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-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.