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Protective role of clusterin in preserving endothelial function in AL amyloidosis. Atherosclerosis 2012 Nov;225(1):220-3 PMID: 22981431 PMCID: PMC3478430

Pubmed ID



UNLABELLED: Misfolded immunoglobulin light chain proteins (LC) in light chain amyloidosis (AL) are toxic to vascular tissues. We tested the hypothesis that chaperone protein clusterin preserves endothelial function and cell survival during LC exposure.

METHODS: LC (20 μg/mL) were given to human aortic endothelial cells (EC) for 24-h and clusterin protein/gene expression and secretion were measured. DNA fragmentation was measured with/without recombinant clusterin (Clu, 300 ng/mL). Adipose arterioles (non-AL subjects) were tested for dilator responses to acetylcholine/papaverine at baseline and after 1-h of LC ± Clu.

RESULTS: LC reduced EC clusterin secretion, protein and gene expression while increasing DNA fragmentation. Clu attenuated LC-induced DNA fragmentation and restored dilator response to acetylcholine (logEC50: control -7.05 ± 0.2, LC + Clu -6.53 ± 0.4, LC -4.28 ± 0.7, p < 0.05 versus control, LC + Clu).

CONCLUSIONS: LC induced endothelial cell death and dysfunction while reducing clusterin protein/gene expression and secretion. Exogenous clusterin attenuated LC toxicity. This represents a new pathobiologic mechanism and therapeutic target for AL amyloidosis.

Author List

Franco DA, Truran S, Burciu C, Gutterman DD, Maltagliati A, Weissig V, Hari P, Migrino RQ


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


2-s2.0-84867867786   12 Citations

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

Cell Death
DNA Fragmentation
Endothelial Cells
Immunoglobulin Light Chains
Middle Aged
jenkins-FCD Prod-300 626508253d14e4184314fb9f66322a03a5906796