Adiponectin, ghrelin, and leptin differentially influence human platelet and human vascular endothelial cell functions: implication in obesity-associated cardiovascular diseases.
A very strong epidemiological link exists between obesity, the metabolic syndrome, diabetes and diabetes-associated cardiovascular pathologies. For this reason the peripheral effects of the centrally-acting satiety adipokines, adiponectin and leptin, and of non-adipose-derived hormones with similar effects, like ghrelin, have received considerable attention. In this report, we have extended our previous studies of the pro-thrombotic effects of leptin and determined the effects of adiponectin or ghrelin on human platelet activation. Thus, while leptin stimulated human platelet aggregation and adhesion, addition of adiponectin or of ghrelin did not affect either aggregation or adhesion of these cells; even at supra-physiological concentrations. In addition, we compared the impact of these three important hormones on microvascular endothelial cell permeability, an important parameter of endothelial function that when impaired contributes to several vascular pathologies. While physiologically relevant concentrations of either leptin or adiponectin increased the integrity of the diffusion barrier formed by a monolayer of human microvascular endothelial cells, only supra-physiological concentrations of ghrelin had this effect. None of these agents reduced microvascular endothelial barrier function. Taken together, our data are consistent with the ideas that leptin activates human platelets and limits transendothelial cell diffusion but that adiponectin only influences endothelial cell permeability. In contrast, ghrelin had neither of these effects. We propose that these data identify important differences in the effects of leptin, adiponectin or ghrelin on microvascular endothelial cells and platelets and may provide a basis on which to pharmacologically manipulate the selective effects of these peptides on these cell types in human cardiovascular or thrombotic diseases associated with obesity.
Elbatarny
Hisham S
HS
Department of Pharmacology and Toxicology, Botterell Hall, 229, Queen's University, Kingston, ON, Canada.
Netherton
Stuart J
SJ
Ovens
Jeffrey D
JD
Ferguson
Alastair V
AV
Maurice
Donald H
DH
D052242:Adiponectin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D054439:Ghrelin; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D009765:Obesity / Q000150:complications*; D036361:Peptide Hormones / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects
D052242:Adiponectin; D054439:Ghrelin; D020738:Leptin; D036361:Peptide Hormones