Publikation

Serotonin reverts age-related capillarization and failure of regeneration in the liver through a VEGF-dependent pathway

Wissenschaftlicher Artikel/Review - 31.01.2011

Bereiche
PubMed
DOI

Zitation
Furrer K, Moritz W, Graf R, Humar B, Käch A, Bittermann A, Jochum W, Tian Y, Rickenbacher A, Clavien P. Serotonin reverts age-related capillarization and failure of regeneration in the liver through a VEGF-dependent pathway. Proc Natl Acad Sci USA 2011; 108:2945-50.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Proc Natl Acad Sci USA 2011; 108
Veröffentlichungsdatum
31.01.2011
eISSN (Online)
1091-6490
Seiten
2945-50
Kurzbeschreibung/Zielsetzung

The function of the liver is well-preserved during the aging process, although some evidence suggests that liver regeneration might be impaired with advanced age. We observed a decreased ability of the liver to restore normal volume after partial hepatectomy in elderly mice, and we identified a pathway that rescued regeneration and was triggered by serotonin. 2,5-dimethoxy-4-iodoamphetamine (DOI), a serotonin receptor agonist, reversed the age-related pseudocapillarization of old liver and improved hepatosinusoidal blood flow. After hepatectomy, the open fenestrae were associated with a restored attachment of platelets to endothelium and the initiation of a normal regenerative response, including the up-regulation of essential growth mediators and serotonin receptors. In turn, hepatocyte proliferation recovered along with regain of liver volume and animal survival. DOI operates through the release of VEGF, and its effects could be blocked with anti-VEGF antibodies both in vitro and in vivo. These results suggest that pseudocapillarization in the aged acts as a barrier to liver regeneration. DOI breaks this restraint through an endothelium-dependent mechanism driven by VEGF. This pathway highlights a target for reversing the age-associated decline in the capacity of the liver to regenerate.