Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 495

mitochondrial aldehyde oxidase, and cytochrome-C, as well as bacteria, in different
tissues under different conditions [ 912 , 913 ]. Hemoglobin operates at normal pH
and oxygen saturation in the vasculature.

Hydrogen Sulfide

Hydrogen sulfide (H 2 S) is a smooth myocyte relaxant. Whereas cystathionine -

lyase is the major H 2 S-producing enzyme in smooth myocytes, 3-mercaptopyruvate
sulfurtransferase (3MST) and cysteine aminotransferase (CAT) synthesize H 2 S
from cysteine and

γ

α -ketoglutarate in vascular endothelial cells [ 914 ].

9.5.6 Adhesion Molecules

Platelet-endothelial cell adhesion molecule PECAM1, 52 an inhibitory receptor,
contains an intracellular C-terminus with 2 immunotyrosine-based inhibitory motifs
(ITIM) that launch inhibitory signaling upon transhomophilic engagement in inter-
cellular interaction (CD31

cell adhesion). Its extracellular motifs are
also required for signaling [ 915 ]. Molecule PECAM1 participates in the regulation
of angiogenesis and prevents leukocyte-endothelial cell adhesion and activation
of platelets and T lymphocytes. Once PECAM1 is eliminated after cleavage and
secretion, inflammation can occur. A truncated extracellular PECAM1 fragment
on T lymphocyte surface cannot preclude inflammation, but a PECAM1-derived
peptide is able to stimulate this fragment, thereby restoring the PECAM1 inhibitory
pathway, thereby repressing inflammation and suppressing atherosclerosis and
aneurysm evolution [ 916 ]. Molecule PECAM1 primes phosphorylation of PTPn11
phosphatase in activated leukocytes.
In given environments, cells may express different forms of PECAM1 that exert
different functions. For example, it loses its intercellular junction role when en-
dothelial cells are exposed to inflammatory cytokines [ 915 ]. In addition, neutrophils
can lose PECAM1 surface expression after extravasation.
Oxidized low-density lipoprotein (oxLDL) is an autoantigen that reduces the
existence of extracellular PECAM1 and increases the presence of its soluble
form in cultures of CD4

+ cell-CD31 +

T lymphocytes [ 915 ]. In atherosclerotic plaques and
tissues surrounding aneurysmal aortas, macrophages have an attenuated activity
with reduced production of intracellular peptidases and release of cytokines and
chemokines.

+

52 Initially identified on endothelial cells and platelets, PECAM1 also lodges on blood leukocytes
(granulocytes, monocytes, and a lymphocyte subset.