SP1 and Hyperglycemia: However, it has been observed that hyperglycemia causes a fourfold increase in O-GlcN acylation of the transcription factor specificity protein 1 (Sp1), which mediates hyperglycemia-induced activation of the plasminogen activator inhibitor-1 (PAI-1) promoter in vascular smooth muscle cells and of TGF-β1 and PAI-1 in arterial endothelial cells (Figure 1) [28].