Organotypic vasculature: from descriptive heterogeneity to functional pathophysiology

HG Augustin, GY Koh - Science, 2017 - science.org
Science, 2017science.org
BACKGROUND Each organ in the human body has its own capillary bed to carry out its
distinctive and versatile functions in response to dynamically changing systemic and local
needs. Common and specific functions of the microvasculature in different organs are
executed by organ-specifically differentiated endothelial cells (ECs). The morphological
differentiation of ECs into barrier-forming continuous ECs, fenestrated ECs, and sinusoidal
ECs has long been recognized. Nevertheless, the functional properties and underlying …
BACKGROUND
Each organ in the human body has its own capillary bed to carry out its distinctive and versatile functions in response to dynamically changing systemic and local needs. Common and specific functions of the microvasculature in different organs are executed by organ-specifically differentiated endothelial cells (ECs). The morphological differentiation of ECs into barrier-forming continuous ECs, fenestrated ECs, and sinusoidal ECs has long been recognized. Nevertheless, the functional properties and underlying molecular mechanisms of organotypic vasculatures have only been uncovered recently.
ADVANCES
This Review covers recent advances in the biology of organotypically differentiated microvascular beds. It describes the key features of continuous, discontinuous, and sinusoidal ECs, as well as the more specialized ECs of Schlemm’s canal and high endothelial venules. Major transcriptional pathways of EC specification and differentiation are outlined, including GATA4 as a key transcription factor of sinusoidal EC differentiation. The molecular shear stress–sensing machinery—which transduces blood flow–mediated biophysical forces that are essential to maintain the quiescent, differentiated EC phenotype—is delineated.
In terms of function, this Review also discusses discoveries in different organs, including liver, lung, and bone, that have identified organotypically differentiated ECs as a source of paracrine (“angiocrine”)–acting cytokines, through which they exert active gatekeeper roles on their microenvironment. ECs thereby control organ development, homeostasis, and tissue regeneration.
On the basis of these general principles of organotypic vascular differentiation and function, this Review comprehensively covers recent landmark discoveries pertaining to the organotypically specialized (micro)vasculature in different organs. Focusing on the molecular structure-function analysis of organotypically differentiated (micro)vasculatures, it specifically highlights the properties of blood vessels in the brain, eyes, heart, lungs, liver, kidneys, bones, adipose tissue, and endocrine glands. Emphasis is given to the contribution of organotypically differentiated vasculatures to both physiological organ function and disease.
OUTLOOK
Research into the mechanisms of organotypic vascular differentiation and function has emerged in recent years as a new branch of vascular biology, with major implications for our understanding of physiological and pathophysiological organ function. Ongoing research is aimed at deciphering, in much higher resolution (all the way to the single-cell level), the molecular microarchitecture of organotypic vasculatures, understanding the multicellular cross-talk through which organotypic vasculatures control their microenvironment, dissecting niche functions of organotypic vasculatures with respect to stem cells and their progeny, and unraveling the fate maps of different organotypic vasculatures in health and disease. Future research will not only focus on deciphering the molecular mechanisms and functional consequences of organotypic vascular differentiation, but will also aim to translate such knowledge for the development of novel organ- and vessel bed–specific angiotargeted therapies for multiple diseases that have hitherto been intractable.
Organotypically differentiated vasculatures take center stage in vascular biology research.
Blood vessels in the body (clockwise from top left, vessels in the brain, retina, heart, adrenal gland, bone, and liver) come in different morphologies and have distinct organotypic characteristics that enable them to execute vessel bed–specific functions. They thereby act as …
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