Protein Identified That Is Involved in Cardiovascular Diseases and Angiogenesis
More than 60 million Americans have one or more types of cardiovascular disease (CVD) according to current estimates. CVD claimed close to a million lives in the United States in 2001 alone, and billions of dollars are spent every year in managing these diseases. Many factors associated with CVD are still unclear.
The laboratory of Kishore Wary, Ph.D., at the Institute of Biosciences and Technology in Houston, TX, studies the biology of blood vessels (the vasculature). In particular, Wary studies the cellular behavior of endothelial cells because endothelial cells are directly responsible for the formation of new blood vessels. The formation of a new blood vessel from a parental vessel is also known as angiogenesis, which is a fundamental biological process crucial for normal and pathological developments. The study of endothelial cells is important because deregulated angiogenesis contributes to CVD, to diseases such as atherosclerosis, myocardial ischemia, stroke, thrombosis, and cardiac infarction. Angiogenesis augments rheumatoid arthritis, diabetic retinopathy, aging, psoriasis, and the growth and metastasis of tumors.
What is known is that in the adult human the endothelial cells remain dormant (they do not divide) for as long as 5-7 years. However, in response to injury and or bacterial/viral infection, the vasculature becomes inflamed, or endothelial cells become activated. Activated endothelial cells often synthesize and present a unique set of cell surface molecules that are different from dormant endothelial cell surface. Thus, identifying and characterizing such distinct molecular targets presented by the activated endothelial cells can be used to develop new diagnostic/therapeutic approaches, including substances to interfere with the growth of new blood vessels or enhance angiogenesis wherever it is required.
In Wary’s efforts to find genes and proteins that are highly expressed in newly formed vessels, his lab identified a candidate protein called Phosphatidic acid phosphatase 2b (PAP2b/VCIP) from activated endothelial cells. Serendipitously, they discovered that elevated expression of PAP2b could induce cell-to-cell interaction in cultured cells.
Dr. Wary notes, “Cell-to-cell interaction means that cells adhere to each other directly. In other words, we say these cells become very sticky or adhesive, and this was a surprising and unexpected observation. Our data is really compelling. In blood vessels, such behavior of endothelial cells could contribute to thrombosis, stroke, and recruit circulating tumor cells.” He adds, “However, PAP2b is not the only molecule that could do the job of promoting cell-to-cell interaction. There are several other known cell adhesion molecules that can do a similar job.”
Wary’s lab is now beginning to understand the biochemical mechanisms of how PAP2b induces cell-to-cell interaction, how it promotes sticky behavior. Further study will be required to understand fully how PAP2b works, and he hopes that greater mechanistic insight will provide the required clues for designing specific therapeutic substances to block unwanted thrombosis, atherosclerosis, restenosis, and tumor cell recruitment.
The study was made possible by a grant-in-aid from the American Heart Association National Council and from the Institute of Biosciences and Technology, Texas A&M University System Health Science Center new faculty start-up fund.
The Texas A&M University System Health Science Center provides the state with health education, outreach and research. Its five components located in communities throughout Texas are Baylor College of Dentistry, the College of Medicine, the Graduate School of Biomedical Sciences, the Institute of Biosciences and Technology and the School of Rural Public Health.