title: Cardiac-deleterious role of galectin-3 in chronic angiotensin II-induced hypertension.
abstract: Galectin-3 (Gal-3), a member of the β-galactoside lectin family, has an important role in immune regulation. In hypertensive rats and heart failure patients, Gal-3 is considered a marker for an unfavorable prognosis. Nevertheless, the role and mechanism of Gal-3 action in hypertension-induced target organ damage are unknown. We hypothesized that, in angiotensin II (ANG II)-induced hypertension, genetic deletion of Gal-3 prevents left ventricular (LV) adverse remodeling and LV dysfunction by reducing the innate immune responses and myocardial fibrosis. To induce hypertension, male C57BL/6J and Gal-3 knockout (KO) mice were infused with ANG II (3 μg·min-1·kg-1sc) for 8 wk. We assessed: 1) systolic blood pressure by plethysmography, 2) LV function and remodeling by echocardiography, 3) myocardial fibrosis by histology, 4) cardiac CD68+macrophage infiltration by histology, 5) ICAM-1 and VCAM-1 expression by Western blotting, 6) plasma cytokines, including interleukin-6 (IL-6), by enzyme-linked immunosorbent assay, and 7) regulatory T (Treg) cells by flow cytometry as detected by their combined expression of CD4, CD25, and FOXP3. Systolic blood pressure and cardiac hypertrophy increased similarly in both mouse strains when infused with ANG II. However, hypertensive C57BL/6J mice suffered impaired ejection and shortening fractions. In these mice, the extent of myocardial fibrosis and macrophage infiltration was greater in histological sections, and cardiac ICAM-1, as well as plasma IL-6, expression was higher as assessed by Western blotting. However, all these parameters were blunted in Gal-3 KO mice. Hypertensive Gal-3 KO mice also had a higher number of splenic Treglymphocytes. In conclusion, in ANG II-induced hypertension, genetic deletion of Gal-3 prevented LV dysfunction without affecting blood pressure or LV hypertrophy. This study indicates that the ANG II effects are, in part, mediated or triggered by Gal-3 together with the related intercellular signaling (ICAM-1 and IL-6), leading to cardiac inflammation and fibrosis.
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.|Cardiovascular Pathophysiology Institute, Department of Pathology, University of Buenos Aires, Buenos Aires, Argentina; and.
authors: Germán E
authors: GE
authors: González
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.|Department of Physiology, Wayne State University, Detroit, Michigan.
authors: N-E
authors: NE
authors: Rhaleb
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors: Martin A
authors: MA
authors: D'Ambrosio
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors: Pablo
authors: P
authors: Nakagawa
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors: Tang-Dong
authors: TD
authors: Liao
authors: Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan.
authors: Edward L
authors: EL
authors: Peterson
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors: Pablo
authors: P
authors: Leung
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors: Xiangguo
authors: X
authors: Dai
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors: Branislava
authors: B
authors: Janic
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors: Yun-He
authors: YH
authors: Liu
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors: Xiao-Ping
authors: XP
authors: Yang
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan; ocarret1@hfhs.org.
authors: Oscar A
authors: OA
authors: Carretero
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001794:Blood Pressure; D015153:Blotting, Western; D006332:Cardiomegaly / Q000000981:diagnostic imaging* / Q000209:etiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis; D005434:Flow Cytometry; D037502:Galectin 3 / Q000235:genetics*; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010991:Plethysmography; D050378:T-Lymphocytes, Regulatory; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000209:etiology; D016277:Ventricular Function, Left; D000097382:CD68 Molecule
chemical_list: D000804:Angiotensin II; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016207:Cytokines; D037502:Galectin 3; D018799:Intercellular Adhesion Molecule-1; D019010:Vascular Cell Adhesion Molecule-1; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C090509:Icam1 protein, mouse
keywords: angiotensin II; fibrosis; galectin-3; hypertension; inflammation; interleukin-6; macrophages