Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury.

ABSTRACT:

Background

Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart.

Methods and results

We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of

SUBMITTER: Sawicki KT 

PROVIDER: S-EPMC4599478 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature