Key result
Hypertrophic obstructive cardiomyopathy was associated with significantly increased SMAD2 and SMAD3 expressions and decreased SMAD7 expression, contributing to severe myocardial fibrosis.
Why the study?
HOCM brings a high risk of sudden cardiac death in young people, making it urgent to understand its development and mechanism to prevent unsafe incidents.
Are SMAD signaling proteins abnormally expressed in the myocardial tissue of pediatric and adult patients with hypertrophic obstructive cardiomyopathy?
Case-Control (n=26)
No
Are SMAD signaling proteins abnormally expressed in the myocardial tissue of pediatric and adult patients with hypertrophic obstructive cardiomyopathy?
Abnormal regulation of the SMAD signaling pathway, characterized by increased SMAD2/3 and decreased SMAD7, contributes to severe myocardial fibrosis in HOCM starting in childhood and persisting into adulthood.
Answers are grounded in this paper and cite their sources.
SMAD dysregulation may underlie fibrosis in pediatric and adult HOCM; hypothesis-generating and warrants prospective validation.
Hypertrophic obstructive cardiomyopathy (HOCM) can bring a high risk of sudden cardiac death in young people. It is particularly urgent to understand the development and mechanism of HOCM to prevent unsafe incidents. Here, the comparison between pediatric and adult patients with HOCM has been performed to uncover the signaling mechanism regulating pathological process through histopathological analysis and immunohistochemical analysis. We found SMAD proteins played an important role during myocardial fibrosis for HOCM patients. In patients with HOCM, Masson and HE staining showed that myocardial cells were diffusely hypertrophied with obvious disorganized myocardial fiber alignment, and myocardial tissue was more damaged and collagen fibers increased significantly, which come early in childhood. Increased expressions of SMAD2 and SMAD3 contributed to myocardial fibrosis in patients with HOCM, which happened early in childhood and continued through adulthood. In addition, decreased expression of SMAD7 was closely related to collagen deposition, which negatively expedited fibrotic responses in patients with HOCM. Our study indicated that the abnormal regulation of SMAD signaling pathway can lead to severe myocardial fibrosis in childhood and its fibrogenic effects persist into adulthood, which is a crucial factor in causing sudden cardiac death and heart failure in HOCM patients.
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Zhang et al. (2023) conducted a case-control in Hypertrophic obstructive cardiomyopathy (n=26). Hypertrophic obstructive cardiomyopathy vs. Autopsy individuals who died of non-cardiac disease was evaluated on SMAD2 expression in adult ventricular septal myocardial tissue (IOD) (p=0.0001). Hypertrophic obstructive cardiomyopathy was associated with significantly increased SMAD2 and SMAD3 expressions and decreased SMAD7 expression, contributing to severe myocardial fibrosis.
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