RIP2 deficiency attenuates cardiac hypertrophy, inflammation and fibrosis in pressure overload induced mice

Although the pathological cardiac hypertrophy presents a leading cause of morbidity and mortality worldwide, our knowledge of the molecular mechanisms underlying the disease is still poor. Here, we reported that receptor-interacting serine/threonine-protein kinase 2 (RIP2), promoting pro-inflammator...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2017-11, Vol.493 (2), p.1151-1158
Main Authors: Zhao, Cui-Hua, Ma, Xiang, Guo, Hong-Yu, Li, Peng, Liu, Hong-Yang
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
ACTIN
Animals
Aortic banding
BRAIN
Cardiac hypertrophy
Cardiomegaly - complications
Cardiomegaly - genetics
Cardiomegaly - pathology
COLLAGEN
DISEASE INCIDENCE
FIBROSIS
Gene Deletion
GENES
HEART
HYPERTROPHY
INFLAMMATION
Inflammation - complications
Inflammation - genetics
Inflammation - pathology
INHIBITION
INJURIES
KNOCK-OUT REACTIONS
LYMPHOKINES
Male
MICE
Mice, Inbred C57BL
Mice, Knockout
MORTALITY
MUSCLES
Myocardium - metabolism
Myocardium - pathology
MYOSIN
NECROSIS
NEOPLASMS
PEPTIDES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
Receptor-Interacting Protein Serine-Threonine Kinases - analysis
Receptor-Interacting Protein Serine-Threonine Kinases - genetics
RECEPTORS
RIP2
SERINE
SURGERY
THREONINE
Up-Regulation
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Summary:Although the pathological cardiac hypertrophy presents a leading cause of morbidity and mortality worldwide, our knowledge of the molecular mechanisms underlying the disease is still poor. Here, we reported that receptor-interacting serine/threonine-protein kinase 2 (RIP2), promoting pro-inflammatory gene expression, enhanced the pathological cardiac hypertrophy in animals. The effects of RIP2 on the cardiac hypertrophy triggered by pathological stimuli have not been fully investigated. In our study, mice were subjected to aortic banding (AB) surgery to explore the pathological, echocardiographic and molecular mechanisms. RIP2 expressed highly in cardiomyocytes after AB operation in wild type (WT) mice. RIP2-knockout (KO) attenuated cardiac hypertrophy, inflammation and fibrosis in mice 4 weeks after AB-surgery. First, RIP2 knockout down-regulated hypertrophic markers of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) in the heart of AB-operated mice.in addition, RIP2-deficiency reduced toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa B (TLR4/MyD88/NF-κB) activation, mitogen-activated protein kinases (MAPKs) phosphorylation and transforming growth factor-β1 (TGF-β1)/SMADs expressions, contributing to the suppression of inflammatory response and fibrosis, as further evidenced by down-regulated pro-inflammatory cytokines, including Tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-18, as well as fibrosis markers of Collagen I, Collagen III and α-smooth muscle actin (α-SMA). Taken together, our data indicated that RIP2-deficience ameliorated cardiac hypertrophy, inflammation and fibrosis through modulating multiple signaling pathways. •Overexpression of RIP2 contributed to development of hypertrophic heart.•RIP2-knockout attenuates cardiac injury and dysfunction in hypertrophic heart.•RIP2-deficience alleviates inflammation in heart of hypertrophic mice.•RIP2-deletion inhibits fibrosis in the heart of hypertrophic mice.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2017.07.035