Regulation of endothelial nitric oxide synthase in cardiac remodeling.

Abstract

OBJECTIVES:

Our previous study demonstrated that endothelial nitric oxide synthase (eNOS) gene serves as a candidate for modifiers of hypertrophic cardiomyopathy (HCM), which alters severity of HCM phenotypes. Herein, we sought to further elucidate the role of eNOS on cardiac myocyte hypertrophy and fibrosis, the major phenotypes of HCM.

METHODS:

Male eNOS-deficient mice (eNOS-/-) and wild type control mice (eNOS+/+, C57B1/6 J) were used in this study. Myocyte size was analyzed in hematoxylin/eosin stained sections using an image analyzing system. Cardiac β-myosin heavy chain (β-MHC) and α-skeletal actin (α-SKA) levels, markers of myocyte hypertrophy were evaluated by Western blot. Cardiac collagen volume fraction (CVF) was examined in picrosirius red stained section using an image analyzing system. Cardiac expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and transforming growth factor beta 1 (TGF-β1), markers of fibrosis, were determined by Western blot.

RESULTS:

Compared to eNOS+/+ mice, we found that; 1) myocyte size was significantly increased in eNOS-/- mice; 2) cardiac expression of β-MHC was markedly elevated, while α-SKA levels remained unchanged in eNOS-/- mice; 3) cardiac total and interstitial CVF levels were significantly higher in eNOS-/- mice; and 4) cardiac TIMP-1 levels were significantly greater in eNOS-/- mice, however, cardiac TGF-β1 was not differently expressed between the two groups.

CONCLUSION:

The current study revealed that eNOS plays a beneficial role in cardiac remodeling, preventing the heart from development of myocyte hypertrophy and cardiac fibrosis. These findings support our previous report that eNOS may modify the severity of HCM phenotypes.

• Authors: Meryl Musicante, Hannah H Kim, Yuanjian Chen, Fang Liao, Syamal K Bhattacharya, Lu Lu, Yao Sun
• Journal: International journal of cardiology (Int J Cardiol) Vol. 364 Pg. 96-101 (10 01 2022) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 35654172 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Tissue Inhibitor of Metalloproteinase-1
• Nitric Oxide
• Nitric Oxide Synthase Type III
• Nos3 protein, mouse

Topics

• Animals
• Cardiomyopathy, Hypertrophic (genetics)
• Fibrosis
• Hypertrophy
• Male
• Mice
• Mice, Knockout
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III
• Tissue Inhibitor of Metalloproteinase-1
• Ventricular Remodeling