Leukocyte iNOS is required for inflammation and pathological remodeling in ischemic heart failure.

ABSTRACT: In the failing heart, iNOS is expressed by both macrophages and cardiomyocytes. We hypothesized that inflammatory cell-localized iNOS exacerbates left ventricular (LV) remodeling. Wild-type (WT) C57BL/6 mice underwent total body irradiation and reconstitution with bone marrow from iNOS^-/- mice (iNOS^-/-c) or WT mice (WTc). Chimeric mice underwent coronary ligation to induce large infarction and ischemic heart failure (HF), or sham surgery. After 28 days, as compared with WTc sham mice, WTc HF mice exhibited significant (p < 0.05) mortality, LV dysfunction, hypertrophy, fibrosis, oxidative/nitrative stress, inflammatory activation, and iNOS upregulation. These mice also exhibited a ~twofold increase in circulating Ly6C^hi pro-inflammatory monocytes, and ~seven

SUBMITTER: Kingery JR 

PROVIDER: S-EPMC5555149 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature