Regulation of apoptotic resistance of endothelial cells is important for endothelial cell function. We could show that PTHrP modifies the expression of the antiapoptotic gene bcl-2. By gene-array-analyzes we identified TIMP-1 as another potentially co-regulated PTHrP protein in coronary endothelial cells. The aim of our investigation was to validate these data for basal and pathophysiological changes in the PTHrP expression. Coronary endothelial cells were isolated from male wistar rats. Analyzes of expression were performed by real-time RT-PCR and immunoblotting. Endogenous PTHrP Protein generation was down-regulated by transformation with antisense-oligonucleotides by 51±12%. Under these conditions TIMP-1 expression was reduced by 41±6% (n=5, p=0.018) and TIMP-2 by 49±6% (n=5, p=0.013). TGF-b lowered likewise the expression of PTHrP, and that of TIMP-1 and TIMP-2. a-adrenergic stimulation increased PTHrP expression and enhanced TIMP-1 expression in a PTHrP-dependent way. This enhancement could not further be increased under these conditions in those cells, which were transformed with antisense-oligonucleotides against PTHrP. In conclusion, endothelial expression of TIMP-1 is co-regulated by PTHrP. An elevated endothelial expression of PTHrP enhances apoptotic resistance by increasing bcl-2 and TIMP-1 expression.