Pericytes in the macrovascular intima: possible physiological and pathogenetic impact

Abstract

The frequently observed de-endothelialization of venous coronary bypass grafts prepared using standard methods exposes subendothelial prothrombotic cells to blood components, thus endangering patients by inducing acute thromboembolic infarction or long-term proliferative stenosis. Our aim was to gain deeper histological and physiological insight into these relations. An intricate network of subendothelial cells, characterized by histological features specific for true pericytes, was detected even in healthy vessels and forms, coupled to the luminal endothelium, a second leaflet of the macrovascular intima. These cells, and particularly those in the venous intima, express enormous concentrations of tissue factor and can recruit additional amounts of up to the 25-fold concentration within 1 h during preincubation with serum (intimal pericytes of venous origin activate 30.71 ± 4.07 pmol coagulation factor x·min−1·10−6 cells; n = 15). Moreover, decoupled from the endothelium, they proliferate rapidly (generation time, 15 ± 2.1 h, n = 8). Central regions of atherosclerotic plaques, as well as of those of restenosed areas of coronary vein grafts, consist almost completely of these cells. In stark contrast with the prothrombogenicity of the intimal pericytes, intact luminal endothelium recruits high concentrations of thrombomodulin (CD 141) specifically within its intercellular junctions, activates Protein C rapidly (42 ± 5.1 pmol/min·106 venous endothelial cells at thrombin saturation; n = 15), can thus actively prevent coagulatory processes, and never expresses histologically detectable and functionally active tissue factor. Given this strongly prothrombotic potential of the intimal pericytes and their overshooting growth behavior in endothelium-denuded vascular regions, they may play important roles in the development of atherosclerosis, thrombosis, and saphenous vein graft disease.

Wall structures of myocardial precapillary arterioles and postcapillary venules reexamined and reconstructed in vitro for studies on barrier functions

“…initially in the larger and smaller arteries, was that AP was not expressed in the media but selectively in the subendothelial cell layer of the arterial intima. This was of particular interest in view of our recent finding of a subendothelial cell population (subsequently identified as pericytes) constitutively present in the intima of human aorta and healthy large human veins (32). There, however, AP was expressed only when endothelial damage exposed these cells to serum.…”

“…50a), deposited on the abluminal surface of cocultured EC, leading to the recurring, but erroneous, belief that AP is an endothelial marker (20,43,57). In this respect, the arteriolar pericytes resembled those in the subendothelium of the aorta and of large human veins after their activation (32). Membrane-bound enzymes such as AP may be released from cells in forms that retain the lipid components that mediate their anchorage within membranes.…”

“…Since direct contact between the EC and pericytes through filter pores during the establishment of the sandwich cultures (during 1 wk) could definitely be excluded (we dealt with unstimulated cells and the ECM of the pericytes prevented apparently the penetration of pericyte processes at least in the routinely prepared sandwich cultures), the mutual influence exerted by these cell types in the sandwich cultures on each other's degree of differentiation is mediated by release products. Indeed, we showed recently that luminal EC and the coordinated subendothelial pericytes in the intima of large human veins exert a strong mutual influence on each other with respect to growth and proliferation (32), if they were cocultured in the sandwich manner.…”

Vascular Wall Progenitor Cells in Health and Disease

“…However, the authors also concluded that cell migration more than proliferation contributed to neointimal hyperplasia. Although early reports indicated that adventitial fibroblasts were the probable candidate for this migratory phenomenon, 64 subsequent studies have largely rejected this notion on the way to demonstrating roles for adventitial SPCs, 5,62 medial MVSCs, 7 and intimal and adventitial pericytes 134,135 in mediating neointimal thickening. The mechanisms by which adventitial VW-PCs are released from their niches and migrate to the other mural layers are far from resolved.…”

Cell-Cell Interactions and Cross Talk Described in Normal and Disease Conditions: Morphological Approach

“…Motegi, et al [46] studied the role of Pericyte-Derived MFG-E8 Regulates Pathologic Angiogenesis. Recent interest in pericytes also stems from their potential involvement in diseases [43][44][45][46][47] such as diabetic microangiopathy [48,49] tissue fibrosis [50] cancer [51] atherosclerosis [52] and Alzheimer''s disease [53,54].…”