PMID- 19332545 OWN - NLM STAT- MEDLINE DCOM- 20090806 LR - 20211020 IS - 0021-9258 (Print) IS - 1083-351X (Electronic) IS - 0021-9258 (Linking) VI - 284 IP - 26 DP - 2009 Jun 26 TI - Abscisic acid released by human monocytes activates monocytes and vascular smooth muscle cell responses involved in atherogenesis. PG - 17808-18 LID - 10.1074/jbc.M809546200 [doi] AB - 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. FAU - Magnone, Mirko AU - Magnone M AD - 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. FAU - Bruzzone, Santina AU - Bruzzone S FAU - Guida, Lucrezia AU - Guida L FAU - Damonte, Gianluca AU - Damonte G FAU - Millo, Enrico AU - Millo E FAU - Scarfi, Sonia AU - Scarfi S FAU - Usai, Cesare AU - Usai C FAU - Sturla, Laura AU - Sturla L FAU - Palombo, Domenico AU - Palombo D FAU - De Flora, Antonio AU - De Flora A FAU - Zocchi, Elena AU - Zocchi E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090330 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Chemokine CCL2) RN - 0 (Hemostatics) RN - 0 (NF-kappa B) RN - 0 (Plant Growth Regulators) RN - 0 (RNA, Messenger) RN - 72S9A8J5GW (Abscisic Acid) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - EC 3.4.21.5 (Thrombin) RN - K7Q1JQR04M (Dinoprostone) RN - SY7Q814VUP (Calcium) SB - IM MH - Abscisic Acid/*pharmacology MH - Aorta/cytology/metabolism MH - Atherosclerosis/*metabolism/pathology MH - Blotting, Western MH - Calcium/metabolism MH - Cell Movement MH - Cell Proliferation MH - Cells, Cultured MH - Chemokine CCL2/metabolism MH - Cyclooxygenase 2/metabolism MH - Dinoprostone/metabolism MH - Hemostatics/pharmacology MH - Humans MH - Monocytes/*drug effects/metabolism MH - Muscle, Smooth, Vascular/*drug effects/metabolism MH - NF-kappa B/metabolism MH - Plant Growth Regulators/*pharmacology MH - Platelet Activation/drug effects MH - Protein Transport MH - RNA, Messenger/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Second Messenger Systems MH - Thrombin/pharmacology PMC - PMC2719419 EDAT- 2009/04/01 09:00 MHDA- 2009/08/07 09:00 PMCR- 2010/06/26 CRDT- 2009/04/01 09:00 PHST- 2009/04/01 09:00 [entrez] PHST- 2009/04/01 09:00 [pubmed] PHST- 2009/08/07 09:00 [medline] PHST- 2010/06/26 00:00 [pmc-release] AID - S0021-9258(19)82063-X [pii] AID - M809546200 [pii] AID - 10.1074/jbc.M809546200 [doi] PST - ppublish SO - J Biol Chem. 2009 Jun 26;284(26):17808-18. doi: 10.1074/jbc.M809546200. Epub 2009 Mar 30.