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) ( ) and adiponectin knockout (Adipoq？/？) mice ( ). 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 ( ) and Ccl5 ( ), and vascular adhesion molecules, such as Icam1 ( ), and Vcam1 ( ), 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 ( ). Overall, capillary density was positively correlated with Sca-1+ PC numbers in BM ( ) and peripheral blood (PB) ( ) and with the expression of the homing factors Cxcl12 ( ), Icam1 ( ) and Vcam1 ( ). 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. 1. Introduction Cardiovascular disease (CVD) is a major cause of illness and death in industrialized countries [1]. Moreover, the increasing incidence of CVD is largely due to the global epidemic of obesity [2] and obesity-related comorbidities, such as diabetes mellitus [3]. As a consequence, the pathophysiological role of adipose tissues in the development of CVD has recently gained much attention. Adipose tissue is nowadays considered to be an important endocrine organ [4], secreting a number of hormones, adipocytokines, which are of prime importance in the metabolic complications of obesity [5]. One specific adipocytokine, adiponectin, has been reported to offer cardiovascular protection in addition to its beneficial effects on insulin sensitivity. Some of the mechanisms, by which adiponectin exerts its antiatherogenic and anti-inflammatory properties, were reviewed by Goldstein et al. [6] and related to a reduction in the generation of reactive oxygen species (ROS), attenuation of the levels of proinflammatory cytokines, such as TNFα, and activation of endothelial nitric oxide synthase (eNOS). Clinically, adiponectin is inversely correlated with fasting plasma glucose and insulin levels and reduced in patients with type 2 diabetes mellitus and coronary artery disease [7].
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