Chemical characterization of pro-inflammatory amyloid-beta peptides in human atherosclerotic lesions and platelets.
Chemical characterization of pro-inflammatory amyloid-beta peptides in human atherosclerotic lesions and platelets.
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DOI：
10.1016/j.bbadis.2011.07.004
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Roher AE
中科院分区：
文献类型：
--
作者：
Kokjohn TA;Van Vickle GD;Maarouf CL;Kalback WM;Hunter JM;Daugs ID;Luehrs DC;Lopez J;Brune D;Sue LI;Beach TG;Castaño EM;Roher AE
淀粉样蛋白(Aβ，Aβ)多肽与动脉粥样硬化性血管疾病和阿尔茨海默病的炎症病理密切相关。虽然大量的这些多肽是在外周产生的，但它们对脑外血管疾病的作用和意义还需要进一步的研究。使用顺序大小排除柱和高效液相反相方法分离了存在于人动脉粥样硬化病变壁上的淀粉样蛋白-β多肽以及激活和未激活的人血小板。用ELISA法对分离的Aβ多肽进行定量，并用MALDITOF质谱联用法进行结构分析。我们的实验表明，主动脉和血小板都含有Aβ多肽，主要是Aβ40。在动脉粥样硬化病变中，Aβ池的来源可能是活化的血小板和/或表达APP/Pn2的血管壁细胞。血浆中存在显著水平的Aβ42，这表明这个储存库对动脉粥样硬化斑块的作用很小。我们的研究结果表明，尽管主动脉粥样硬化和AD脑血管淀粉样变性的终末期表现明显不同，但这两种血管疾病都有一些关键的病理生理促进因素和途径。无论它们是沉积在中枢神经系统的血管中还是外周的动脉粥样硬化斑块中，Aβ多肽都可能促进或协同慢性炎症过程，最终导致动脉壁的退化、功能障碍和最终的破坏。
Amyloid-β (Aβ) peptides are intimately involved in the inflammatory pathology of atherosclerotic vascular disease (AVD) and Alzheimer's disease (AD). Although substantial amounts of these peptides are produced in the periphery, their role and significance to vascular disease outside the brain requires further investigation. Amyloid-β peptides present in the walls of human aorta atherosclerotic lesions as well as activated and non-activated human platelets were isolated using sequential size-exclusion columns and HPLC reverse-phase methods. The Aβ peptide isolates were quantified by ELISA and structurally analyzed using MALDI-TOF mass spectrometry procedures. Our experiments revealed that both aorta and platelets contained Aβ peptides, predominately Aβ40. The source of the Aβ pool in aortic atherosclerosis lesions is probably the activated platelets and/or vascular wall cells expressing APP/PN2. Significant levels of Aβ42 are present in the plasma, suggesting that this reservoir makes a minor contribution to atherosclerotic plaques. Our data reveal that although aortic atherosclerosis and AD cerebrovascular amyloidosis exhibit clearly divergent end-stage manifestations, both vascular diseases share some key pathophysiological promoting elements and pathways. Whether they happen to be deposited in vessels of the central nervous system or atherosclerotic plaques in the periphery, Aβ peptides may promote and perhaps synergize chronic inflammatory processes which culminate in the degeneration, malfunction and ultimate destruction of arterial walls.
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影响因子：
16.2
作者：
Cortes-Canteli, Marta;Paul, Justin;Norris, Erin H.;Bronstein, Robert;Ahn, Hyung Jin;Zamolodchikov, Daria;Bhuvanendran, Shivaprasad;Fenz, Katherine M.;Strickland, Sidney
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Strickland, Sidney
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105.7
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通讯作者：
Nissien, A
影响因子：
24
作者：
Fichtlscherer, S;Breuer, S;Zeiher, AM
通讯作者：
Zeiher, AM