Although all individual endothelial cells share some properties in common, the vascular endothelium taken as a whole represents a conglomerate cell system that exhibits diverse biological functions. All endothelial cells lie on the luminal surface of a vascular basement membrane, thereby forming a continuous interface between blood (or lymph) and the tissue interstitium. In this position the endothelial cell is strategically positioned to fulfill an essential bidirectional signaling role. A critical function of the vascular endothelium is the formation of a semipermeable barrier that limits bulk water and protein transport from the vascular space, while specifically trafficking particular protein molecules, such as hormones and immunoglobulins, across the barrier. Under homeostatic conditions, the endothelial cell barrier is antiadhesive but may, in response to certain chemical stimuli, become proadhesive to facilitate the directed recruitment of white blood cells to sites of injury or infection. An additional role for the vascular endothelium apart from its ability to regulate permeability is its role in regulating vascular tone and distribution of flow. Endothe-lial cells produce multiple vasoactive autocoids that regulate vascular tone moment by moment. For example, nitric oxide and prostacyclin are well-recognized vasodilators, whereas endothelin and angiotensin-converting enzyme are well-recognized vasoconstrictors. These physiologic roles, which are essential vascular functions, clearly establish that the vascular endothelium is a key regulator of homeostasis.

While endothelial cells in all vascular beds or segments share certain features in common, there is a growing recognition of their phenotypic diversity as well. For example, endothelial cells lining different organs exhibit a discernible histological structure. Endothelium that lines the blood-brain barrier, skin, muscle, and connective tissue is continuous, whereas endothelium that lines the sinusoids of the hepatic or splenic circulations, red bone marrow, adrenal and parathyroid glands, and the carotid body is not continuous. Indeed, fenestrated endothelial cells (with transcyto-plasmic vacuoles) are observed in vessels of glomeruli, some endocrine glands, pancreas, and intestinal villi. Whereas fluid readily permeates renal glomerular and liver sinusoidal endothelium, brain endothelium is nearly fluid impermeable. Similarly, striking diversity may also be found within a single organ and, in some instances, within the same vascular segment such as described by Majno and Palade [1], who observed histamine-induced intercellular gaps between the endothelial cells of postcapillary venules, but not in all immediately adjacent cells. Although the notion of heterogeneity of endothelial cells and its potential role in organ specific function is appreciated, the origins and mechanisms of heterogeneity are poorly understood.

Heterogeneity may be broadly defined as secondary diversity in a grossly "homogeneous" population. Morphological and functional cellular heterogeneity among a "homogenous" type of cell population can be related to developmental origins, anatomical and histological location, local environmental influences, and, most importantly, the pattern of gene expression. For example, in any particular cultured cell type, considerable variation is seen with regard to cellular morphology and function. Some of the variations can be attributed to different stages of cell cycle, but others may be due to a differential organization, regulation, or expression of genes (i.e., due to epigenetic controls). The study of cellular heterogeneity and its origins not only is interesting from a theoretical biological viewpoint, but also is important in predicting the fate of a cell and, consequently, its contribution to the development of disease. Individual susceptibility to a particular disease, vulnerability to particular disease risk factors, or responsiveness to a particular treatment are all factors that likely represent manifestations of cellular heterogeneity.

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Essentials of Human Physiology

Essentials of Human Physiology

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.

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