Galectin-3 inhibition attenuates doxorubicin-induced cardiac dysfunction by upregulating the expression of peroxiredoxin-4.

Doxorubicin (DOX) is a highly efficient chemotherapeutic drug limited by its cardiotoxicity. Galectin-3 (Gal-3) overexpression is associated with several cardiovascular diseases. In this study, the in vivo models of DOX-treated rats and the in vitro model of DOX-treated H9C2 cells were used. DOX induced cardiac injury and dysfunction accompanied with the upregulation of Gal-3 at the end of the experiment, while inhibition of Gal-3 with modified citrus pectin (MCP) exhibited a dramatic improvement in cardiac function of the DOX-treated rats, as manifested by increased left ventricular systolic pressure and ±dp/dtmax and decreased left ventricular end-diastolic pressure. The plasma levels of myocardial injury markers such as lactate dehydrogenase, creatine kinase, creatine kinase-MB, and cardiac troponin I were decreased after MCP treatment. In parallel, MCP attenuated myocardial tissue markers of oxidative stress such as hydrogen peroxide and malondialdehyde restored the activities of superoxide dismutase, catalase, and glutathione peroxidase and upregulated antioxidant peroxiredoxin-4 (Prx-4). To further verify the role of Prx-4, it was downregulated by siRNA-mediated knockdown in H9C2 cells. MCP could not reverse DOX-induced oxidative stress in Prx-4-knock-down cells. In conclusion, Gal-3 mediated DOX-induced cardiotoxicity and Gal-3 inhibition attenuated DOX-induced cardiac dysfunction by upregulating the expression of Prx-4 to reduce myocardial oxidative stress.

Galectin-3 mediates high-glucose-induced cardiomyocyte injury by the NADPH oxidase/reactive oxygen species pathway.

Galectin-3 is a member of the ß-galactoside-binding lectin family taking part in the regulation of inflammation, angiogenesis, and fibrosis. This study was designed to study the improved effect of galectin-3 inhibition on diabetic cardiomyopathy (DCM). Sprague-Dawley rats were randomized into the control, DCM, and DCM + modified citrus pectin (MCP) (a galectin-3 pharmacological inhibitor) groups. After 8 weeks, streptozotocin-induced DCM led to high blood glucose level, oxidative stress, cardiac injury, and dysfunction accompanied by suppressed body mass. On the contrary, MCP (100 mg·kg-1·day-1) administration improved body mass and blood glucose level and attenuated cardiac injury and dysfunction in DCM rats. Additionally, MCP attenuated pathological changes in plasma and myocardial tissue markers of oxidative stress, such as hydrogen peroxide and malonyldialdehyde, although it did not change superoxide dismutase activities, which were decreased in the DCM group. The levels of oxidative stress associated proteins evaluated by Western blot, such as p67phox and NADPH oxidase 4, were obviously increased in the DCM group, while they were reversed by MCP treatment. Therefore, galectin-3-mediated high-glucose-induced cardiomyocyte injury and galectin-3 inhibition attenuated DCM by suppressing NADPH oxidase. These findings suggested that galectin-3 could be a potential target for treatment of patients with DCM.

Extracellular galectin-1 enhances adhesion to and invasion of oral epithelial cells by Porphyromonas gingivalis.

Galectin-1 and galectin-3 are C-type lectin receptors that bind to lipopolysaccharide in the cell wall of gram-negative bacteria. In this study, we investigated the effects of galectin-1 and galectin-3 on adhesion to and invasion of the human gingival epithelial cell line Ca9-22 by Porphyromonas gingivalis, a periodontal pathogenic gram-negative bacterium. Recombinant galectin-1, but not galectin-3, enhanced P. gingivalis adhesion and invasion, although both galectins bound similarly to P. gingivalis. Flow cytometry also revealed that Ca9-22 cells express low levels of galectin-1 and moderate levels of galectin-3. Ca9-22 cells in which galectin-3 was knocked-down did not exhibit enhanced P. gingivalis adhesion and invasion. Similarly, specific antibodies to galectin-1 and galectin-3 did not inhibit P. gingivalis adhesion and invasion. These results suggest that soluble galectin-1, but not galectin-3, may exacerbate periodontal disease by enhancing the adhesion to and invasion of host cells by periodontal pathogenic bacteria.

Modified citrus pectin stops progression of liver fibrosis by inhibiting galectin-3 and inducing apoptosis of stellate cells.

Modified citrus pectin (MCP) is a pH modified form of the dietary soluble citrus peel fiber known as pectin. The current study aims at testing its effect on liver fibrosis progression. Rats were injected with CCl4 (1 mL/kg, 40% v/v, i.p., twice a week for 8 weeks). Concurrently, MCP (400 or 1200 mg/kg) was administered daily in drinking water from the first week in groups I and II (prophylactic model) and in the beginning of week 5 in groups III and IV (therapeutic model). Liver function biomarkers (ATL, AST, and ALP), fibrosis markers (laminin and hyaluronic acid), and antioxidant biomarkers (reduced glutathione (GSH) and superoxide dismutase (SOD)) were measured. Stained liver sections were scored for fibrosis and necroinflammation. Additionally, expression of galectin-3 (Gal-3), α-smooth muscle actin (SMA), tissue inhibitor metalloproteinase (TIMP)-1, collagen (Col)1A1, caspase (Cas)-3, and apoptosis related factor (FAS) were assigned. Modified pectin late administration significantly (p < 0.05) decreased malondialdehyde (MDA), TIMP-1, Col1A1, α-SMA, and Gal-3 levels and increased levels of FAS, Cas-3, GSH, and SOD. It also decreased percentage of fibrosis and necroinflammation significantly (p < 0.05). It can be concluded that MCP can attenuate liver fibrosis through an antioxidant effect, inhibition of Gal-3 mediated hepatic stellate cells activation, and induction of apoptosis.

Post-marathon Decline in Right Ventricular Radial Motion Component Among Amateur Sportsmen.

Moderate physical activity has a positive impact on health, although extreme forms of sport such as marathon running may trigger exercise-induced cardiac fatigue. The explicit distinction between the right ventricular (RV) physiological response to training and maladaptive remodeling has not yet been determined. In this study, we aimed to analyze the impact of running a marathon on RV mechanics in amateur athletes using three-dimensional (3D) echocardiography (ECHO) and the ReVISION method (RV separate wall motion quantification). A group of 34 men with a mean age of 40 ± 8 years who successfully finished a marathon underwent ECHO three times, i.e., 2 weeks before the marathon (stage I), at the marathon finish line (stage II), and 2 weeks after the marathon (stage III). The ECHO findings were then correlated with the concentrations of biomarkers related to myocardial injury and overload and also obtained at the three stages. On finishing the marathon, the amateur athletes were found to have a significant (p < 0.05) increase in end-diastolic (with a median of 51.4 vs. 57.0 ml/m2) and end-systolic (with a median of 24.9 vs. 31.5 ml/m2) RV volumes indexed to body surface area, reduced RV ejection fraction (RVEF) (with a median of 51.0% vs. 46.0%), and a decrease in RV radial shortening [i.e., radial EF (REF)] (with a mean of 23.0 ± 4.5% vs. 19.3 ± 4.2%), with other RV motion components remaining unchanged. The post-competition decrease in REF was more evident in runners with larger total volume of trainings (R 2 = 0.4776, p = 0.0002) and higher concentrations of high-sensitivity cardiac troponin I (r = 0.43, p < 0.05) during the preparation period. The decrease in REF was more prominent in the training of marathoners more than 47 km/week. At stage II, marathoners with a more marked decrease in RVEF and REF had higher galectin-3 (Gal-3) levels (r = -0.48 and r = -0.39, respectively; p < 0.05). Running a marathon significantly altered the RV performance of amateur athletes. Transient impairment in RV systolic function resulted from decreased radial shortening, which appeared in those who trained more extensively. Observed ECHO changes correlated with the concentrations of the profibrotic marker Gal-3.

Gender-Related Differences in Heart Failure Biomarkers.

Important differences in comorbidities and clinical characteristics exist between women and men with heart failure (HF). In particular, differences in the kinetics of biological circulating biomarkers-a critical component of cardiovascular care-are highly relevant. Most circulating HF biomarkers are assessed daily by clinicians without taking sex into account, despite the multiple gender-related differences observed in plasma concentrations. Even in health, compared to men, women tend to exhibit higher levels of natriuretic peptides and galectin-3 and lower levels of cardiac troponins and the cardiac stress marker, soluble ST2. Many biological factors can provide a reliable explanation for these differences, like body composition, fat distribution, or menopausal status. Notwithstanding, these sex-specific differences in biomarker levels do not reflect different pathobiological mechanisms in HF between women and men, and they do not necessarily imply a need to use different diagnostic cut-off levels in clinical practice. To date, the sex-specific prognostic value of HF biomarkers for risk stratification is an unresolved issue that future research must elucidate. This review outlines current evidence regarding gender-related differences in circulating biomarkers widely used in HF, the pathophysiological mechanisms underlying these differences, and their clinical relevance.

Evaluation of galectin-3 levels in acute coronary syndrome.

Galectin-3 is a new biomarker that is assumed to reflect fibrogenesis and inflammation. In this study, we aimed to evaluate the levels of galectin-3 in patients with acute coronary syndrome (ACS) and the relation of galectin-3 to the burden of atherosclerosis. Nineteen patients with ACS who underwent coronary angiography and 17 age-matched healthy controls were enrolled. The burden of atherosclerosis was assessed with Gensini score and with the number of involved vessels. Galectin-3 levels were measured on admission by using ELISA. The mean age of the cohort was 62.8±10.6 and 56% of the patients were male. Compared to control group, median galectin-3 levels were significantly higher in ACS patients (0.77ng/mL [0.50-1.19] vs. 0.51ng/mL [0.41-0.78], P=0.01). Patients were classified into three groups according to the number of involved vessels. Median galectin-3 levels did not differ significantly among groups (one vessel: 0.68ng/mL [0.55-0.74], two vessels: 0.67ng/mL [0.46-1.84], three vessels 0.90ng/mL [0.53-1.38], P=0.62). There was a strong correlation between galectin-3 levels and Gensini score (r=0.625, P=0.004). In conclusion, galectin-3 levels were elevated in patients with ACS and there was a strong correlation between galectin-3 levels and Gensini score.

Circulating microribonucleic acids miR-1, miR-21 and miR-208a in patients with symptomatic heart failure: Preliminary results.

BACKGROUND: Cardiomyocytes produce a wide variety of bioactive molecules that regulate numerous physiological and pathophysiological processes. Recently, it has been recognized that changes in microribonucleic acid (miRNA) expression may lead to cardiac dysfunction. AIMS: To assess the expression of circulating miRNAs (miR-1, miR-21 and miR-208a) in patients with symptomatic heart failure (HF), and to investigate the relationship between expression of these miRNAs and secretion of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and galectin-3. METHODS: Thirty-five patients in New York Heart Association (NYHA) class II/III (age: 68.8 ± 13.0 years) and 26 patients in NYHA class IV (age: 72.0 ± 10.4 years) hospitalized in the intensive coronary care unit participated in the study. Serum concentrations of miRNAs were measured by quantitative real-time polymerase chain reaction. Basic biochemical assays were carried out, and NT-proBNP and galectin-3 concentrations were measured in all serum samples. RESULTS: miR-1 was downregulated in patients with symptomatic HF and its expression decreased with severity of NYHA class (P=0.007). In contrast, overexpression of miR-21 was seen in all patients, independent of HF severity. Results suggest no miR-208a leakage into the circulation in patients with symptomatic HF. There was an inverse relationship between miR-1 expression and NT-proBNP concentration (Spearman's rank correlation coefficient [r]=-0.389; P=0.023) in patients in NYHA class II/III. Overexpression of miR-21 correlated significantly with galectin-3 concentration (r=0.422; P=0.032). CONCLUSION: Dysregulation of miR-1 and miR-21 expression may be essential for the development of HF; miR-1 might become a biomarker for predicting HF exacerbation.

[Impact of plasma pro-B-type natriuretic peptide amino-terminal and galectin-3 levels on the predictive capacity of the LIPID Clinical Risk Scale in stable coronary disease]. / Impacto de los niveles plasmáticos de pro-péptido natriurético tipo B aminoterminal, proteína quimiotáctica de monocitos-1 y galectina3 en la capacidad predictiva de eventos de la escala clínica LIPID en la enfermedad coronaria estable.

INTRODUCTION: At present, there is no tool validated by scientific societies for risk stratification of patients with stable coronary artery disease (SCAD). It has been shown that plasma levels of monocyte chemoattractant protein-1 (MCP-1), galectin-3 and pro-B-type natriuretic peptide amino-terminal (NT-proBNP) have prognostic value in this population. OBJECTIVE: To analyze the prognostic value of a clinical risk scale published in Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study and determining its predictive capacity when combined with plasma levels of MCP-1, galectin-3 and NT-proBNP in patients with SCAD. METHODS AND RESULTS: A total of 706 patients with SCAD and a history of acute coronary syndrome (ACS) were analyzed over a follow up period of 2.2 ± 0.99 years. The primary endpoint was the occurrence of an ischemic event (any SCA, stroke or transient ischemic attack), heart failure, or death. A clinical risk scale derived from the LIPID study significantly predicted the development of the primary endpoint, with an area under the ROC curve (Receiver Operating Characteristic) of 0.642 (0.579 to 0.705); P<0.001. A composite score was developed by adding the scores of the LIPID and scale decile levels of MCP -1, galectin -3 and NT-proBNP. The predictive value improved with an area under the curve of 0.744 (0.684 to 0.805); P<0.001 (P=0.022 for comparison). A score greater than 21.5 had a sensitivity of 74% and a specificity of 61% for the development of the primary endpoint (P<0.001, log -rank test). CONCLUSION: Plasma levels of MCP-1, galectin -3 and NT-proBNP improve the ability of the LIPID clinical scale to predict the prognosis of patients with SCAD.