Proangiogenic activity of beta-carotene is coupled with the activation of endothelial cell chemotaxis.
Endothelial cells play an important role in angiogenesis (formation of new vessels from preexisting ones), which is essential for organogenesis, tissue remodeling but also inflammatory response, carcinogenesis in all periods of our life. Beta-carotene (BC) in non-toxic concentrations (up to 3 microM) had no detectable effect on HUVECs (human umbilical vein endothelial cells) proliferation or apoptosis, despite significant changes of the expression patterns of pro- and anti-apoptotic genes. However beta-carotene did not change the tubulogenic activity of HUVEC in the in vitro angiogenesis model, it potently accelerated the bFGF-induced development of microcapillaries, as well as the migration of endothelial cells, in matrigel plug injected subcutaneously to mice. Potent activation of endothelial cell migration in the in vitro model of chemotaxis was also observed. According to the microarray data, genes involved in cell/cell and cell/matrix adhesion, matrix reorganization, activation of chemotaxis, the G-protein regulated intracellular signaling as well as genes involved in the rapid remodeling of protein cytoskeleton were the most affected by BC in HUVEC. We conclude that beta-carotene in the physiological concentration range stimulates early steps of angiogenesis by the activation of cellular migration as well as matrix reorganization and decrease of cell adhesion.
Dembinska-Kiec
A
A
Department of Clinical Biochemistry, The Jagiellonian University Medical College, Kopernika 15a, 31-501 Kraków, Poland. mbkiec@cyf-kr.edu.pl
Polus
A
A
Kiec-Wilk
B
B
Grzybowska
J
J
Mikolajczyk
M
M
Hartwich
J
J
Razny
U
U
Szumilas
K
K
Banas
A
A
Bodzioch
M
M
Stachura
J
J
Dyduch
G
G
Laidler
P
P
Zagajewski
J
J
Langman
T
T
Schmitz
G
G
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D016718:Arachidonic Acid / Q000494:pharmacology; D049109:Cell Proliferation; D002633:Chemotaxis / Q000187:drug effects* / Q000235:genetics; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D046228:Microarray Analysis; D008870:Microtubules / Q000235:genetics; D016133:Polymerase Chain Reaction; D019207:beta Carotene / Q000494:pharmacology*
D043925:Angiogenesis Inducing Agents; D019207:beta Carotene; D016718:Arachidonic Acid