oa Endothelial Adiponectin: Putative Role In Graft Patency In Patients Undergoing Coronary Artery Bypass Surgery?

Background: Blood vessels are comprised of three distinct layers, the intima, media and outermost layer, the adventitia that, in medium to large vessels, is surrounded by a cushion of perivascular adipose tissue (PVAT). PVAT is comprised of discrete adipocytes containing a network of capillaries and nerve fibres as well as a variety of other cell types. A number of adipokines have been identified in the PVAT of human blood vessels, including leptin and adiponectin. Since PVAT is in close proximity with the adventitia there is the potential for this layer to influence vessel tone and therefore blood flow. Of particular interest is the beneficial role PVAT may play in blood vessels used as bypass grafts in patients requiring coronary artery bypass grafting (CABG). This study investigated the expression of leptin and adiponectin in the main vessels used as bypass conduits, which include the internal thoracic artery (ITA) and saphenous vein (SV). Methods and Results: SV and ITA samples were obtained at heart surgery - all with PVAT intact. 'Local' subcutaneous fat (SV=calf/thigh; ITA = sternum) was also collected and used for: 1) ELISA, 2) histology and IHC vessels and, 3) mRNA expression. Human arterial and venous endothelial cell lines were established to ascertain endothelial leptin and adiponectin synthesis and regulation. Dense immunostaining for leptin was observed in the PVAT of both the vein and artery with no evidence of staining associated with endothelial cells lining the vessel lumen, the vasa vasorum or capillaries (as identified using CD31). Like leptin there was dense immunostaining for adiponectin in both the vein and the artery. However, discrete staining was also associated with endothelial cells lining the lumen of both the artery and the vein as well as to those of the vasa vasorum and capillaries embedded in PVAT. No leptin mRNA expression was detectable in either arterial or venous endothelial cell lines, however, adiponectin was present in both and appeared inducible by insulin. Conclusions: We show, for the first time, that the endothelium expresses adiponectin and that endothelial cell adiponectin appears to increase upon insulin stimulation. Whether these adiponectin concentrations are of functional importance in the endothelium and contribute to the vasodilatory capacity of grafted vessels are yet to be ascertained.