Galectin-1 Protects Against Cardiac Fibrosis and Diastolic Dysfunction in Angiotensin II–Induced Hypertension

Background: Galectin-1 (Gal-1) is known to modulate inflammation and fibrosis. However, its role in hypertension-induced target organ damage (TOD) is unknown. We hypothesized that Gal-1 exerts a protective role against cardiac fibrosis and functions in a murine model of angiotensin II (ANG II)-induced hypertension. Methods: Male C57BL/6J and Gal1 knockout (KO) mice (n= 4–5) were infused subcutaneously with ANG II (3 μg·min - ¹·kg - ¹) for 4 weeks. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography while Left ventricular (LV) function and remodeling was assessed by echocardiography. Myocardial hypertrophy and fibrosis were assessed histologically. Antioxidant enzyme activity (catalase and superoxide dismutase) and matrix metalloproteinase (MMP-9) expression were evaluated by spectrophotometric assays and quantitative PCR (qPCR), respectively. Results: ANG II infusion increased SBP from 122 ± 5 and 112 ± 6 mmHg (baseline) to 158 ± 14 and 162 ± 11 mmHg in C57 and Gal1-KO mice (p < 0.05 vs baseline). Heart weight/tibia length (HW/TL mg/mm) increased in both hypertensive strains, although the difference between hypertensive genotypes was similar (p=NS). LV ejection fraction (LVEF) and fractional shortening (FS) were similar among the groups, indicating preserved systolic function. However, both hypertensive groups exhibited a significant increase in interventricular septal thickness during systole compared to their respective vehicle-treated controls, consistent with concentric hypertrophic remodeling (p < 0.01 for Gal-1 KO; p < 0.001 for C57 mice). E/A ratio was significantly decreased in hypertensive Gal1-KO mice (0.6 ± 0.05) as compared with hypertensive C57 (2.7 ± 0.4; p < 0.0001 vs Gal1-KO mice). Myocyte cross-sectional area (mm 2 ), was significantly increased in both hypertensive groups compared to their respective vehicle-treated controls (p < 0.001), reflecting ANG II induced cellular hypertrophy. Myocardial fibrosis (%) was more pronounced in hypertensive Gal-1 KO mice compared to C57 (9 ± 4% vs. 5 ± 2%, p< 0.05). Catalase activity was significantly reduced in hypertensive Gal-1 KO mice (32 ± 7 A.U.) compared to hypertensive C57 mice (37 ± 6 A.U.), indicating decreased antioxidant capacity in the absence of Gal-1. No significant differences in MMP-9 expression was found among the groups. In summary, Gal-1 prevents myocardial fibrosis and diastolic dysfunction in ANG II-induced hypertension. This protective role may be associated but not limited to the reduction of oxidative stress. Further studies are needed to deeply understand the role of Gal1 in target organ damage in hypertension. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.