Chemical characterization of pro-inflammatory amyloid-β peptides in human atherosclerotic lesions and platelets.

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

BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2011 vol. 1812 p. 1508 - 1514

0925-4439

Amyloid-β (Aβ) peptides are intimately involved in the inflammatory pathology of atherosclerotic vasculardisease (AVD) and Alzheimer´s disease (AD). Although substantial amounts of these peptides are produced inthe 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 nonactivatedhuman platelets were isolated using sequential size-exclusion columns and HPLC reverse-phasemethods. The Aβ peptide isolates were quantified by ELISA and structurally analyzed using MALDI-TOF massspectrometry 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 activatedplatelets 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 thatalthough aortic atherosclerosis and AD cerebrovascular amyloidosis exhibit clearly divergent end-stagemanifestations, 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 inthe periphery, Aβ peptides may promote and perhaps synergize chronic inflammatory processes whichculminate in the degeneration, malfunction and ultimate destruction of arterial walls.