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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2012.)
© 2006 American Heart Association, Inc.

Vascular Biology

HSPA12B Is Predominantly Expressed in Endothelial Cells and Required for Angiogenesis

Rebecca J. Steagall; Antonio E. Rusiñol; Quynh A. Truong; 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.

Correspondence to Zhihua Han, East Tennessee State University, College of Medicine, Johnson City, TN 37614. 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.

We characterized the HSPA12B expression in mice and HSPA12B involvement in angiogenesis. Uniquely among HSP70s, HSPA12B is expressed predominantly in vascular endothelium, induced during angiogenesis, and essential for angiogenesis and cell migration. HSPA12B interacts with multiple proteins in a yeast 2-hybrid screening. HSPA12B is the first characterized endothelium-specific chaperone.

Key Words: angiogenesis • endothelial cells • HSPA12B • HSP70 family • migration