Slow cardiac myosin regulatory light chain 2 (MYL2) was down-expressed in chronic heart failure patients

Abstract

Background: Genetic studies have shown that many slow cardiac myosin regulatory light chain 2 (MYL2) gene mutations can cause hypertrophic cardiomyopathy, which is one of the most common causes of heart failure (HF). But until now there has been no pathological or histological evidence that MYL2 may be associated with HF development. Recent microarray studies indicated that myosin heavy chain expression changed in the pathological process of HF. Because MYL2 is a regulatory component of myosin heavy polypeptide, the role of MYL2 protein in HF needs to be studied.

Hypothesis: The level of expression of MYL2 may change in the heart tissue of patients with chronic HF.

Methods: We collected 28 human right auricle samples, 16 from chronic HF patients and 12 from healthy control subjects. Immunohistochemistry was carried out to observe the tissue-expression pattern of the MYL2 protein and Western blot methods were performed to quantify the relative MYL2 expression level.

Results: In chronic HF patients, the MYL2 protein level decreased significantly compared with normal controls (t test P < 0.05). Among the 16 HF patients, MYL2 expression in the severe HF group (New York Heart Association [NYHA] class III or IV) was even lower than that of the moderate HF group (NYHA class II) (t test P < 0.05).

Conclusions: MYL2 was down-expressed in HF tissues, and our findings suggested that MYL2 may play a role in the development and progression of chronic HF.

Figure 1

IHC staining. Immunostain of MYL2 in 3 representative samples. View fields were 20× magnified. The brown areas indicate MYL2‐positive staining. The blue areas indicate cell nuclei. (A) Moderate HF patient A10 (NYHA class II); (B) severe HF patient B10 (NYHA class IV); (C) normal control individual C2; (D) IOD measurement of IHC images for each group. The asterisk represents the statistical significance level of P < 0.05 and the double asterisk represents the statistical significance level of P < 0.01. Abbreviations: HF, heart failure; IHC, immunohistochemistry; IOD, integrated optical density; MYL2, myosin regulatory light chain 2; NYHA, New York Heart Association

Figure 2

Western blot and quantification of MYL2 protein. MYL2 was down‐expressed in HF tissue. (A) Western blot result of 3 representative samples. A specific ∼20 kDa band was observed for MYL2 protein. For HF patients A10 and B10, MYL2 expression is decreased compared with the C2 normal control. (B) Quantification showed that in moderate HF (group A), severe HF (group B), and total HF patients (group A + B), the relative MYL2 levels were 80%, 60%, and 70%, respectively, of control group C. The asterisk represents the statistical significance level of P < 0.05 and the double asterisk represents the statistical significance level of P < 0.01. The y‐axis is the relative expression level (%). The average expression level of the control group was set as 100%. Abbreviations: HF, heart failure; MYL2, myosin regulatory light chain 2