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Arteriosclerosis, Thrombosis, and Vascular Biology
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Published Online
on July 6, 2006

Arteriosclerosis, Thrombosis, and Vascular Biology. 2006
Published online before print July 6, 2006, doi: 10.1161/01.ATV.0000235720.61091.c7
A more recent version of this article appeared on September 1, 2006
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*Substance via MeSH

Submitted on April 21, 2006
Accepted on June 21, 2006

HSPA12B Is Predominantly Expressed in Endothelial Cells and Required for Angiogenesis

Rebecca J. Steagall ; Antonio E. Rusiñol ; Quynh A. Truong ; and Zhihua Han *

From the Department of Biochemistry and Molecular Biology (R.J.S., A.E.R., Z.H.), College of Medicine, East Tennessee State University, Johnson City, Tenn; and Division of Cardiology (Q.A.T.), Department of Medicine, University of California, San Francisco, Calif.

* To whom correspondence should be addressed. E-mail: han{at}etsu.edu.

Objective--HSPA12B is the newest member of HSP70 family of proteins and is enriched in atherosclerotic lesions. This study focused on HSPA12B expression in mice and its involvement in angiogenesis.

Methods and Results--The expression of HSPA12B in mice and cultured cells was studied by: (1) Northern blot; (2) in situ hybridization; (3) immunostaining with HSPA12B-specific antibodies; and (4) expressing Enhanced-Green-Fluorescent-Protein under the control of the HSPA12B promoter in mice. The function of HSPA12B was probed by an in vitro angiogenesis assay (Matrigel) and a migration assay. Interacting proteins were identified through a yeast two-hybrid screening. HSPA12B is predominantly expressed in vascular endothelium and induced during angiogenesis. In vitro angiogenesis and migration are inhibited in human umbilical vein endothelial cells in the presence of HSPA12B-neutralizing antibodies. HSPA12B interacts with multiple proteins in yeast 2-hybrid system.

Conclusions--We provide the first evidence to our knowledge that the HSPA12B is predominantly expressed in endothelial cells, required for angiogenesis, and interacts with known angiogenesis regulators. We postulate that HSPA12B provides a new mode of angiogenesis regulation and a novel therapeutic target for angiogenesis-related diseases.
Key words: angiogenesis • endothelial cells • HSPA12B • HSP70 family • migration






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