PTX3: an inflammatory protein modulating ultrastructure and bioenergetics of human endothelial cells
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PTX3: an inflammatory protein modulating ultrastructure and bioenergetics of human endothelial cells Albino Carrizzo1, Claudio Procaccini2,3, Paola Lenzi4, Clorinda Fusco5, Francesco Villa6, Serena Migliarino7, Massimiliano De Lucia1, Francesco Fornai1,4, Giuseppe Matarese2,5, Annibale A. Puca6,8 and Carmine Vecchione1,8*
Abstract Background: Pentraxin 3 (PTX3), an acute-phase inflammation protein produced by several cell types, has long been described as a possible biomarker for age-related cardiovascular and cerebrovascular diseases. Although several mechanisms of action have been identified to date in the vascular and immune systems, the direct effects of PTX3 on isolated endothelial cells at morphological and metabolic levels remain unknown. Findings: PTX3 induced cytoplasmic vacuolization and dilution of mitochondrial matrix in isolated, human endothelial cells. Moreover, metabolic assays revealed that PTX3 increases respiratory capacity in support of mitochondrial function, and partially sustains the glycolytic pathway. Conclusions: PTX3 has, per se, a direct action on ultrastructural and bioenergetic parameters of isolated endothelial cells. This finding can be associated with our previous demonstration of a deleterious effect of PTX3 on the endothelial layer. More studies are needed to clearly demonstrate any direct correlation between these ultrastructural and bioenergetic changes with endothelial dysfunction, especially with regard to age-related cerebro- and cardio-vascular diseases. Keywords: Pentraxin 3, Endothelial cells, Mitochondria, Bioenergetics
Introduction In the last decade, several inflammatory mediators have been implicated in the pathogenesis of age-related cerebro- and cardio-vascular disorders [1–3]. Moreover, the growing body of studies linking inflammation to endothelial activation and loss of nitric oxide bioactivity has promoted investigators to seek evidence on the possible correlation of acute-phase proteins with endothelial-specific alterations [4, 5]. On this point, an elevated level of circulating Pentraxin 3 (PTX3) – a member of a protein superfamily involved in the innate immune response – has been described as a marker of poor prognosis in patients with stable coronary artery disease or heart failure [6–8]. Other studies have reported that PTX3 levels are higher in women with preeclampsia, speculating on its contribution to endothelial dysfunction [9]. Recently, we * Correspondence: [email protected] 1 Vascular Pathophysiology Unit, IRCCS Neuromed, 86077 Pozzilli, IS, Italy 8 Department of Medicine and Surgery, University of Salerno, Via S. Allende, 84081 Baronissi, SA, Italy Full list of author information is available at the end of the article
have reported that PTX3 is directly implicated in the pathogenesis of vascular endothelial dysfunction, through a P-selectin/matrix metalloproteinase-1 pathway [10], demonstrating that the exposure of mouse mesenteric arteries to PTX3 leads to alterations of vascular ultrastructural and impairment of nitr
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