The Effect of BAPN on Heart Structure and Function in the Angiotensin II Hypertensive Mouse

Abstract

Lysyl oxidase (LOX) is the enzyme that mediates cross-linking between collagen and elastin molecules during cardiac remodeling, LOX expression and activity is upregulated in response to the mechanical stresses that occur during hypertension. The aim of this study was to investigate the role of lysl oxidase (LOX) changes in cardiac structure and mechanical function during angiotensin II (AngII) induced hypertension. C57 male mice were given the LOX suicide substrate: β-aminoproprionitrile (BAPN) in their drinking water (300mg/kg/d). On day 14 of BAPN treatment an osmotic pump of AngII (490ng/kg/hr) was implanted. Weekly echo measurements were gathered. 28 days after pump implantation cardiac tissue was harvested for various assays including, LOX enzymatic activity, hydroxyproline quantification, and histological analysis. AngII treated groups showed an increase LOX protein expression, LOX activity, collagen cross-linking, and total collagen content while ECHO results showed an up-regulation aortic velocity time integral (AoVTI) and LV mass and down regulation of E/E-A VTI. When BAPN was co administered with AngII there was an attenuation seen in all these areas. While AngII+BAPN treated mice showed a return of these parameters to normal control levels. These results provide evidence that Angiotensin II-Induced hypertension causes the overexpression of LOX. LOX's overstimulation has a major influence in the cardiac structure and function. Conversely both the structural and mechanical changes can be extenuated with administration of the LOX suicide substrate BAPN.