Systemic and microvascular oxidative stress induced by light chain amyloidosis. Int J Cardiol 2010 Nov 05;145(1):67-8
Date
05/19/2009Pubmed ID
19446898Pubmed Central ID
PMC2974792DOI
10.1016/j.ijcard.2009.04.044Scopus ID
2-s2.0-78049467563 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
Light chain amyloidosis (AL) is a plasma cell dyscrasia associated with production of amyloidogenic immunoglobulin light chains (LC). Despite its often fatal course, the mechanism of injury remains unknown. We tested the hypothesis that AL is associated with oxidative stress by comparing serum protein carbonyl (a marker of protein oxidation and oxidative stress) in AL subjects (n=23, 60 ± 11 years) vs. controls (n=9, 54 ± 2 years); we also measured superoxide production (n=11) and dilator response to sodium nitroprusside (SNP, n=6) in isolated non-AL human adipose arterioles exposed to LC (20 μg/mL) purified from AL subjects for 1 h vs. control. Protein carbonyl was higher in AL patients (0.19 ± 0.04 vs. 0.003 ± 0.003 nmol/mg control, p=0.002). Post-exposure to LC proteins, arteriole superoxide was higher (1.89 ± 0.36 times control, p=0.03) with impaired dilation to SNP (10(-4) M, 54 ± 6 vs. 86 ± 4%, p=0.01, logEC50 -3.7 ± 0.2 vs. -6.7 ± 0.6, p=0.002). AL is associated with systemic oxidative stress and brief acute exposure to AL light chain proteins induces oxidative stress and microvascular dysfunction in human adipose arterioles. This novel mechanism of injury may be important in AL pathophysiology.
Author List
Migrino RQ, Hari P, Gutterman DD, Bright M, Truran S, Schlundt B, Phillips SAAuthor
Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedAmyloidosis
Arterioles
Biomarkers
Female
Humans
Immunoglobulin Light Chains
Male
Microvessels
Middle Aged
Oxidative Stress
Protein Carbonylation
