Abstract
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.
Highlights
Aging is characterized by increase in the anticipation of death overtime associated with unique changes in phenotype [1]
The most important findings were as follows (a) aging heart enhances M1-like macrophage phenotype, HMGB1 cascade and inflammatory cytokine levels in SAMP8 mice. (b) Aging suppresses anti-inflammatory gene expression by switching M1 phenotype, leading to decreased CD36 and IL-10 protein levels in SAMP8 mice heart
It has likewise been indicated that SAMP8 mice develop myocardial damage and induce pro-inflammatory and inflammatory cytokines [18]
Summary
Aging is characterized by increase in the anticipation of death overtime associated with unique changes in phenotype [1]. By 2030, approximately 20% of the population will be older and incident coronary heart disease is projected to increase by approximately 26% in 2040 [2]. Rising of aging population is accompanied by a sharp increase in the prevalence of age-associated chronic diseases ranging from cardiovascular diseases (CVD), Alzheimer’s disease and cancer to metabolic syndrome [3]. CVD includes coronary artery disease, hypertension, and chronic heart failure and they are the leading cause of death worldwide. Reports stated that approximately 85% of CVD patients die at 65 years or older. Aging is associated with a dramatic growth in the prevalence of high blood pressure and chronic heart failure [4]. Since advancing age is such a crucial risk factor for the progress of this pathophysiological conditions, we used the senescence-accelerated prone mice (SAMP8), a murine model of spontaneous senescence that mimics many common geriatric disorders in the human population [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
