Modulation of Macrophage Polarization and HMGB1-TLR2/TLR4 Cascade Plays a Crucial Role for Cardiac Remodeling in Senescence-Accelerated Prone Mice

• Published in: PloS one 2016-04, Vol.11 (4), p.e0152922-e0152922
• Main Authors: Karuppagounder, Vengadeshprabhu, Giridharan, Vijayasree V, Arumugam, Somasundaram, Sreedhar, Remya, Palaniyandi, Suresh S, Krishnamurthy, Prasanna, Quevedo, Joao, Watanabe, Kenichi, Konishi, Tetsuya, Thandavarayan, Rajarajan A
• Format: Article
• Language: English
• Subjects: Aging; Aging - metabolism; Animals; Behavioral sciences; Biology and Life Sciences; Cardiovascular disease; CD36 antigen; Chronic illnesses; Comparative analysis; Cyclooxygenase 2 - metabolism; Cytokines; Differentiation; Genetic aspects; Geriatrics; Heart; Heart - physiology; Heart diseases; Heart failure; High mobility group proteins; HMGB1 protein; HMGB1 Protein - metabolism; Hypertension; Immune system; Immunoglobulins; Inflammation - metabolism; Interferon; Interleukin; Interleukin 10; Interleukin 6; Interleukin-10 - metabolism; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Ischemia; Kinases; Life sciences; Macrophages; Macrophages - metabolism; Male; Medicine and Health Sciences; Metabolism; Mice; NF-kappa B - metabolism; Oxidative stress; Pharmaceutical sciences; Pharmacology; Pharmacy; Physiological aspects; Polarization; Prostaglandin endoperoxide synthase; Proteins; Rodents; Senescence; Signal Transduction - physiology; Signaling; TLR2 protein; TLR4 protein; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Up-Regulation - physiology; Ventricular Remodeling - physiology; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0152922

The aim of this study was to investigate the role of macrophage polarization in aging heart. Macrophage differentiation is pathogenically linked to many inflammatory and immune disorders. It is often preceded by myocardial inflammation, which is characterized by increased cardiac damage and pro-inflammatory cytokine levels. Therefore, we investigated the hypothesis that senescence accelerated-prone (SAMP8) mice cardiac tissue would develop macrophage polarization compared with senescence-resistant control (SAMR1) mice. Both SAMP8 and SAMR1 mice were sacrificed when they became six month old. We evaluated, histo-pathological changes and modifications in protein expression by Western blotting and immuno-histochemical staining for M1 and M2 macrophage markers, high mobility group protein (HMG)B1 and its cascade proteins, pro-inflammatory factors and inflammatory cytokines in cardiac tissue. We observed significant upregulation of HMGB1, toll-like receptor (TLR)2, TLR4, nuclear factor (NF)κB p65, tumor necrosis factor (TNF)α, cyclooxygenase (COX)2, interferon (IFN)γ, interleukin (IL)-1β, IL-6 and M1 like macrophage specific marker cluster of differentiation (CD)68 expressions in SAMP8 heart. In contrast, M2 macrophage specific marker CD36, and IL-10 expressions were down-regulated in SAMP8 mice. The results from the study demonstrated that, HMGB1-TLR2/TLR4 signaling cascade and induction of phenotypic switching to M1 macrophage polarization in SAMP8 mice heart would be one of the possible reasons behind the cardiac dysfunction and thus it could become an important therapeutic target to improve the age related cardiac dysfunction.