Vascular ATGL-dependent lipolysis and the activation of cPLA2-PGI2 pathway protect against postprandial endothelial dysfunction.

Adipose triglyceride lipase (ATGL) is involved in lipolysis and displays a detrimental pathophysiological role in cardio-metabolic diseases. However, the organo-protective effects of ATGL-induced lipolysis were also suggested. The aim of this work was to characterize the function of lipid droplets (LDs) and ATGL-induced lipolysis in the regulation of endothelial function. ATGL-dependent LDs hydrolysis and cytosolic phospholipase A2 (cPLA2)-derived eicosanoids production were studied in the aorta, endothelial and smooth muscle cells exposed to exogenous oleic acid (OA) or arachidonic acid (AA). Functional effects of ATGL-dependent lipolysis and subsequent activation of cPLA2/PGI2 pathway were also studied in vivo in relation to postprandial endothelial dysfunction.The formation of LDs was invariably associated with elevated production of endogenous AA-derived prostacyclin (PGI2). In the presence of the inhibitor of ATGL or the inhibitor of cytosolic phospholipase A2, the production of eicosanoids was reduced, with a concomitant increase in the number of LDs. OA administration impaired endothelial barrier integrity in vitro that was further impaired if OA was given together with ATGL inhibitor. Importantly, in vivo, olive oil induced postprandial endothelial dysfunction that was significantly deteriorated by ATGL inhibition, cPLA2 inhibition or by prostacyclin (IP) receptor blockade.In summary, vascular LDs formation induced by exogenous AA or OA was associated with ATGL- and cPLA2-dependent PGI2 production from endogenous AA. The inhibition of ATGL resulted in an impairment of endothelial barrier function in vitro. The inhibition of ATGL-cPLA2-PGI2 dependent pathway resulted in the deterioration of endothelial function upon exposure to olive oil in vivo. In conclusion, vascular ATGL-cPLA2-PGI2 dependent pathway activated by lipid overload and linked to LDs formation in endothelium and smooth muscle cells has a vasoprotective role by counterbalancing detrimental effects of lipid overload on endothelial function.

Influence of 6-metoxy-cumaranon-2-acetic acid and its derivatives on the process of humoral and cellular immunogenesis.

The influence of 6-metoxy-cumaranon-2-acetic acid and its four derivatives on the humoral and cellular immunogenesis was determined. The study of immunosuppressive properties included: the control of the level of peripheral blood lymphocytes, the estimation of transplantation immunity, GvH reaction, PFC production for SRBC and LPS and the determination of the number of cells possessing receptors for antigen, Fc fragment and complement. Furthermore, blast transformation of lymphocytes stimulated with PHA was estimated as well as the cytotoxic effect of sensitized lymphocytes. The results indicate immunosuppressive activity of acetamides HKCMF and HKCHF. They lowered the level of circulating lymphocytes, the number of cells possessing receptors for complement and they hindered PFC production for SRBC and LPS. Moreover, acetamide HKCHF weakened the cytotoxic activity of lymphocytes sensitized to alloantigens.

The influence of aminoguanidine derivatives on the process of humoral and cellular immunogenesis.

The influence of six aminoguanidine derivatives on the process of humoral and cellular immunogenesis was examined. The obtained results can be presented in the following items: 1. Strong action inhibiting the primary humoral response was found in mice of Balb/c strain where the decrease of PFC number in spleen was from 34.8% to 96.7%; only the second preparation (D-mannose-ylidene-aminoguanidine) (HCl) caused a significant increase of PFC number and thus, on the contrary, exerted the action stimulating the humoral immunological response. 2. Among the examined preparations only three (third, fourth and fifth) showed the action inhibiting MIF production (the decrease within 30-50%) and only these three preparations caused a clear prolongation of allograft survival in the pattern: Balb/c-recipient, C3H-skin graft donor. 3. The clear decrease of the number of lymphocytes in peripheral blood was found (within 40-60%) as a result of administering aminoguanidine derivatives. 4. Synergism was not found to occur when administering jointly ALS and aminoguanidine derivatives, with the aim of prolonging allograft survival or inhibiting MIF production.