Pressure- And Flow-Dependent Vascular Remodeling In Mice Deficient For Tissue-Type Transglutaminase

Tissue-type transglutaminase (tTG) acts as a biological glue by cross-linking extracellular matrix proteins. We tested whether tTG plays a role in the remodeling of small arteries in hypertension and reduced blood flow. Mice were given L-NAME to induce hypertension. Blood pressure increased similarly in wild type (WT) and tTG null mice (119 ± 3 to 144 ± 4 mmHg vs. 115 ± 3 to 137 ± 5 mmHg). After one week, mesenteric arteries were isolated and pressure-diameter relationships were determined in vitro under fully dilated conditions. WT mice showed inward remodeling (−10%), whereas tTG null mice did not (+3%), expressed as difference in lumen diameter at 80 mmHg. In the second series of experiments, blood flow was modified in mesenteric arteries by a surgical intervention. Two days after a reduction in blood flow arteries of WT mice showed inward remodeling (−17 ± 3%) while vessels from tTG null mice did not (0 ± 2%). However, after 7 days inward remodeling in WT and tTG null mice was similar: −18 ± 1% vs. −21 ± 2%. While tTG null mice lacked tTG expression, arteries did show the cross-link specific for transglutaminases. RT-PCR revealed the expression of type 1 transglutaminase and the plasma transglutaminase, Factor XIII in both WT and tTG null mice. These data show that tTG plays a crucial role in the inward remodeling of small arteries in both hypertension and reduced blood flow. Other transglutaminases are expressed but do not fully compensate when arteries are challenged with a remodeling stimulus. Supported by the Netherlands Heart Foundation (NHS 2001.D038).