Role of Adiponectin in Cardiovascular Protection

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp therosclerosis is a pathological injury-to-response process that is initiated by early inflammatory responses of vascular endothelial cells. Endothelial inflammation is characterized by decreased nitric oxide (NO) formation, platelet adherence to endothelium, monocyte adhesion and migration into the neointima lesion, followed by transformation of macrophages into foam cells. Subsequently, oxidized low-density lipoproteins accumulate in the atherosclerotic plaques forming lipid or necrotic core. Vascular smooth muscle cell (VSMC) proliferation and migration, and extracellular matrix (ECM) formation/degradation also play important roles in the development of plaque formation and destabilization. During this process, various cytokines/chemokines, reactive oxygen free radicals and various proteases released from macrophages, platelets and VSMCs contribute to the progression of complicated atherosclerosis. Article p 552Recently, adipocytes are believed as not only simple energy-storing cells but also function as active secretory cells. Adipocytes release several cytokines including tumor necrosis factor (TNF)-α, leptin, interleukins, angiotensinogen and adiponectin. The majority of these adipokines causes inflammation in the arterial wall, resulting in endothelial dysfunction, macrophage accumulation and VSMC proliferation/ migration. These adipokines are believed to play an important role in the progression of atherosclerosis.In contrast to the inflammatory adipokines, adiponectin has been reported to increase insulin sensitivity and to suppress atherosclerosis. Adiponectin is a 30-kDa protein that contains an N-terminal collagenous domain and C-terminal globular domain, and the most abundant adipokine secreted from adipocytes. The plasma concentrations of adiponectin decreased in patients with obesity, type 2 diabetes mellitus, hypertension, and metabolic syndrome. 1 Adiponectin suppresses endothelial adhesion molecule expression, which interferes with monocyte adhesion/migration and transition to foam cells. Adiponectin also suppresses the proliferation of VSMCs. In fact, neointimal thickning due to arterial injury is increased in adiponetin-knockout mice compared to wild-type animals. These data collectively suggest that adiponectin works to prevent atherosclerosis. Interestingly, there was a significant difference of plasma adiponectin concentrations between the longevity and non-longevity districts in Japan. 2 Low plasma adiponectin concentrations were associated with increased prevalence of myocardial infarction and cardiovascular mortality. 3, 4 In this issue of the Journal, Li and co-workers reported the effects of adiponectin on stability of pre-existing plaques. They have identified a novel mechanism by which adiponectin stimulates the expression of prolyl 4-hydroxylase (P4H) that induces extracellular matrix synthesis. 5 They identified that the administration of adiponectin stabilized plaques as documented b...

Obesity and ischemic heart disease. Is there a link between wellness’ diseases?

“…Il gene dell'adiponectina nell'essere umano è posizionato sul cromosoma 3q27 [15]. L'Adiponectina ad oggi è l'unica adipochina nota per i suoi effetti protettivi sull'apparato cardiovascolare [16] È noto infatti da tempo che l'espressione di questa adipochina è diminuita nei soggetti obesi e in quelli con sindrome metabolica o diabete mellito. Studi recenti dimostrano nello specifico come bassi livelli di Adiponectina possano essere predittivi della presenza e del grado di aterosclerosi [17] così come essere associati alla progressione di malattia in pazienti con angina pectoris [18].…”