Abstract
Sepsis and pneumonia are major causes of death in the United States, and their pathophysiology includes infection with inflammation and immune dysfunction. Both sepsis and pneumonia cause cardiovascular dysfunction. The expression of Osteopontin (OPN) in cardiomyocytes of patients with sepsis or pneumonia, and its role the induced cardiac dysfunction have not been thoroughly investigated. OPN is a matricellular protein synthesized by multiple diseased tissues and cells including cardiomyocytes. Here, we studied the expression of OPN protein using immunofluorescence in human myocardial autopsy tissues from pediatric and mid age or elderly patients with sepsis and/or pneumonia. Fourteen human myocardial tissues from six pediatric patients and eight mid-age or elderly patients were studied. Immunofluorescence was used to investigate the expression of OPN in paraffin-embedded heart sections co-stained with the myocyte markers Actin Alpha 1 (ACTA1) and Myosin Light Chain 2 (MLC2). A quantitative analysis was performed to determine the number of ACTA1 and MLC2 positive cardiomyocytes that express OPN. The results showed that OPN expression was significantly increased in cardiomyocytes in the hearts from pediatric patients with sepsis and/or pneumonia (N = 3) relative to pediatric patients without sepsis/pneumonia (N = 3), or adult to elderly patients with sepsis/pneumonia (N = 5). Among the older septic hearts, higher levels of cardiomyocyte OPN expression was seen only in conjunction with severe coronary arterial occlusion. This is the first study to document increased OPN expression in cardiomyocytes of pediatric subjects with sepsis or pneumonia. Our findings highlight a potentially important role for OPN in sepsis- or pneumonia-mediated cardiac dysfunction in pediatric patients.
Highlights
IntroductionOsteopontin (OPN) is a matricellular protein synthesized by a range of tissues and cell types including immunological cells (macrophages and T cells) (Lund et al, 2009), fibroblasts (Ashizawa et al, 1996; Jin et al, 2011), epithelial cells (Kato et al, 2014), osteoclasts, and osteoblasts (Qing et al, 2014), vascular smooth muscle cells (Sodhi et al, 2001), renal tubular epithelial cells (Zhang et al, 2010; Cobbs et al, 2018; Ding et al, 2018), and cardiomyocytes (Ashizawa et al, 1996; Lorenzen et al, 2015)
All myocardial tissues were co-stained with the myocyte markers Actin Alpha 1 (ACTA1) and Myosin Light Chain 2 (MLC2) to unequivocally identify the OPN positive cardiomyocytes
Our study shows that OPN expression was increased in cardiomyocytes of pediatric patients with sepsis or pneumonia but not in those of elderly patients without evidence of comorbid Coronary Artery Disease
Summary
Osteopontin (OPN) is a matricellular protein synthesized by a range of tissues and cell types including immunological cells (macrophages and T cells) (Lund et al, 2009), fibroblasts (Ashizawa et al, 1996; Jin et al, 2011), epithelial cells (Kato et al, 2014), osteoclasts, and osteoblasts (Qing et al, 2014), vascular smooth muscle cells (Sodhi et al, 2001), renal tubular epithelial cells (Zhang et al, 2010; Cobbs et al, 2018; Ding et al, 2018), and cardiomyocytes (Ashizawa et al, 1996; Lorenzen et al, 2015). Sepsis (Merx and Weber, 2007; Rudiger and Singer, 2007, 2013; Hunter and Doddi, 2010) and pneumonia (Corrales-Medina et al, 2011, 2012; Singanayagam et al, 2012; Brown et al, 2014) can compromise the heart causing myocardial dysfunction. The expression of OPN in cardiomyocytes of septic patients, and its role in sepsis-mediated cardiac dysfunction have not been studied
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