The vascular endothelium: a survey of some newly evolving biochemical and physiological features

Summary

The morphological, biochemical and functional characterization of the vascular endothelium has become possible through the broad use of electron microscopic methods, the successful elaboration and application of techniques for the isolation and cultivation of endothelial cells in vitro and through sophisticated studies on vessel and organ preparations, both in vitro and in vivo. In this survey emphasis is placed on certain methodological aspects of endothelial cell culture as well as on biochemical, physiological and pathophysiological features of the vascular endothelium.

Endothelial cells can be propagated in culture dishes, the most commonly applied method, on suspended microbeads (dextrane, polyacrylamide), a technique giving large yields, or on thin porous membranes, a procedure suited for the study of transport processes across the endothelial layer.

Different structural, biochemical and functional properties of the luminal (apical) and abluminal (basal) cell membrane determine important polarity features of the endothelium. Endothelial cells exhibit a variety of biochemical pathways and are characterized by high metabolic activities. Of particular interest is the large content of ATP in endothelial cells of different vascular origin. The rapid intracellular degradation of adenine nucleotides to nucleosides and bases, which are constantly released, is balanced by synthesis, mainly via salvage pathways. In endothelial cells of microvascular origin uric acid predominates by far as the final purine degradative because of the presence of xanthine dehydrogenase in these cells; in the macrovascular endothelium purine breakdown proceeds only to hypoxanthine, since xanthine dehydrogenase is lacking. In this connection interrelations between nucleotide catabolism in myocardial tissue and in coronary endothelial cells are discussed, also with respect to the participation of endothelial xanthine oxidase in the formation of oxygen radicals during post-ischemic reperfusion of the heart.

Vascular endothelial cells of different origin are also capable of a rapid extracellular degradation of ATP, ADP and AMP to adenosine by means of specific ecto-nucleotidases. The subsequent fate of extracellularly formed adenosine appears to be different for endothelial cells of microvascular (preferential adenosine uptake) and macrovascular origin (preferential extracellular adenosine accumulation), thus implying functional consequences for platelet aggregation.

Experimentally well supported aspects of endothelial functions under physiological and pathophysiological conditions include:

• - the involvement of metabolic properties of the endothelium in the separation of the intra-and extravascular space (barrier function, e.g. intraendothelial trapping of adenosine, active participation in leukocyte emigration);

• - the facilitation of CO₂-release in the lung (endothelial carboanhydrases);

• - the participation in the regulation of vascular resistance (formation of angiotensin II and degradation of bradykinin by means of angiotensin converting enzyme, formation of not yet identified endothelium derived relaxing factor(s) [EDRF] in response to various intraluminally present vasodilating substances);

• - the establishment of an antithrombogenic luminal surface of the vessel wall (release of PGI₂-adenosine, antithrombin III and plasminogen activator, intravascular degradation of adenine nucleotides to adenosine by endothelial ecto-nucleotidases, activation of protein C by endothelial thrombomodulin, heparan and antithrombin III containing endothelial glycocalyx).