Superfund Research Program

Mechanism of Arsenic-Induced Vascular Disease

Project Leader: Aaron Barchowsky (University of Pittsburgh)
Grant Number: P42ES007373
Funding Period: 2000-2005

Project-Specific Links

Final Progress Reports

Year:   2004 

Project 1 began with the initiation of Dartmouth College’s SBRP program in 1995 as a collaboration between the late Dr. Karen Wetterhahn (Project Leader, Program Director) and Dr. Aaron Barchowsky (Co-Investigator), examining the role of oxidant signaling in the toxicological effects of arsenic, chromium and nickel.  Following Dr. Wetterhahn’s untimely death in 1997, Dr. Barchowsky took over as Project Leader for this project for the remainder of that project period, and he successfully renewed this project in 2000 with a revised set of aims more specifically focused on his laboratory’s interests in vascular and cardiovascular disease but with a continued focus on oxidant signaling.  In the current grant period Dr. Barchowsky has focused his project principally on arsenic for these effects.  In 2003, Dr. Barchowsky accepted a faculty position at the University of Pittsburgh and moved his laboratory there.  After considerable reflection and discussion, Dartmouth’s SBRP program collectively agreed that, although this project had been successful, for logistical and other reasons it would not be part of this competing renewal of the program.  However, Dr. Barchowsky plans to continue this research as part of his own program at Pittsburgh where there is considerable collective expertise in vascular, cardiovascular and pulmonary pathology. Project 1 has evolved from an interest in defining the cellular and molecular actions of metals that promote cardiovascular and pulmonary diseases.  This project has focused on mechanisms for non-malignant diseases that are linked by epidemiological studies to wide-spread human disease.  In 2000, the project focus was narrowed to examine the mechanisms for arsenic-induced vascular disease.  However, Project 1 also supported the completion of studies of gene induction by nickel in the lung.   The most significant contribution of the research in Project 1 has been the finding that acute or chronic low level arsenic exposure enhances pathological angiogenesis, the formation of new blood vessels from existing vessels.  The significance of this finding was increased by the demonstration that arsenic-induced angiogenesis enhances tumor growth (Tox Sci 76: 271-279, 2003).  This paper is first-authored by Nicole Soucy who was a Dartmouth graduate student supported by the Training Core of this program through the completion of her Ph.D. in 2003.  The work described in this paper was one of the major aims of her thesis, and this publication was unanimously voted as the best paper in Toxicological Sciences for 2003 by their editorial board.  Studies in the Barchowsky laboratory will continue to identify the cellular effects of arsenic on vascular endothelial and smooth muscle cells that translate into this important mechanism for vascular disease and tumor promotion.