Premium
PRESSURE‐ AND FLOW‐DEPENDENT VASCULAR REMODELING IN MICE DEFICIENT FOR TISSUE‐TYPE TRANSGLUTAMINASE
Author(s) -
Bakker Erik,
Pistea Adrian,
Spaan Jos AE,
VanBavel Ed
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a710-b
Subject(s) - tissue transglutaminase , mesenteric arteries , extracellular matrix , medicine , endocrinology , blood flow , chemistry , pathology , artery , enzyme , biochemistry
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).