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Endocardial Endothelial Modulation of Myocardial Contraction
Published in Malcolm J. Lewis, Ajay M. Shah, Endothelial Modulation of Cardiac Function, 2020
Stanislas U. Sys, Puneet Mohan, Luc J. Andries, Gilles De Keulenaer, Paul F. Fransen, Dirk L. Brutsaert
The EE cells have extensive intercellular overlapping (Figure 1-2) and the intercellular clefts between EE cells are significantly longer than between coronary capillary endothelial cells (Andries, 1994). One or two junctional points, tight junctions, obliterating the intercellular cleft have been seen in rat and cat. Tight junctions act as a selective barrier to small molecules and as a total barrier to large molecules. The tight junction permeability is modulated by the peripheral actin band present in EE cells. Gap junctions, sites of low electrical resistance between adjacent cells, are present between EE cells and are prominent in junctional areas with extensive overlap (Anversa, Giacomeli and Wiener, 1975). The presence of gap junctions suggests electrochemical coupling of EE cells whereby second messengers released by activation of a single EE cell could traverse gap junctions and activate neighbouring EE cells and thus amplify the release of endothelial factors.
Endothelium
Published in Neil Herring, David J. Paterson, Levick's Introduction to Cardiovascular Physiology, 2018
Neil Herring, David J. Paterson
Water and small, lipid-insoluble solutes, such as glucose, amino acids and drugs, can cross the endothelial barrier via the intercellular clefts, chiefly in capillaries. The clefts are 20 nm wide and occupy only 0.2%-0.4% of the capillary surface (Figure 9.2, top). Rows of protein particles in the cell membrane facing the cleft form junctional strands. Two or three junctional strands run around the cell perimeter. The strands on neighbouring cells meet across the intercellular cleft to form tight junctions (Figure 9.3). However, the tight junctions do not continue unbroken around the entire cell perimeter; there are occasional 150-200 nm long breaks in the junctional strands, which provide a continuous, albeit tortuous, permeable pathway across the capillary wall (Figures 9.4 and 10.3). The number and width of the breaks greatly influence capillary permeability; postcapillary venules, for example, have fewer junctional strands and wider breaks than capillaries, so they have a higher permeability to water; whereas brain capillaries have numerous, complex junctional strands with no breaks, so their permeability is very low.
Basic physiology of the blood-brain barrier in health and disease: a brief overview
Published in Tissue Barriers, 2021
The intercellular cleft between adjacent endothelial cells of brain capillaries houses two major types of junctional complex; TJs and adherence junctions (Figure 5Figure 6Figure 7). Tight junctions are highly dynamic structures that effectively limit the movement of water and solutes and regulate lateral diffusion through the paracellular pathway.22,23,119,120 These structures are formed by transmembrane proteins claudins, occludin, and junctional adhesion molecules (JAMs) which interact with the actin cytoskeleton of the endothelial cells by a number of cytoplasmic accessory proteins including ZO proteins, cingulin, AF-6, and 7H6.22,121–124 The interaction between ZO proteins and transmembrane proteins, including claudins and occludin have been shown to determine the stability and function of TJs.22,125–127 In contrast to the epithelial cells which exhibit intercellular gaps sealed by TJs localized at the most apical point of cellular attachment immediately above the clearly distinguishable adherens junctions, barrier type endothelial cells in the brain are joined together by TJs and adherens junctions showing more variable localizations and intermingled appearances.128
Lipid-based nanoformulations in the treatment of neurological disorders
Published in Drug Metabolism Reviews, 2020
Faheem Hyder Pottoo, Shrestha Sharma, Md. Noushad Javed, Md. Abul Barkat, Md. Sabir Alam, Mohd. Javed Naim, Ozair Alam, Mohammad Azam Ansari, George E. Barreto, Ghulam Md. Ashraf
BBB is a peculiar membranous barricade that firmly segregates the brain from blood circulation (Omidi and Barar 2012). Due to its ubiquitous features, movement of ions and molecules is restricted. It consists of endothelial cells, astroglia, pericytes, and perivascular mast cells that prevent the movement of the circulating cells and molecules (Schlosshauer and Steuer 2002; Daneman and Prat 2015; Nigar et al. 2016). In the brain, the interchange of molecules occurs transcellularly, while capillaries, intercellular cleft, and fenestrae are nonexistent (Bodor and Buchwald 1999). Hence, only lipid-soluble solutes can transverse across the capillary endothelial membrane, while polar or aqueous compounds, ions are practically impermeable. As a result, low concentration of drugs (hydrophilic) reaches neuronal tissues with a reduction in their therapeutic efficacy (Misra et al. 2003). The tightness of the BBB is ascribed chiefly due to a vascular layer of brain capillary endothelial cells, linked with each other by tight and adherens junctions. The tight junctions mainly accomplish two functions. Firstly they prohibit the entry of smaller molecules and ions through the space present between cells; therefore, the passage mainly occurs by active transport (Zhong et al. 2017). Secondly, they inhibit the passage of the integral membranous proteins among the apical and basolateral membranes of the cell thus preserving the important functions of the cell membrane that includes receptor-mediated endocytosis and exocytosis.
Cell-cell junctions: structure and regulation in physiology and pathology
Published in Tissue Barriers, 2021
Mir S. Adil, S. Priya Narayanan, Payaningal R. Somanath
TJs are characterized as a set of continuous and anastomosing strands at the apical-most regions of the lateral cell membranes seal the paracellular spaces.25 AJs play an important role in contact inhibition of EC22 and EpC growth,26 a phenomenon wherein cells stop growing further when bordered by other cells thereby forming a confluent ‘cobblestone’ monolayer of polygonal cells.27 Contact inhibition in confluent cell cultures is a dramatic decrease in cell mobility and mitotic rate with increasing cell density. The stationary post-confluent layer established is insensitive to nutrient renewal.28 In EpCs, junctions are better organized, with TJ and AJ following a well-defined spatial distribution along the intercellular cleft. While the TJs (or zonula occludens) are concentrated at the apical side of the rim, the AJs (or zonula adherens) are located below the TJ. Unlike EpCs, ECs reveal a less defined junctional architecture wherein AJs are intermixed with TJs along the cleft.22 Moreover, TJs of endothelial sheets in vivo are leaky in general, since a wide variety of substances must be exchanged between the blood and organs through the paracellular as well as transcellular routes.25 Even though ECs and EpCs share numerous TJ components, the same molecules might be differentially assembled and regulated in the two cell types. Further, there is a substantial variability among different segments of the vascular tree. Particularly, in large vessels, TJs are well developed in arteries and less sophisticated in veins.22 When it comes to small vessels, these junctions are well organized in arterioles, but loosely organized (even with some gaps) in venules, a preferential site for the extravasation of plasma proteins and circulating leukocytes. Finally, brain vessels that contribute to the blood-brain barrier (BBB) have well developed TJs compared to other organs characterized by high rate trafficking.22