Myoendothelial Contacts, Gap Junctions, and Microdomains: Anatomical Links to Function?

Abstract

In several species and in many vascular beds, ultrastructural studies describe close contact sites between the endothelium and smooth muscle of <∼20nm. Such sites are thought to facilitate the local action of signaling molecules and/or the passage of current, as metabolic and electrical coupling conduits between the arterial endothelium and smooth muscle. These sites have the potential for bidirectional communication between the endothelium and smooth muscle, as a key pathway for coordinating vascular function. The aim of this brief review is to summarize the literature on the ultrastructural anatomy and distribution of key components of MECC sites in arteries. In addition to their traditional role of facilitating electrical coupling between the two cell layers, data on the role of MECC sites in arteries, as signaling microdomains involving a spatial localization of channels, receptors and calcium stores are highlighted. Diversity in the density and specific characteristics of MECC sites as signaling microdomains suggests considerable potential for functional diversity within and between arteries in health and disease.

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

“…Within the connexin isoforms expressed in the vasculature, heteromeric channels have been identified for Cx37/Cx40 (Ayad et al, 2006;Laird, 2006;Smith et al, 2012), Cx37/Cx43 (Brink et al, 1997;Larson et al, 2000;Wang et al, 2005;Beyer et al, 2013), Cx40/ 43 (He et al, 1999;Stergiopoulos et al, 1999;Bouvier et al, 2009), Cx40/Cx45 (Martinez et al, 2002); Cx43/ Cx45 (Moreno et al, 1991;Koval et al, 1995), and Cx43: Cx32 (Lagree et al, 2003;Vanslyke et al, 2009). Typically, compared with homomeric hemichannels, these heteromeric associations produce channels with altered gating sensitivities to voltage, pH, or Ca 2+ ; altered channel opening; different ion selectivity; and (Sandow et al, 2012). 536 permeability properties, but their membrane targeting is not altered (Beyer et al, , 2001Cottrell and Burt, 2001;Wei et al, 2004).…”

Endothelial and Smooth Muscle Cell Interactions in the Pathobiology of Pulmonary Hypertension

“…Currently, three different connexins (Cx 37, 40, and 43) are known to be associated with the MEJ that allow the transfer of current and small molecules (,z1.2 kD) between the cytoplasm of these adjacent cells (14). MEJs have been observed in several species and in many vascular beds, including the pulmonary vasculature (13,(90)(91)(92). There are more numerous MEJs in smaller-than in larger-diameter arteries (10,13,93).…”

“…MEJs have been observed in several species and in many vascular beds, including the pulmonary vasculature (13,(90)(91)(92). There are more numerous MEJs in smaller-than in larger-diameter arteries (10,13,93). The more abundant expression of MEJs would facilitate electronic signals propagating between EC and SMC.…”

“…13,95). For a particular blood vessel, the MEJ may be derived from the EC, from the SMC, or from both cell types and may meet halfway between them, as observed in canine pulmonary arteries and veins (13,90).…”

“…However, there is increasing evidence that the relationship between the EC and the SMC is not a simple one-way interaction from the endothelium to the SMC; rather, there are complicated interactions between them (9-11). Moreover, the communication patterns are not limited to paracrine signaling; cross-talk through myoendothelial gap junctions (MEJs), extracellular vesicles (EVs), and other mechanisms is critically involved (12)(13)(14)(15)(16)(17)(18)(19)(20). These mechanisms operate in a complicated but co-ordinated manner to maintain the homeostasis of the pulmonary circulation.…”