Secreted miRNAs suppress atherogenesis.
ABSTRACT Endothelial-vascular smooth muscle cell communication has a critical role in cardiovascular homeostasis and the pathogenesis of atherosclerosis. A study now demonstrates extracellular-vesicle-mediated transfer of the atheroprotective microRNAs miR-143/145 between endothelial and vascular smooth muscle cells, providing compelling evidence that intercellular transport of miRNAs can influence a pathological process, namely atherosclerosis.
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ABSTRACT: Mesenchymal stem cells (MSCs) are adult multipotent cells that give rise to various cell types of the mesodermal germ layer. MSCs are of great interest in the field of regenerative medicine and cancer therapy because of their unique ability to home to damaged and cancerous tissue. These cells also regulate the immune response and contribute to reparative processes in different pathological conditions, including musculoskeletal and cardiovascular diseases. The use of MSCs for tissue repair was initially based on the hypothesis that these cells home to and differentiate within the injured tissue into specialized cells. However, it now appears that only a small proportion of transplanted MSCs actually integrate and survive in host tissues. Thus, the predominant mechanism by which MSCs participate in tissue repair seems to be related to their paracrine activity. Indeed, MSCs provide the microenvironment with a multitude of trophic and survival signals including growth factors and cytokines. Recent discoveries suggest that lipid microvesicles released by MSCs may also be important in the physiological function of these cells. Over the past few years the biological relevance of micro- and nano-vesicles released by cells in intercellular communication has been established. Alongside the conventional mediators of cell secretome, these sophisticated nanovesicles transfer proteins, lipids and, most importantly, various forms of RNAs to neighboring cells, thereby mediating a variety of biological responses. The physiological role of MSC-derived vesicles (MSC-MVs) is currently not well understood. Nevertheless, encouraging results indicate that MSC-MVs have similar protective and reparative properties as their cellular counterparts in tissue repair and possibly anti-cancer therapy. Thus, MSC-MVs represent a promising opportunity to develop novel cell-free therapy approaches that might overcome the obstacles and risks associated with the use of native or engineered stem cells.Frontiers in Physiology 09/2012; 3:359. DOI:10.3389/fphys.2012.00359 · 3.50 Impact Factor
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ABSTRACT: Abstract MicroRNAs (miRNAs) are now recognized as important post-transcriptional regulators of gene expression. MiRNAs are known to modulate cellular functions relevant to the normal and pathological physiology of the trabecular meshwork (TM) such as cell contraction and extracellular matrix turnover. There is also increasing evidence supporting the role of miRNAs in the pathogenesis of multiple diseases, and their potential value as both biomarkers of disease and therapeutic targets. However, compared with other tissues, our current knowledge regarding the roles played by miRNAs in the TM is still very limited. Here, we review the information currently available about miRNAs in the TM and discuss the main challenges and opportunities to incorporate the rapid progress in miRNA biology to the understanding of the normal and pathological physiology of the TM, and to develop novel clinical applications for diagnosis and therapy of high intraocular pressure.Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 01/2014; DOI:10.1089/jop.2013.0191 · 1.42 Impact Factor
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ABSTRACT: Atherosclerotic plaques are the main cause of life threatening clinical endpoints like myocardial infarction and stroke. To prevent these endpoints, the improved early diagnosis and treatment of vulnerable atherosclerotic vascular lesions is essential. Although originally applied for anticancer treatment, recent advances have also showed the considerable potential of nanotechnology for atherosclerosis. Otherwise, one domain of laboratory medicine is the investigation of new biomarkers. Recent research activities have identified the usability of biomarker-targeted nanoparticles for molecular imaging and pharmacologic modification of vulnerable atherosclerotic lesions leading to myocardial infarction or stroke. These investigations have established a new research interface between laboratory medicine, nanotechnology, cardiology/neurology, and radiology. In this review, we discuss inflammatory pathophysiologic mechanisms and biomarkers associated with a vulnerable atherosclerotic plaque phenotype. Further, we will emphasize cardiovascular relevant functionalized nanoparticle biomarker constructs which were developed within the cooperation interface between Laboratory Medicine (anti-inflammatory biomarkers), Nano-Medicine (nanoparticle development), and Radiology (molecular imaging).Clinica Chimica Acta 07/2014; 437. DOI:10.1016/j.cca.2014.06.029 · 2.76 Impact Factor