Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 595

Table 9.32. Plasmalemmal transducers of stresses applied by flowing blood to cells of the
vessel wall (endothelial and smooth muscle cells; AKAP: A-kinase anchoring protein; ERK:
extracellular signal-regulated protein kinase; ET: endothelin; FAK: focal adhesion kinase; IKK:
inhibitor of NF B kinase; KLF: Kruppel-like factor; MAPK: mitogen-activated protein kinase;

NADPH oxidase: reduced form of nicotinamide adenine dinucleotide phosphate oxidases; NF

κ

κ B:

nuclear factor light-chain enhancer of activated B cells; NO: nitric oxide; PECAM: platelet

endothelial cell adhesion molecule; PI3K: phosphatidylinositol 3-kinase; PK: protein kinase;
PTPn: protein Tyr phosphatase non-receptor; RTK: receptor Tyr kinase; SHC: Src-homologous
and collagen-like substrate; VEGFR: vascular endothelial growth factor receptor).

κ

Transducer Pathway

G proteins PKC-ET, ERK

RTK PI3K, MAPK

Ca 2 + channels

NO

K + channels PKA/C-AKAP-SAP-FAK2

NADP oxydase ERK

Cadherin-5 PI3K-PKB (VEGFR2, β -catenin, PTPn11)

PECAM1 ERK; NK κ B; PI3K (VEGFR2)

Integrin Rho-cytoskeleton; VEGFR2 (SHC); IKK-NK κ B

Caveolin NOS; receptors

Occludin Cell junction

KLF2 NO, ET, adrenomedullin

Table 9.33. Time scales of cell responses to hemodynamic stresses.

Event Time scale

Stress-activated ion channel

O (ms)

Ca 2 + ] i

[ O (s)

NO O (ms)

IP 3 O (10 s)

Adenylate cyclase O (mn)

PGI2, PGF2 α O (mn)

PDGF, ET, tPA hours

Cell proliferation hours

Cytoskeleton alignment hours

LDL metabolism day

Cell alignment day

Cell growth days

Secondarily, but only after a short delay, vascular endothelial cells can release nitric
oxide, among other vasoactive substances, that targets underlying smooth myocytes
to maintain a relaxation state.
Artery wall adaptation to hemodynamical stresses not only results from local
mechanotransduction by vascular endothelial and smooth muscle cells mainly via
ion channels, receptors, and adhesion molecules (Tables 9.32 and 9.33 ), but also

regulation by hormones and growth factors (Fig. 9.12 ).