During the past few years, the cellular mechanisms regulating microvascular morphogenesis have come under close scrutiny. In consideration of the important role that cell-to-cell and cell-to-matrix interactions play in regulating these developmental and disease-related processes, researchers have taken advantage of the technology and approaches founded in genetics and cell biology in their efforts aimed at revealing the molecular mechanisms controlling developmental and pathologic angiogenesis. Although significant inroads have been made with regard to the molecular and cellular details that govern endothelial seeding of early organ primordia or the regulatory role that pericytes play in microvascular physiology, there is currently little knowledge regarding the molecular and cellular events regulating vascular morphogenesis, including the signals regulating the recruitment and local differentiation of pericytes. Presumably, the early inductive events that stimulate vascular endothelial growth are also linked to the subsequent rounds of vascular remodeling seen in association with vascular proliferative disorders (e.g., tumor-induced angiogenesis, diabetic retinopathy, age-related macular degeneration). Collectively, these vascular morphogenetic events are characterized by the (1) growth/differentiation of vascular endothelial cells, (2) subsequent immigration and/or colonization of microvessels with pericytes, and (3) incipient dedifferentiation, loss, or death of pericytes that initiates or sustains the vascular pathophysiologic state. Based on our work and experiments carried out in our colleagues' labs, it seems quite likely that pericyte growth and differentiation are critically dependent on autocrine signals, cues that emanate from the microvascular endothelium and informa tion arising from the associating extracellular matrix components present in the capillary basement membrane. In turn, these homotypic and heterotypic cellular interactions (i.e., endothelial-endothelial, endothelial cell-pericyte, and pericyte-astrocyte) and the interactions that occur between these cells and the surrounding extracellular matrix dictate where, when, and how vascular cell growth and differentiation ensue. Moreover, acute or chronic perturbations in these molecular and cellular signaling pathways will play pivotal roles in developmental or pathologic angiogenesis.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.