2 results
36 - Thrombospondins
- from PART II - ENDOTHELIAL CELL AS INPUT-OUTPUT DEVICE
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- By Sareh Parangi, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, Jack Lawler, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
- Edited by William C. Aird, Harvard University, Massachusetts
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- Book:
- Endothelial Biomedicine
- Published online:
- 04 May 2010
- Print publication:
- 03 September 2007, pp 324-336
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Summary
The thrombospondins (TSPs) are a family of proteins that regulate cellular phenotype and matrix structure during tissue remodeling and genesis (1,2). Of the five proteins that comprise the family, TSP-1 and -2 have been shown to be involved in vascular development and angiogenesis (3,4). The endothelial cell (EC) integrates positive and negative signals for proliferation, migration, survival, and apoptosis during physiological and pathological angiogenesis. TSP-1 and -2 suppress the angiogenic response by inhibiting migration and antagonizing vascular endothelial growth factor (VEGF)-induced survival. In addition, TSP-1 and -2 stimulate apoptotic pathways in ECs (5). The importance of TSP-1 as a negative regulator of angiogenesis is underscored by the fact that genetic mutations that occur in tumor cells often lead to reduced TSP-1 expression (2). Furthermore, a TSP-1–based therapeutic is currently in clinical trials for the treatment of cancer. Although generally an inhibitor of angiogenesis, TSP-1 has been shown to support angiogenesis in some contexts. This seemingly paradoxical effect stems from the fact that various cell types respond differently to the protein. Whereas TSP-1 inhibits EC migration, it supports vascular smooth muscle cell (VSMC) and inflammatory cell migration. Thus, if the induction of angiogenesis occurs in the presence of inflammation, TSP-1 can appear to promote angiogenesis. In addition, the N-terminal heparin-binding domain of TSP-1 assayed in isolation reportedly stimulates angiogenesis (6). These complex responses arise because TSP-1 and -2 are multifunctional proteins with a wide range of cell surface receptors. The cellular response to these proteins in part depends on which receptors are expressed by a given cell type and which receptors are engaged by the various domains of TSP-1 or -2.
151 - The Role of the Endothelium in Normal and Pathologic Thyroid Function
- from PART III - VASCULAR BED/ORGAN STRUCTURE AND FUNCTION IN HEALTH AND DISEASE
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- By Jamie Mitchell, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, Anthony Hollenberg, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, Sareh Parangi, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
- Edited by William C. Aird, Harvard University, Massachusetts
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- Book:
- Endothelial Biomedicine
- Published online:
- 04 May 2010
- Print publication:
- 03 September 2007, pp 1386-1396
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- Chapter
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Summary
Angiogenesis, the formation of new blood vessels from existing vessels, has been recognized as playing an important role in the pathophysiology of many benign and malignant diseases (1,2). This chapter focuses on the role of the endothelium in the thyroid gland and explores the advances that have been made in our understanding of how the process of angiogenesis is involved in the pathophysiology of benign and malignant diseases of this gland.
HISTORY OF ENDOTHELIAL BIOLOGY IN THE THYROID
The structure and function of the thyroid gland has been the intense focus of study by physiologists, anatomists, surgeons, and basic scientists. Most attention has focused on the thyroid follicular cell, one of the most thoroughly studied cells in the human body. By comparison, the thyroid endothelium has received little attention. In the mid 1970s, there was increasing recognition that the endothelium of endocrine organs, including the thyroid, played an important role in homeostasis. At first, microscopy was used to study the structural detail of the fenestrated endothelium present in normal rat thyroid (3) as well as benign and malignant human thyroid tissue (4). The importance of angiogenesis in the progression of malignant disease was recognized during the early 1970s, with the realization by Folkman and colleagues that, for malignant tumor growth to progress beyond approximately 2 mm in diameter, the development of a vascular supply must occur (5). The role of endothelial cell (EC) proliferation in thyroid disorders was appreciated as early as 1978, with work performed by Wollman and colleagues (6).