title: Adiponectin deficiency blunts hypoxia-induced mobilization and homing of circulating angiogenic cells.
abstract: Aim. We investigated the effects of adiponectin deficiency on circulating angiogenic cell (CAC) mobilization, homing, and neovascularization in the setting of acute myocardial infarction (AMI). Methods & Results. AMI was induced in wild-type (WT) (n = 10) and adiponectin knockout (Adipoq (-/-)) mice (n = 7). One week after AMI, bone marrow (BM) concentration and mobilization of Sca-1(+) and Lin(-)Sca-1(+) progenitor cells (PCs) were markedly attenuated under Adipoq (-/-) conditions, as assessed by flow cytometry. The mRNA expression of HIF-1-dependent chemotactic factors, such as Cxcl12 (P = 0.005) and Ccl5 (P = 0.025), and vascular adhesion molecules, such as Icam1 (P = 0.010), and Vcam1 (P = 0.014), was significantly lower in the infarction border zone of Adipoq (-/-) mice. Histologically, Adipoq (-/-) mice evidenced a decrease in neovascularization capacity in the infarction border zone (P < 0.001). Overall, capillary density was positively correlated with Sca-1(+) PC numbers in BM (P = 0.01) and peripheral blood (PB) (P = 0.005) and with the expression of the homing factors Cxcl12 (P = 0.013), Icam1 (P = 0.034) and Vcam1 (P = 0.014). Conclusions. Adiponectin deficiency reduced the BM reserve and mobilization capacity of CACs, attenuated the expression of hypoxia-induced chemokines and vascular adhesion molecules, and impaired the neovascularization capacity one week after AMI.
authors.affiliation: Laboratory of Cell Biology and Histology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium ; Laboratory of Cellular and Molecular Cardiology, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium.
authors.forename: Bert R
authors.initials: BR
authors.lastname: Everaert
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Nijenhuis
authors.forename: Florence C M
authors.initials: FC
authors.lastname: Reith
authors.forename: Vicky Y
authors.initials: VY
authors.lastname: Hoymans
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Timmermans
authors.forename: Christiaan J
authors.initials: CJ
authors.lastname: Vrints