Epidemiological evidence strongly links excess body weight with an increased risk to develop atherothrombotic complications.
Obesity is frequently associated with systemic and local inflammation as well as elevated circulating leptin levels, and clinical studies
found hyperleptinemia to correlate not only with measures of adiposity, but also with circulating biomarkers of an increased metabolic
and cardiovascular risk or surrogate markers of subclinical atherosclerosis. Moreover, experimental studies in mice with systemic disruption
of the leptin-leptin receptor system as well as after administration or neutralization of the adipokine demonstrated that leptin promotes
both arterial and venous thrombosis. In addition to directly binding to and activating platelets and thus potentiating their aggregation
in response to agonist stimulation, leptin enhances the expression of prothrombotic and anti-fibrinolytic proteins in vascular and inflammatory
cells. On the other hand, its ability to mobilize and recruit vascular progenitor cells from the bone marrow to sites of vascular
injury was found to be impaired in hyperleptinemic, obese humans and rodents. Thus, leptin promotes thrombus formation and resolution
by several different mechanisms involving primary hemostasis, the coagulation cascade as well as the integrity of the vessel wall. Dissection
of the molecular mechanisms underlying each of its actions may pave the road for novel therapeutic options in targeting the increased
risk of thrombosis associated with obesity, keeping in mind unresolved issues of a cell-specific leptin resistance as well as individual
differences in the responsiveness to leptin.
Keywords: Adipokines, cardiovascular risk, leptin, obesity, platelets, thrombosis.
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