Abscisic acid released by human monocytes activates monocytes and vascular smooth muscle cell responses involved in atherogenesis.
Abscisic acid (ABA) is a phytohormone recently identified as a new endogenous pro-inflammatory hormone in human granulocytes. Here we report the functional activation of human monocytes and vascular smooth muscle cells by ABA. Incubation of monocytes with ABA evokes an intracellular Ca2+ rise through the second messenger cyclic ADP-ribose, leading to NF-kappaB activation and consequent increase of cyclooxygenase-2 expression and prostaglandin E2 production and enhanced release of MCP-1 (monocyte chemoattractant protein-1) and of metalloprotease-9, all events reportedly involved in atherogenesis. Moreover, monocytes release ABA when exposed to thrombin-activated platelets, a condition occurring at the injured vascular endothelium; monocyte-derived ABA behaves as an autocrine and paracrine pro-inflammatory hormone-stimulating monocyte migration and MCP-1 release, as well as vascular smooth muscle cells migration and proliferation. These results, and the presence of ABA in human arterial plaques at a 10-fold higher concentration compared with normal arterial tissue, identify ABA as a new signal molecule involved in the development of atherosclerosis and suggest a possible new target for anti-atherosclerotic therapy.
Magnone
Mirko
M
Department of Experimental Medicine, Section of Biochemistry and Center of Excellence for Biomedical Research, University of Genova, and Vascular and Endovascular Surgery Unit, San Martino Hospital, Viale Benedetto XV 1, 16132 Genova, Italy.
Bruzzone
Santina
S
Guida
Lucrezia
L
Damonte
Gianluca
G
Millo
Enrico
E
Scarfì
Sonia
S
Usai
Cesare
C
Sturla
Laura
L
Palombo
Domenico
D
De Flora
Antonio
A
Zocchi
Elena
E