Increased tissue transglutaminase activity contributes to central vascular stiffness in eNOS knockout mice

Sung Mee Jung, Simran Jandu, Jochen Steppan, Alexey Belkin, Steven S. An, Alina Pak, Eric Y. Choi, Daniel Nyhan, Mark Butlin, Kayla Viegas, Alberto Avolio, Dan E. Berkowitz, Lakshmi Santhanam

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Nitric oxide (NO) can modulate arterial stiffness by regulating both functional and structural changes in the arterial wall. Tissue transglutaminase (TG2) has been shown to contribute to increased central aortic stiffness by catalyzing the cross-linking of matrix proteins. NO S-nitrosylates and constrains TG2 to the cytosolic compartment and thereby holds its cross-linking function latent. In the present study, the role of endothelial NO synthase (eNOS)-derived NO in regulating TG2 function was studied using eNOS knockout mice. Matrix-associated TG2 and TG2 crosslinking function were higher, whereas TG2 S-nitrosylation was lower in the eNOS-/- compared with wild-type (WT) mice. Pulse-wave velocity (PWV) and blood pressure measured noninvasively were elevated in the eNOS-/- compared with WT mice. Intact aortas and decellularized aortic tissue scaffolds of eNOS-/- mice were significantly stiffer, as determined by tensile testing. The carotid arteries of the eNOS-/- mice were also stiffer, as determined by pressuredimension analysis. Invasive methods to determine the PWV-mean arterial pressure relationship showed that PWV in eNOS-/- and WT diverge at higher mean arterial pressure. Thus eNOS-derived NO regulates TG2 localization and function and contributes to vascular stiffness.

Original languageEnglish (US)
Pages (from-to)H803-H810
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6
StatePublished - Sep 15 2013


  • Endothelial nitric oxide synthase
  • Nitric oxide
  • Pulse-wave velocity
  • S-nitrosylation
  • Tensile testing
  • Tissue transglutaminase
  • Vascular stiffness

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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