Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 499

9.5.8.5 Transglutaminase

Many proteins of the extracellular matrix are substrates of transglutaminase-2 (TG2)
produced by endothelial cells. Transglutaminase-2 affects both matrix deposition
and turnover. It promotes collagen-1 synthesis and resistance of the extracellular
matrix to degradation by matrix metallopeptidase MMP1, but it downregulates the
expression of collagen-3 and -4 [ 923 ].

9.5.8.6 Heparan Sulfate Proteoglycans

Different structural types of heparan sulfate are secreted on the cell surface, such
as syndecan and glypican, as well as in the basement membrane (thickness of 20-
100 nm), such as perlecan, agrin and collagen-18 [ 924 ]. 62 Several heparan sulfate
proteoglycans have heparan sulfate chains only under specific circumstances, the
part-time heparan sulfates, such as epican (CD44),

-glycan, and testican.
Heparan sulfate proteoglycans interact with manifold proteins, such as growth
factors, cytokines, chemokines, peptidases, lipases, and cell adhesion molecules.
The vascular endothelium can modulate inflammation by changing the heparan
sulfate structure, a given type of heparan sulfate being able to bind or not to a
given ligand. Heparan sulfate, in association with interacting proteins, inhibits SMC
proliferation [ 925 ].

β

9.5.8.7 Neuregulins

Neuregulins (Nrg1-Nrg4) are cell-cell signaling proteins. They are ligands of
receptor Tyr kinases of the HER family. Isotype Nrg1 63 operates in the nervous
system, heart, and breast. Neuregulin-1 possesses different isoforms from alternative
splicing of the transcript of the NRG1 gene, such as type-1 neuregulin-1, 64 type-2
neuregulin-1, or glial growth factors (GGF1-GGF3), 65 and type-3 neuregulin-1, or
sensory and motor neuron-derived factor (SMDF), in addition to type-4 to type-6
neuregulin-1.

62 These proteoglycans link to other basement membrane components, such as laminin, collagen-
4, and entactin. Five types of heparan sulfate proteoglycans always carry heparan sulfate chains,
the so-called full-time heparan sulfates. The full-time heparan sulfates on cell surfaces consist
of 4 integral-membrane syndecans and 6 glypicans, which are attached to the plasma membrane.
The 3 matrix heparan sulfate proteoglycans are perlecan, agrin, and collagen-18.
63 Neuregulin-1 isoforms are produced in various cell types, including cardiac endothelial cells.
64 A.k.a. heregulin (Hrg), NEU differentiation factor (NDF), and acetylcholine receptor-inducing
activity protein (ARIA).
65 Glial growth factors promote Schwann cell migration and proliferation.