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Systemic and microvascular oxidative stress induced by light chain amyloidosis. Int J Cardiol 2010 Nov 05;145(1):67-8 PMID: 19446898 PMCID: PMC2974792

Pubmed ID

19446898

DOI

10.1016/j.ijcard.2009.04.044

Abstract

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 SA

Authors

David D. Gutterman MD Sr Assoc Director, Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-78049467563   28 Citations

MESH terms used to index this publication - Major topics in bold

Aged
Amyloidosis
Arterioles
Biomarkers
Female
Humans
Immunoglobulin Light Chains
Male
Microvessels
Middle Aged
Oxidative Stress
Protein Carbonylation
jenkins-FCD Prod-331 a335b1a6d1e9c32173c9534e6f6ff51494143916