Nuclear Localization Leucine-Rich-Repeat Protein 1 Deficiency Protects Against Cardiac Hypertrophy by Pressure Overload.

Abstract

BACKGROUND/AIMS:

Nuclear localization leucine-rich-repeat protein 1 (NLRP1) is a cytoplasmic protein, involved in autoimmune diseases, mammalian reproduction, neuronal cell death, and stroke. However, the role of NLRP1 in cardiac hypertrophy remains unclear. We used in vivo and in vitro models to investigate the effects of NLRP1 on cardiac hypertrophy.

METHODS:

We used NLRP1-deficient mice and cultured neonatal rat cardiomyocytes with gain and loss of NLRP1 function. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements, and by pathological and molecular analysis.

RESULTS:

Eight weeks after aortic banding (AB), NLRP1 deficiency significantly inhibited aortic banding-induced cardiac hypertrophy, inflammation, and fibrosis. Activation of MAPK, NF-κB, and TGF-β/Smad pathways was reduced in NLRP1-knockout (KO) mice compared with that in wild-type (WT) mice. Consistent with these results, in vitro studies, performed using cultured neonatal mouse cardiomyocytes, confirmed that NLRP1 deficiency protects against cardiomyocyte hypertrophy induced by isoproterenol (PE); this protective activity was associated with the arrest of MAPK and NF-κB signaling.

CONCLUSIONS:

Our data illustrates that NLRP1 plays a crucial role in the development of cardiac hypertrophy via positive regulation of the MAPK, NF-κB, and TGF-β/Smad signaling pathways.

• Authors: Jing Zong, Fang-Fang Li, Kai Liang, Rui Dai, Hao Zhang, Ling Yan, Jia-Li Liu, Lu-Hong Xu, Wen-Hao Qian
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 48 Issue 1 Pg. 75-86 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 30001530 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• NALP1 protein, mouse
• NF-kappa B
• RNA, Small Interfering
• Natriuretic Peptide, Brain
• Atrial Natriuretic Factor
• Mitogen-Activated Protein Kinases
• Sarcoplasmic Reticulum Calcium-Transporting ATPases

Topics

• Adaptor Proteins, Signal Transducing (antagonists & inhibitors, genetics, metabolism)
• Animals
• Apoptosis Regulatory Proteins (antagonists & inhibitors, genetics, metabolism)
• Atrial Natriuretic Factor (metabolism)
• Cardiomegaly (chemically induced, pathology, prevention & control)
• Disease Models, Animal
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mitogen-Activated Protein Kinases (metabolism)
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (cytology, metabolism)
• NF-kappa B (metabolism)
• Natriuretic Peptide, Brain (metabolism)
• Pressure
• RNA Interference
• RNA, Small Interfering (metabolism)
• Rats
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (metabolism)
• Signal Transduction