Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 474

vasoactive metabolites such as 15-hydroxy (11,12)-epoxyeicosatrienoic acid that
is hydrolyzed by soluble epoxide hydrolase to (11,12,15)-trihydroxyeicosatrienoic
acid. Hydroxyepoxy- and trihydroxyeicosatrienoic acids are endothelium-derived
hyperpolarizing factors that activate calcium-activated, small-conductance K Ca 2
channels [ 825 ]. In vascular endothelium of other arteries, arachidonate 12-
lipoxygenase (ALOx12) produces 12-hydroxyeicosatetraenoic acid that relaxes
smooth myocytes via calcium-activated, large-conductance K Ca 1 channel [ 825 ].
Insulin activates the PI3K pathway not only to stimulate glucose uptake, but
also to promote synthesis of nitric oxide in the endothelium. Insulin hence favors
endothelium-dependent relaxation of vascular smooth myocytes (Sect. 9.10 ).

9.5.1 Caveolae

Caveolae are specialized, invaginated membrane rafts, i.e., dynamic assemblies of
sphingolipids and cholesterol, that contribute to vesicular transport and signaling.
They indeed concentrate or segregate receptors and signaling intermediates. These
nanodomains constitute platforms on which kinases and phosphatases can operate.
Caveola-mediated endocytosis differs from other types of endocytosis by chemical
sensitivities, cargos, adaptors, and signaling proteins (Vol. 1 - Chap. 9. Intracellular
Transport).
The organization and function of caveolae depend on coat caveolins and adaptor
cavins (cavin-1-cavin-4) that promote membrane remodeling and caveolin-derived
structure transfer. Caveolae can form transendothelial channels and vesiculovacuo-
lar organelles and cavicles.
Caveolin-1 and -2 lodge in most cell types of the cardiovascular apparatus,
whereas Cav3 is expressed primarily in myocytes (cardiac, skeletal, and smooth
myocytes). Caveolin-1 or -3 is needed for the formation of caveolae, but not Cav2.
Caveolin-1 resides in the plasma membrane and Golgi body. Exocytosis from
the Golgi body to the plasma membrane is regulated by amyloid- protein and

insulin [ 878 ]. In addition, Cav1 endocytosis is controlled by Na + -K + AT P a s e .
Caveolin-2 supports caveola assembly via its hetero-oligomerization with Cav1.

β

9.5.1.1 Regulators of Caveolae

Cavins (cavin-1-cavin-4) regulate caveolin density as well as caveola morphol-
ogy [ 878 ]. 28

Cavins possess leucine zipper-like domains for between-protein

28 Cavin-1 is also known as polymerase transcript release factor (PTRF); cavin-2 serum deprivation
protein response (SDPR); cavin-3 as protein kinase-C δ -binding protein (PKC δ BP) and serum
deprivation response-related gene product (SDPR) that binds to C-kinase (SRBC); and cavin-4
as muscle-restricted coiled-coil protein (MURC).