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. 2022 Jun 24;64:e45. doi: 10.1590/S1678-9946202264045

Table 2. NI = not informed.

- Characteristics of studies that evaluated Galectin-3 and myocardial fibrosis in Chagas chronic cardiopathy humans and mice.

Article Population description Comparative events Fibrosis detection/Galectin-3 detection Main results of Galectin-3 and fibrosis Correlation between Galectin-3 and fibrosis?
Cruz et al.14

  • n = 55

  • IF: 16

  • CF: 39

 Myocardial fibrosis in patients with and without Galectin-3 polymorphism, and myocardial fibrosis in subjects with AA, AC, and CC genotypes for gene variants at two Galectin-3 single nucleotide polymorphism (SNP) sites (rs4644 and rs4652) Magnetic r esonance imaging/RT-PCR

  • No significant difference in myocardial fibrosis between individuals with and without any of the rs4644 and rs4652 SNPs genotypes

  • The mean percentage of myocardial fibrosis was not statistically different between AA, AC, and CC genotypes (p = 0.508), or between SNP rs4644 and SNP rs4652 (p = 0.903)

 No correlation
Noya-Rabelo et al.15

  • n = 61

  • IF = 17

  • CF without ventricular dysfunction: 16

  • CF with ventricular dysfunction: 28

 Myocardial fibrosis and Galectin-3 plasma levels Magnetic r esonance imaging/ELISA

  • Myocardial fibrotic area

  • All subjects: 9.4% (2.4%–18.4%)

  • IF: 4,1% (2.1%–10.7%)

  • CF without ventricular dysfunction: 2.3% ( 1.0%–5.0%)

  • CF with ventricular dysfunction: 15.2% (7.8%–25%)

  • p = 0.004

  • Plasmatic concentration of Galectin-3

  • All subjects: 12.1 ng/mL (9.4–14.4 ng/mL)

  • IF: 12.1 ng/mL (8.8–18.3)

  • CF without ventricular dysfunction: 12.0 ng/mL (11.0–14.8 ng/mL)

  • CF with ventricular dysfunction: 12.0 ng/mL (11.0–14.8) p = 0.900

  • Correlation between Galectin-3 and myocardial fibrotic area ( r = 0.098; p = 0.47)

 No correlation
Echeverría et al.16

  • n = 100 (patients with Chagas cardiomyopathy; CCM)

  • Stage B (ECG abnormalities consistent with CCM and LVEF > 55%): 26

  • Stage C (ECG abnormalities consistent with CCM and LVEF 40%–55%): 29

  • Stage D (ECG abnormalities consistent with CCM and LVEF < 40%): n = 45

  • Galectin-3 concentration with ejection fraction left ventricular (LVEF) in three models:

  • Model 1 (crude odds ratio), model 2 (odds ratio adjusted for body mass index, age, sex, and estimated glomerular filtration rate), and model 3 (model 1 + further adjustment for angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blocker, aldosterone antagonist, and diuretic)

 LVEF/ELFA

  • Model 1

  • β =-0.421 (-0.618 to -0.224)

  • p < 0.001

Positive correlation
LVEF/ELFA

  • Model 2

  • β = -0.154 (-0.378 to 0.699)

  • p = 0.175

 No correlation
LVEF/ELFA

  • Model 3

  • β = -0.123 (-0.320 to 0.073)

  • p = 0.217

 No correlation
Ferrer et al.17

  • n = 15 Control mice infected by simulation (mock): 5

  • Mice infected with Trypanosoma. cruzi Hc strains (Hc): 5

  • Mice infected with T. cruzi Ac strains (Ac): 5

 Galectin-3 expression associated with cardiac extracellular matrix (ECM) remodeling of chronic murine cardiomyopathy through analysis of pro-collagen I mRNA levels RT-PCR and histopathology/immunohistochemistry

  • Analysis of procollagen I mRNA levels in samples from mice infected with Hc and

  • Ac Expression of procollagen I mRNA was higher in samples from animals inoculated with Ac (p < 0.05)

  • Histology of the heart inoculated with Hc and Ac

  • An increase in collagen matrix was observed in samples from animals infected with Hc and Ac. MEC remodeling was less intense in samples from mice inoculated with Hc compared to mice inoculated with Ac.

  • Expression of the Galectin-3 antigen in the hearts of animals infected with mock, Hc, or Ac

  • Significantly increased Galectin-3 levels were observed in samples from mice infected with Ac compared to the simulated controls (p < 0.001). Immunohistochemistry staining of the Galectin-3 antigen in the hearts of animals infected with mock, Hc, or Ac

  • Galectin-3 antigen was mainly detected in the cells located in the interstitium, and also at a higher level in the fibrotic areas.

 Positive correlation
Souza et al.18

  • n = 29

  • Mice not infected by T. cruzi (Naive): 8

  • Mice with infection times of 30 dpi (30 dpi): 5

  • Mice with infection times of 90 dpi (90 dpi): 5

  • Mice with infection times of 180 dpi (180 dpi): 11

 Galectin-3 expression and areas of fibrosis in cardiac sections of mice at different times of infection (30 dpi, 90 dpi, and 180 dpi) by T. cruzi Colombian strain Morphometric Analysis/ Immuno- fluorescence

  • Increased myocardial Galectin-3 cell expression compared to naïve controls by confocal microscopy.

  • Cardiac expression of Galectin-3 peaked at 30dpi but remained elevated during the chronic phase of infection compared to naive mice. Regarding the 30 dpi time for the naive mice, the p< 0.01, and 30 dpi for 180 dpi, the p< 0.001. The percentage of fibrosis increased with time.

  • Compared to the time of 180 dpi to 30 dpi p- < 0.001, and the time of 180 dpi to 90 dpi the p < 0.05.

 Positive correlation
Souza et al.19

  • Mouse model of CCC

  • Mice not infected by T. cruzi (naive)

  • Mice infected with T. cruzi with saline solution (saline)

  • Mice infected with T. cruzi with mesenchymal stromal cells controls (MSC-WT) .

  • Mice infected with T. cruzi with mesenchymal stromal cells

  • Galectin-3 knockdown (MSC-Gal3KD)

Area of fibrosis analyzed in cardiac sections and gene expression of collagen type I (Col1a1) in cardiac tissue of mice infected with saline T. cruzi, animals infected with T. cruzi control mesenchymal stromal cells (MSC-WT), and animals infected with T. cruzi knockdown mesenchymal stromal cells from Galectin-3 (MSC-Gal3KD). Morphometric Analysis/RT-PCR Analysis of cardiac sections in mice infected with T. cruzi showed extensive areas of fibrosis. While the fibrosis content in the heart was not altered between groups, collagen synthesis, as measured by gene expression of type I collagen (Col1a1), was reduced with wild-type MSC but not with Galectin-3 knockdown MSC. No correlations
Pineda et al.20

  • n = 10

  • Control mice: 5 Mice deficient in

  • Galectin-3 : 5

 Expression of collagen I, III, and IV and laminin in myocardial samples from C57BL/6 and Galectin-3 -/- mice, 28 and 60 days after T. cruzi infection Histopathology/ RT-PCR Reduced expression of collagen I, III, IV, and laminin in the hearts of Galectin-3 -/- infected animals compared to the control group Positive correlation

IF = Indeterminate form; CF = Cardiac form; ECG = electrocardiogram and echocardiogram; ECM = cardiac extracellular matrix; ELISA = enzyme-linked immunosorbent assay; ELFA = enzyme-linked fluorescence assay; Galectin-3 = galectin-3; LVEF = left ejection fraction left ventricular; dpi = days post-infection; RT-PCR = Real time-polymerase chain reaction.