Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

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

Pubmed ID

22981431

DOI

10.1016/j.atherosclerosis.2012.08.028

Abstract

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

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-s2.0-84867867786   12 Citations

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

Amyloidosis
Arterioles
Cell Death
Clusterin
DNA Fragmentation
Endothelial Cells
Female
Humans
Immunoglobulin Light Chains
Male
Middle Aged
Vasodilation
jenkins-FCD Prod-321 98992d628744e349846c2f62ac68f241d7e1ea70