Guerra Jepsen (yamcrow5)

Registration URL https//; Unique identifier NCT02948777. Our aim was to characterize distinctive clinical antiphospholipid syndrome phenotypes and identify novel microRNA (miRNA)-mRNA-intracellular signaling regulatory networks in monocytes linked to cardiovascular disease. Approach and Results Microarray analysis in antiphospholipid syndrome monocytes revealed 547 differentially expressed genes, mainly involved in inflammatory, cardiovascular, and reproductive disorders. Besides, this approach identified several genes related to inflammatory, renal, and dermatologic diseases. selleckchem Functional analyses further demonstrated phosphorylation of intracellular kinases related to thrombosis and immune-mediated chronic inflammation. miRNA profiling showed altered expression of 22 miRNAs, enriched in pathways related to immune functions, cardiovascular disease, and autoimmune-associated pathologies. Unbiased integrated mRNA-miRNA analysis identified a signature of 9 miRNAs as potential modulators of 17 interconnected genes related to cardiovascular disease. The altered expresssclerosis). Extensive molecular profiling of monocytes in patients with primary antiphospholipid syndrome might help to identify distinctive clinical phenotypes, thus enabling new patients' tailored treatments. Extensive molecular profiling of monocytes in patients with primary antiphospholipid syndrome might help to identify distinctive clinical phenotypes, thus enabling new patients' tailored treatments. Circulating progenitor cells possess vasculogenesis property and participate in repair of vascular injury. Cx (connexin) 43-a transmembrane protein constituting gap junctions-is involved in vascular pathology. However, the role of Cx43 in smooth muscle progenitor cells (SPCs) remained unclear. Approach and Results Human SPCs cultured from CD34 peripheral blood mononuclear cells expressed smooth muscle cell markers, such as smooth muscle MHC (myosin heavy chain), nonmuscle MHC, calponin, and CD140B, and Cx43 was the most abundant Cx isoform. To evaluate the role of Cx43 in SPCs, short interference RNA was used to knock down Cx43 expression. Cellular activities of SPCs were reduced by Cx43 downregulation. In addition, Cx43 downregulation attenuated angiogenic potential of SPCs in hind limb ischemia mice. Protein array and ELISA of the supernatant from SPCs showed that IL (interleukin)-6, IL-8, and HGF (hepatocyte growth factor) were reduced by Cx43 downregulation. Simultaneously, Cx43 downregulation reducedjunction protein Cx43 plays an important role in regulating cellular function and paracrine effects of SPCs through FAK-Src axis. Atherosclerotic lesions are often characterized by accumulation of OxLDL (oxidized low-density lipoprotein), which is associated with vascular inflammation and lesion vulnerability to rupture. Extracellular AIBP (apolipoprotein A-I binding protein; encoded by gene), when secreted, promotes cholesterol efflux and regulates lipid rafts dynamics, but its role as an intracellular protein in mammalian cells remains unknown. The aim of this work was to determine the function of intracellular AIBP in macrophages exposed to OxLDL and in atherosclerotic lesions. Approach and Results Using a novel monoclonal antibody against human and mouse AIBP, which are highly homologous, we demonstrated robust AIBP expression in human and mouse atherosclerotic lesions. We observed significantly reduced autophagy in bone marrow-derived macrophages, isolated from compared with wild-type mice, which were exposed to OxLDL. In atherosclerotic lesions from mice subjected to knockdown and fed a Western diet, autophagy waell death in the context of atherosclerosis. Low muscle mass was known to be associated with cardiovascular diseases. However, only few studies investigated the association between muscle quality and subclinical coronary atheros