Hypertrophic cardiomyopathy (HCM) is defined by the presence of ventricular hypertrophy in the absence of cardiac or systemic diseases that justify the development of this muscular alteration.1 It is the most common cardiopathy with a genetic cause, with an estimated prevalence of 0.2% (1:500).2^,3 Histologically, in addition to the hypertrophy and myocyte architecture disarray, varied increase in interstitial collagen and myocardial fibrosis occurs.4 Recent studies showed that fibrosis presence and extent are an independent predictor for the occurrence of sudden cardiac death (SCD) and progression to heart failure (HF) in these individuals.5^-9

Currently, Galectin-3 (Gal-3), a protein of the lectin family, has emerged as a new biomarker associated with myocardial fibrosis in acute and chronic heart failure (HF).10^,11 In the presence of inflammation, Gal-3 is secreted by activated macrophages, having the cardiac fibroblasts as binding sites, resulting in increased myocardial collagen expression and interstitial fibrosis.12^,13 Recent studies demonstrate the association between Gal-3 with inflammation and fibrosis, and these pathophysiological processes are related to adverse cardiac remodeling in HF.14^-16

The aim of the present study was to evaluate Gal-3 values ​​in patients with HCM and their association to myocardial fibrosis.

The study included 100 subjects divided into two groups, 50 HCM patients and 50 healthy control subjects. The groups were similar regarding age and gender (Table 1). The values found for serum Gal-3 measurements were low and showed no statistical differences between the two groups, HCM versus control, 10.3 ± 3.1 and 11.3 ± 2.6, p = 0.12 (Figure 1).

Figure 1

The patients with HCM were 72% males, with a mean age of 44 ± 12 years. All of them had preserved LVEF, mean septal thickness of 21.7 ± 5.2 mm and 29% had left ventricular outflow gradient > 30 mmHg at rest. Myocardial fibrosis was identified in 84% of these patients, and Gal-3 levels did not show any differences between the groups with present and absent myocardial fibrosis, 10.3 ± 3.4 and 10.1 ± 2.1, p = 0.59 (Table 2).

In the present study, serum Gal-3 levels were low and did not show any differences between patients with HCM and the control group. Myocardial fibrosis was a common finding, present in 84% of HCM patients, but Gal-3 values ​​also showed no differences between patients with and without fibrosis. Therefore, our findings suggest that other non-inflammatory mechanisms of myocardial structural remodeling are involved in the pathophysiology of fibrosis in this cardiopathy.

Galectin-3 is expressed by activated monocytes/macrophages and is involved in the regulation of inflammatory processes and pro-fibrotic pathways, acting as myocardial fibrosis mediator under conditions where necrosis and/or cellular apoptosis and consequent inflammatory reactions occur, described as a pathway of reparative fibrosis.12^,16 However, another collagen synthesis mechanism is known: the reactive pathway, in which fibrosis formation would be secondary to the neurohumoral activation without cardiomyocyte necrosis, with the following cellular mediators: angiotensin II, aldosterone and endothelin-1.17^-19

In patients with HCM, cardiac fibrosis is associated with adverse left ventricular remodeling, arrhythmias and worse prognosis. Currently, it is not known what factors decisively contribute to accelerate collagen deposition between the hypertrophied myocardial fibers in patients with HCM, and different causal mutations are thought to play an important role, as well as other genetic polymorphisms and environmental factors.20^-22

Kim et al.,23 demonstrated in an experimental study that myocardial fibrosis occurs independently of cell damage and inflammation in this heart disease. When analyzing the hearts of transgenic mice with a cardiac beta-myosin mutation, in which hypertrophy had not yet developed, they reported the early activation of potent fibrosis regulatory pathways and collagen deposition, despite normal cardiac histological findings, demonstrating the existence of a pro-fibrotic environment even before the disease onset.23 Thus, they corroborate our results, with low serum concentrations of Gal-3 and absence of an association with myocardial fibrosis.

The study by Hu et al.,24 aimed to determine the prognosis of myocardial fibrosis associated with Gal-3 levels in patients with non-ischemic cardiomyopathy. The sample consisted of 105 patients with HCM, with an older mean age than that in our study, 52 ± 15 years, and they identified that the association of Gal-3 with fibrosis showed a more significant prognostic value. However, when evaluating serum levels of Gal-3 in patients with HCM with and without fibrosis, they also did not find any significant differences.24

The findings of the present study contribute to the knowledge of the mechanisms involved in myocardial fibrosis formation in HCM, guiding future lines of research aimed at studying the formation of fibrosis and ventricular remodeling and modifying the natural history of the disease.

In patients with HCM, the serum concentration of Gal-3 is low and is not associated with the presence of myocardial fibrosis, suggesting that the reparative pathway of fibrosis formation is little activated in this cardiopathy.