Systemic and microvascular oxidative stress induced by light chain amyloidosis.
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.
Migrino
Raymond Q
RQ
Hari
Parameswaran
P
Gutterman
David D
DD
Bright
Megan
M
Truran
Seth
S
Schlundt
Brittany
B
Phillips
Shane A
SA
D000368:Aged; D000686:Amyloidosis / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D001160:Arterioles / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000009:adverse effects* / Q000096:biosynthesis / Q000097:blood; D008297:Male; D055806:Microvessels / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D018384:Oxidative Stress / Q000276:immunology*; D050050:Protein Carbonylation / Q000276:immunology
D015415:Biomarkers; D007147:Immunoglobulin Light Chains