1,721,046 research outputs found
C-reactive protein: a potential new molecular link between imflammation, thrombosis and vascular cell proliferation?
No full textOsteogenic differentiation of amniotic fluid mesenchymal stromal cells and their bone regeneration potential
Full text linkIn orthopedics, tissue engineering approach using stem cells is a valid line of treatment for patients with bone defects. In this context, mesenchymal stromal cells of various origins have been extensively studied and continue to be a matter of debate. Although mesenchymal stromal cells from bone marrow are already clinically applied, recent evidence suggests that one may use mesenchymal stromal cells from extra-embryonic tissues, such as amniotic fluid, as an innovative and advantageous resource for bone regeneration. The use of cells from amniotic fluid does not raise ethical problems and provides a sufficient number of cells without invasive procedures. Furthermore, they do not develop into teratomas when transplanted, a consequence observed with pluripotent stem cells. In addition, their multipotent differentiation ability, low immunogenicity, and anti-inflammatory properties make them ideal candidates for bone regenerative medicine. We here present an overview of the features of amniotic fluid mesenchymal stromal cells and their potential in the osteogenic differentiation process. We have examined the papers actually available on this regard, with particular interest in the strategies applied to improve in vitro osteogenesis. Importantly, a detailed understanding of the behavior of amniotic fluid mesenchymal stromal cells and their osteogenic ability is desirable considering a feasible application in bone regenerative medicine
High glucose, nitric oxide, and adenosine: a vicious circle in chronic hyperglycaemia?
No full textThis editorial refers to ‘Nitric oxide reduces SLC29A1 promote activity and adenosine transport involving transcription factor complex hCHOP–C/EBPa in human umbilical vein endothelial cells from gestational diabetes’ by M. Farı ́as et al., pp. 45–54, this issue
Chronic hyperglicemia and nitric oxide bioavailability play a pivotal role in pro-atherogenic vascular modifications.
No full textDiabetes is associated with accelerated atherosclerosis and macrovascular complications are a major cause of morbidity and mortality in this disease. Although our understanding of vascular pathology has lately greatly improved, the mechanism(s) underlying enhanced atherosclerosis in diabetes remain unclear. Endothelial cell dysfunction is emerging as a key component in the pathophysiology of cardiovascular abnormalities associated with diabetes. Although it has been established that endothelium plays a critical role in overall homeostasis of the vessels, vascular smooth muscle cells (vSMC) in the arterial intima have a relevant part in the development of atherosclerosis in diabetes. However, high glucose induced alterations in vSMC behaviour are not fully characterized. Several studies have reported that impaired nitric oxide (NO) synthesis and/or actions are often present in diabetes and endothelial dysfunction. Furthermore, although endothelial cells are by far the main site of vascular NO synthesis, vSMC do express nitric oxyde synthases (NOSs) and NO synthesis in vSMC might be important in vessel's function. Although it is known that vSMC contribute to vascular pathology in diabetes by their change from a quiescent state to an activated proliferative and migratory phenotype (termed phenotypic modulation), whether this altered phenotypic modulation might also involve alterations in the nitrergic systems is still controversial. Our recent data indicate that, in vivo, chronic hyperglycemia might induce an increased number of vSMC proliferative clones which persist in culture and are associated with increased eNOS expression and activity. However, upregulation of eNOS and increased NO synthesis occur in the presence of a marked concomitant increase of O(2-) production. Since NO bioavailabilty might not be increased in high glucose stimulated vSMC, it is tempting to hypothesize that the proliferative phenotype observed in cells from diabetic rats is associated with a redox imbalance responsible quenching and/or trapping of NO, with the consequent loss of its biological activity. This might provide new insight on the mechanisms responsible for accelerated atherosclerosis in diabetes
Physiology and pathophysiology of oxLDL uptake by vascular wall cells in atherosclerosis
Full text linkAtherosclerosis is a progressive disease in which endothelial cell dysfunction, macrophage foam cell formation, and smooth muscle cell migration and proliferation, lead to the loss of vascular homeostasis. Oxidized low-density lipoprotein (oxLDL) may play a pre-eminent function in atherosclerotic lesion formation, even if their role is still debated. Several types of scavenger receptors (SRs) such as SR-AI/II, SRBI, CD36, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), toll-like receptors (TLRs) and others can promote the internalization of oxLDL. They are expressed on the surface of vascular wall cells (endothelial cells, macrophages and smooth muscle cells) and they mediate the cellular effects of oxLDL. The key influence of both oxLDL and SRs on the atherogenic process has been established in atherosclerosis-prone animals, in which antioxidant treatment and/or silencing of SRs has been shown to reduce atherogenesis. Despite some discrepancies, the indication from cohort studies that there is an association between oxLDL and cardiovascular (CV) events seems to point toward a role for oxLDL in atherosclerotic plaque progress and disruption. Finally, randomized clinical trials using antioxidants have demonstrated benefits only in high-risk patients, suggesting that additional proofs are still needed to better define the involvement of each type of modified LDL in the development of atherosclerosis. © 2016 Elsevier Inc
State-of-the-Art on Basic and Applied Stem Cell Therapy; Stem Cell Research Italy-International Society for Cellular Therapy Europe, Joint Meeting, Montesilvano (PE)-Italy, June 10-12, 2011.
No full textOver 160 stem cell-based therapeutic products are undergoing development for the treatment of several diseases, ranging from cardiac and artery diseases to immune and neurodegenerative pathologies, including diabetes, spinal cord injury. Therefore, stem cell therapy plays a key role for developing new cell-based drugs for the future molecular and regenerative medicine. The second meeting organized by Stem Cell Research Italy (SCR Italy) and by the International Society for Cellular Therapy-Europe (ISCT) in Montesilvano/Citta S. Angelo (Pescara)-Italy, on June 10th-12th, 2011, focused on the state-of-the-art of stem cell therapy and associated novel findings on stem cell research (www.stemcellitaly.org)
Reduced nitric oxide bioavailability in chronic renal failure: a new factor of progression?
No full textNitric oxide (NO) is a gaseous free radical and an important molecular mediator of many physiologic processes in virtually every organ. NO is produced from L-arginine by nitric oxide synthase (NOS). This enzyme is expressed as 3 isoforms, all of which have been isolated from the kidney: endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS). At present it is very difficult to measure authentic nitric oxide in vivo; a way to circumvent the difficulties is to study the effects of NOS stimulation and subsequent nitric oxide release directly by measurement of the resulting changes in vascular tone. In the kidney and vasculature, NO plays fundamental roles in the control of systemic and intrarenal hemodynamics, the tubuloglomerular feedback response, pressure natriuresis, release of sympathetic neurotransmitters and renin, and tubular solute and water transport. Chronic renal failure (CRF) is a state of NO deficiency secondary to decreased NO production and/or increased bioinactivation of NO by reactive oxygen species. The purpose of this review is to examine the functions of NO in the kidney, and to discuss the effects of NO deficiency in the progression of chronic kidney disease
Involvement of the TRAIL-TRAIL/Receptors (TRAIL-R) system in the model of gestational diabetes (GD)
No full textInsulin enhances vascular adhesion molecule (VCAM-1) expression in human cultured endothelial cells through a pro-atherogenic p38MAP-kinase mediated pathway.
No full textAims/hypothesis. Although hyperinsulinaemia in Type 2 diabetes in states of insulin resistance is a risk factor for atherosclerotic vascular disease, underlying mechanisms are poorly understood. We tested the hypothesis that insulin increases monocyte-endothelial interactions, which are implicated in atherosclerosis.
Methods. We treated human umbilical vein endothelial cells with insulin (10(-10) to 10(-7) mol/l) for 0 to 24 h. To dissect potentially implicated signal transduction pathways, we treated endothelial cells with known pharmacological inhibitors of two distinct insulin signalling pathways: the phosphatidylinositol-3'-kinase (PI3'-kinase) inhibitor wortmannin (3x10(-8) to 10(-6) mol/l), involved in insulin-induced endothelial nitric oxide synthase stimulation, and the p38 mitogen-activated protein (p38MAP) kinase inhibitor SB-203580 (10(-7) to 2x10(-6) mol/l). We measured adhesion molecule expression by cell surface enzyme immunoassays and U937 monocytoid cell adhesion in rotational adhesion assays.
Results. At pathophysiological concentrations (10(-9) to 10(-7) mol/l), insulin concentration-dependently induced vascular cell adhesion molecule (VCAM)-1 (average increase: 1.8-fold) peaking at 16 h. By contrast, the expression of intercellular adhesion molecule-1 and E-selectin were unchanged. The effect on VCAM-1 was paralleled by increased U937 cell adhesion. In the absence of cytotoxicity, wortmannin significantly potentiated the effect of insulin alone on VCAM-1 surface expression and monocytoid cell adhesion, whereas SB-203580 (10(-6) mol/l) completely abolished such effects.
Conclusions/interpretation. These observations indicate that insulin promotes VCAM-1 expression in endothelial cells through a p38MAP-kinase pathway, amplified by the PI3'-kinase blockage. This could contribute to explaining the increased atherosclerosis occurring in subjects with hyperinsulinaemia, or in states of insulin resistance, which feature a defective PI3'-kinase pathway
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