A, et al. Effect of S-aspirin, a novel hydrogen-sulfide -releasing aspirin (ACS14), on atherosclerosis in apoE-deficient mice[J]. Eur J Pharmacol, 2012, 697(1-3):106-116.
[14]Whiteman M, Li L, Rose P, et al. The effect of hydrogen sulfide donors on lipopolysaccharide induced formation of inflammatory mediators in macrophages[J]. Antioxid Redox Signal, 2010, 12(10): 1147-1154.
[15]Li L, Whiteman M, Guan YY, et al. Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (gyy4137): New insights into the biology of hydrogen sulfide[J]. Circulation, 2008, 117(18):2351-2360. |
|
|
|