Nanomolar aluminum induces expression of the inflammatory systemic biomarker C-reactive protein (CRP) in human brain microvessel endothelial cells (hBMECs).
C-reactive protein (CRP; also known as pentraxin 1, PTX1), a 224 amino acid soluble serum protein organized into a novel pentameric ring-shaped structure, is a highly sensitive pathogenic biomarker for systemic inflammation. High CRP levels are found in practically every known inflammatory state, and elevated CRP levels indicate an increased risk for several common age-related human degenerative disorders, including cardiovascular disease, cancer, diabetes, and Alzheimer's disease (AD). While the majority of CRP is synthesized in the liver for secretion into the systemic circulation, it has recently been discovered that an appreciable amount of CRP is synthesized in highly specialized endothelial cells that line the vasculature of the brain and central nervous system (CNS). These highly specialized cells, the major cell type lining the human CNS vasculature, are known as human brain microvessel endothelial cells (hBMECs). In the current pilot study we examined (i) CRP levels in human serum obtained from AD and age-matched control patients; and (ii) analyzed the effects of nanomolar aluminum sulfate on CRP expression in primary hBMECs. The three major findings in this short communication are: (i) that CRP is up-regulated in AD serum; (ii) that CRP serum levels increased in parallel with AD progression; and (iii) for the first time show that nanomolar aluminum potently up-regulates CRP expression in hBMECs to many times its 'basal abundance'. The results suggest that aluminum-induced CRP may in part contribute to a pathophysiological state associated with a chronic systemic inflammation of the human vasculature.
Russian Academy of Medical Sciences, Moscow 113152, Russia.
Peter N
PN
Alexandrov
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Theodore P A
TP
Kruck
LSU Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA 70112, USA; Department of Ophthalmology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA; Department of Neurology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA. Electronic address: wlukiw@lsuhsc.edu.
Walter J
WJ
Lukiw
D000368:Aged; D000534:Alum Compounds / Q000494:pharmacology* / Q000633:toxicity; D000544:Alzheimer Disease / Q000097:blood*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000098:blood supply*; D002097:C-Reactive Protein / Q000378:metabolism*; D002196:Capillaries / Q000166:cytology; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D000534:Alum Compounds; D015415:Biomarkers; C041524:aluminum sulfate; D002097:C-Reactive Protein
Aluminum sulfate; Alzheimer's disease; C-reactive protein (CRP); Endothelial cells; Human brain microvessel endothelial cells (hBMECs); Systemic inflammation