Effect of lysyl oxidase inhibition on angiotensin ii-induced arterial hypertension, remodeling, and stiffness

Lance S. Eberson, Pablo A. Sanchez, Beenish A. Majeed, Supannikar Tawinwung, Timothy W Secomb, Douglas F Larson

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

It is well accepted that angiotensin II (Ang II) induces altered vascular stiffness through responses including both structural and material remodeling. Concurrent with remodeling is the induction of the enzyme lysyl oxidase (LOX) through which ECM proteins are crosslinked. The study objective was to determine the effect of LOX mediated cross-linking on vascular mechanical properties. Three-month old mice were chronically treated with Ang II with or without the LOX blocker, β -aminopropionitrile (BAPN), for 14 days. Pulse wave velocity (PWV) from Doppler measurements of the aortic flow wave was used to quantify in vivo vascular stiffness in terms of an effective Young's modulus. The increase in effective Young's modulus with Ang II administration was abolished with the addition of BAPN, suggesting that the material properties are a major controlling element in vascular stiffness. BAPN inhibited the Ang II induced collagen cross-link formation by 2-fold and PWV by 44% (P<0.05). Consistent with this observation, morphometric analysis showed that BAPN did not affect the Ang II mediated increase in medial thickness but significantly reduced the adventitial thickness. Since the hypertensive state contributes to the measured in vivo PWV stiffness, we removed the Ang II infusion pumps on Day 14 and achieved normal arterial blood pressures. With pump removal we observed a decrease of the PWV in the Ang II group to 25% above that of the control values (P=0.002), with a complete return to control values in the Ang II plus BAPN group. In conclusion, we have shown that the increase in vascular stiffness with 14 day Ang II administration results from a combination of hypertension- induced wall strain, adventitial wall thickening and Ang II mediated LOX ECM crosslinking, which is a major material source of vascular stiffening, and that the increased PWV was significantly inhibited with co-administration of BAPN.

Original languageEnglish (US)
Article numbere0124013
JournalPLoS One
Volume10
Issue number4
DOIs
StatePublished - Apr 13 2015

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Protein-Lysine 6-Oxidase
angiotensins
angiotensin II
Angiotensins
Angiotensin II
Aminopropionitrile
hypertension
Stiffness
Hypertension
Pulse Wave Analysis
blood vessels
Vascular Stiffness
Military electronic countermeasures
Adventitia
Elastic Modulus
crosslinking
modulus of elasticity
pumps
Blood Vessels
Elastic moduli

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Effect of lysyl oxidase inhibition on angiotensin ii-induced arterial hypertension, remodeling, and stiffness. / Eberson, Lance S.; Sanchez, Pablo A.; Majeed, Beenish A.; Tawinwung, Supannikar; Secomb, Timothy W; Larson, Douglas F.

In: PLoS One, Vol. 10, No. 4, e0124013, 13.04.2015.

Research output: Contribution to journalArticle

Eberson, Lance S. ; Sanchez, Pablo A. ; Majeed, Beenish A. ; Tawinwung, Supannikar ; Secomb, Timothy W ; Larson, Douglas F. / Effect of lysyl oxidase inhibition on angiotensin ii-induced arterial hypertension, remodeling, and stiffness. In: PLoS One. 2015 ; Vol. 10, No. 4.
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