The lectin Galectin-3 (Gal-3) is important in immune regulation. In both hypertensive rats and heart-failure patients, Gal-3 is also a marker for unfavorable prognosis. Nevertheless, the mechanism of Gal-3 action in hypertension-induced target organ damage is unknown. We hypothesized that in Ang II-induced hypertension, Gal-3 deficiency prevents left ventricular (LV) adverse remodeling and LV dysfunction by reducing immune responses and myocardial fibrosis. Male C57BL/6J and Gal-3 knockout (KO) mice were infused with Ang II for 8 weeks. We assessed: 1) systolic blood pressure (SBP) by plethysmography; 2) LV function and remodeling by echocardiography, 3) myocardial fibrosis by histology, 4) cardiac macrophage infiltration by histology, 5) ICAM-1 and VCAM-1 expression by Western blotting, 6) plasma cytokines by enzyme-linked immunosorbent assay, and 7) regulatory T cells (Treg) by flow cytometry detected by their combined expression of CD4, CD25, and FOXP3. SBP 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. These mice also had higher myocardial fibrosis and macrophage infiltration, higher cardiac ICAM-1 expression, as well as plasma IL-6. However, all these parameters were blunted in Gal-3KO mice. Hypertensive Gal-3KO mice also had a higher percentage splenic Treg lymphocytes. In conclusion, in Ang II-induced hypertension, Gal-3 genetic deletion prevented LV dysfunction without affecting the blood pressure or LV hypertrophy. This study indicates that the Ang II effects are partially mediated or triggered by Gal-3 together with related intercellular signaling, leading to cardiac inflammation and fibrosis.
- Angiotensin II
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology