Isolevuglandin scavenger attenuates pressure overload-induced cardiac oxidative stress, cardiac hypertrophy, heart failure and lung remodeling

Abstract

Increased levels of reactive isolevuglandins (IsoLGs) are associated with vascular inflammation and hypertension, two important factors affect heart failure (HF) development. The role of IsoLGs in HF development is unknown. Here we studied the role of IsoLG scavenger 2-hydroxybenzylamine (2-HOBA) in transverse aortic constriction (TAC) induced heart failure. We observed that TAC caused a significant increase of IsoLG protein adducts in cardiac and lung tissues in mice. Both IsoLG scavenger 2-hydroxybenzylamine (2-HOBA) and its less reactive isomer 4-hydroxybenzylamine (4-HOBA) significantly attenuated the left ventricular (LV) and lung IsoLGs in mice after TAC. 2-HOBA and 4-HOBA attenuated TAC-induced LV hypertrophy, heart failure, and the increase of lung weight in mice, and also improved TAC-induced LV dysfunction. Moreover, both 2-HOBA and 4-HOBA effectively attenuated LV cardiomyocyte hypertrophy, lung inflammation, lung fibrosis. These findings suggest that methods to reduce IsoLGs may be useful for HF therapy.

Keywords: Cardiac hypertrophy; Fibrosis; Heart failure; Inflammation; Lung.