晚期糖基化终末产物及其受体调控Wnt/β-连环蛋白促进糖尿病动脉中膜钙化机制的研究进展_West China Medical Journal

Authors：

 张雪琳 ,  何延政 , 刘勇

泸州医学院附属医院血管外科（四川泸州, 646000）;

Corresponding author：

何延政, Email: hepda2007@vip.163.com

Keywords：

糖基化终末产物; Wnt/β-连环蛋白; 动脉中膜钙化; 血管平滑肌细胞

DOI：

10.7507/1002-0179.20140356

Video：

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动脉钙化是糖尿病、动脉粥样硬化及慢性肾功能衰竭等疾病的共同病理过程，目前认为动脉钙化形成的早期过程是一个与骨发育相似的主动的、可预防、可逆转的高度可调控的生物学过程。动脉中膜钙化发生的中心环节是血管平滑肌细胞（VSMC）向成骨样细胞的转分化，VSMC在诱导条件下可转变为成骨样细胞，并合成和分泌多种骨形成蛋白。因此，成骨细胞的诱导、抑制钙化的有关因子缺失都可导致动脉中膜钙化。目前研究表明，晚期糖基化终末产物及其受体以及Wnt/β-连环蛋白信号通路都与VSMC的表型转化、动脉中膜钙化过程有着密切的联系，但其具体分子途径尚待继续探究。

Citation： 张雪琳, 何延政, 刘勇. 晚期糖基化终末产物及其受体调控Wnt/β-连环蛋白促进糖尿病动脉中膜钙化机制的研究进展. West China Medical Journal, 2014, 29(6): 1156-1159. doi: 10.7507/1002-0179.20140356 Copy

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26.	Rutsch F, Nitschke Y, Terkeltaub R. Genetics in arterial calcification: pieces of a puzzle and cogs in a wheel[J]. Circ Res, 2011, 109(5): 578-592.

1. Kelly RP, Tunin R, Kass DA. Effect of reduced aortic compliance on cardiac efficiency and contractile function of in situ canine left ventricle[J]. Circ Res, 1992, 71(3): 490-502.
2. Ohtsuka S, Kakihana M, Watanabe H, et al. Chronically decreased aortic distensibility causes deterioration of coronary perfusion during increased left ventricular contraction[J]. J Am Coll Cardiol, 1994, 24(5): 1406-1414.
3. Watanabe H, Ohtsuka S, Kakihana M, et al. Decreased aortic compliance aggravates subendocardial ischaemia in dogs with stenosed coronary artery[J]. Cardiovasc Res, 1992, 26(12): 1212-1218.
4. Orita Y, Yamamoto H, Kohno N, et al. Role of osteoprotegerin in arterial calcification: development of new animal model[J]. Arterioscler Thromb Vasc Biol, 2007, 27(9): 2058-2064.
5. Lehto S, Niskanen L, Suhonen M, et al. Medial artery calcification. A neglected harbinger of cardiovascular complications in non-insulin-dependent diabetes mellitus[J]. Arterioscler Thromb Vasc Biol, 1996, 16(8): 978-983.
6. Enomoto M, Adachi H, Yamagishi S, et al. Positive association of serum levels of advanced glycation end products with thrombogenic markers in humans[J]. Metabolism, 2006, 55(7): 912-917.
7. Yamagishi S, Fujimori H, Yonekura H, et al. Advanced glycation endproducts accelerate calcification in microvascular pericytes[J]. Biochem Biophys Res Commun, 1999, 258(2): 353-357.
8. Cecil DL, Terkeltaub RA. Arterial calcification is driven by RAGE in Enpp1-/-mice[J]. J Vasc Res, 2011, 48(3): 227-235.
9. Tanikawa T, Okada Y, Tanikawa R, et al. Advanced glycation end products induce calcification of vascular smooth muscle cells through RAGE/p38 MAPK[J]. J Vasc Res, 2009, 46(6): 572-580.
10. Ren X, Shao H, Wei Q, et al. Advanced glycation end-products enhance calcification in vascular smooth muscle cells[J]. J Int Med Res, 2009, 37(3): 847-854.
11. Towler DA. Vascular calcification: it's all the RAGE![J]. Arterioscler Thromb Vasc Biol, 2011, 31(2): 237-239.
12. Proudfoot D, Skepper JN, Hegyi L, et al. The role of apoptosis in the initiation of vascular calcification[J]. Z Kardiol, 2001, 90(Suppl 3): 43-46.
13. Ducy P, Zhang R, Geoffroy V, et al. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation[J]. Cell, 1997, 89(5): 747-754.
14. Kim IS, Otto F, Zabel B, et al. Regulation of chondrocyte differentiation by Cbfa1[J]. Mech Dev, 1999, 80(2): 159-170.
15. Katoh Y, Periasamy M. Growth and differentiation of smooth muscle cells during vascular development[J]. Trends Cardiovasc Med, 1996, 6(3): 100-106.
16. Steitz SA, Speer MY, Curinga G, et al. Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers[J]. Circ Res, 2001, 89(12): 1147-1154.
17. Suga T, Iso T, Shimizu T, et al. Activation of receptor for advanced glycation end products induces osteogenic differentiation of vascular smooth muscle cells[J]. J Atheroscler Thromb, 2011, 18(8): 670-683.
18. Rajamannan NM, Subramaniam M, Caira F, et al. Atorvastatin inhibits hypercholesterolemia-induced calcification in the aortic valves via the Lrp5 receptor pathway[J]. Circulation, 2005, 112(Suppl 9): I229-I234.
19. Shao JS, Cheng SL, Pingsterhaus JM, et al. Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals[J]. J Clin Invest, 2005, 115(5): 1210-1220.
20. Cheng SL, Shao JS, Halstead LR, et al. Activation of vascular smooth muscle parathyroid hormone receptor inhibits Wnt/beta-catenin signaling and aortic fibrosis in diabetic arteriosclerosis[J]. Circ Res, 2010, 107(2): 271-282.
21. Al-Aly Z, Shao JS, Lai CF, et al. Aortic Msx2-Wnt calcification cascade is regulated by TNF-alpha-dependent signals in diabetic Ldlr^-/-mice[J]. Arterioscler Thromb Vasc Biol, 2007, 27(12): 2589-2596.
22. Yoon YW, Kang TS, Lee BK, et al. Pathobiological role of advanced glycation endproducts via mitogen-activated protein kinase dependent pathway in the diabetic vasculopathy[J]. Exp Mol Med, 2008, 40(4): 398-406.
23. Shang L, Ananthakrishnan R, Li Q, et al. RAGE modulates hypoxia/reoxygenation injury in adult murine cardiomyocytes via JNK and GSK-3beta signaling pathways[J]. PLoS One, 2010, 5(4): e10092.
24. Ge S, Zeng R, Luo Y, et al. Role of protein kinase C in advanced glycation end products-induced epithelial-mesenchymal transition in renal proximal tubular epithelial cells[J]. J Huazhong Univ Sci Technolog Med Sci, 2009, 29(3): 281-285.
25. Ishibashi T, Kawaguchi M, Sugimoto K, et al. Advanced glycation end product-mediated matrix metallo-proteinase-9 and apoptosis via renin-angiotensin system in type 2 diabetes[J]. J Atheroscler Thromb, 2010, 17(6): 578-589.
26. Rutsch F, Nitschke Y, Terkeltaub R. Genetics in arterial calcification: pieces of a puzzle and cogs in a wheel[J]. Circ Res, 2011, 109(5): 578-592.

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West China Medical Journal

晚期糖基化终末产物及其受体调控Wnt/β-连环蛋白促进糖尿病动脉中膜钙化机制的研究进展

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