Leukocyte iNOS is required for inflammation and pathological remodeling in ischemic heart failure (original) (raw)

2017, Basic research in cardiology

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 ~sevenfold higher cardiac M1 macrophages, which were primarily CCR2(-) cells. In contrast, as compared with WTc HF mice, iNOS(-/-)c HF mice exhibited significantly improved survival, LV function, hypertrophy, fibrosis, oxidativ...