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To the Editor: Dr Bodary and colleagues1 found that leptin contributed to arterial thrombosis following photochemical vascular injury in mice. Recently, Konstantinides et al2 reported similar results with the ferric chloride model of carotid artery injury. A common factor of these findings may be the ability of leptin to enhance platelet aggregation through the stimulation of the long form of its receptor on the platelet membrane.2 - 4
The findings of Bodary et al provide further support to the hypothesis that a direct adipocyte-platelet interaction contributes to the excess risk of cardiovascular events in obesity. However, Bodary et al state that "these findings raise the possibility that therapeutic strategies aimed at reducing plasma leptin levels may reduce cardiovascular events." Although they acknowledge the potential adverse effects of a drug-induced leptin reduction, they invoke "a strategy specifically targeting the leptin receptor on the platelet."
We think that studies in this field are still in their early stages, and further investigation is required for at least 2 reasons. First, most obese individuals have elevated plasma leptin levels, and human obesity is known to be associated with resistance to leptin effect in the hypothalamus.5 However, whether platelets may be resistant to leptin in obese patients is still unknown. Second, second messengers other than Janus kinase-regulated signal transducer and activator of transcription (STAT-) proteins tyrosine phosphorylation (eg, mitogen-activated protein kinases, phospholipase C, and intracellular calcium) may be involved in leptin signal transduction at the postreceptor level in other cell types in a porcine model,6 but whether this is also true for human platelets is unknown.
It is premature to search for biological targets before the mechanisms of leptin in the regulation of hemostasis and the pathophysiology of obesity-related atherothrombotic complications are better understood. Administration of high doses of leptin also may increase the risk of thrombotic events.2
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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