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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Humoral regulation of somatic and hematopoietic cell growth has been intensely investigated during the past decade. Growth hormone is unique because it regulates the size of the person within the constraints of the genetic program. The somatomedins and insulin growth factors are low molecular weight polypeptides believed to mediate some functions of growth hormone. Epithelial growth factor and nerve growth factor are well-characterized polypeptides that influence the growth and differentiation of epithelial and neural tissues and interact with specific cell surface receptors. The hematopoietins are a family of polypeptide hormones that specifically regulate the proliferation and differentiation of stem cells giving rise to erythrocytes, granulocytes, monocytes, megakaryocytes, and B and T lymphocytes. Platelet-derived growth factor modulates the proliferation of fibroblasts in vitro and may have a role in the development of atherosclerosis and myelofibrosis. New knowledge on the biochemistry and physiology of growth factors will probably have a substantial impact on our understanding of human diseases involving abnormal cell growth.
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PMID:Growth factors. 699 74

Most previous researches on neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) have focused on the nervous system, because their receptors are widely distributed in neuronal tissues. Recently, however, the participation of neurotrophins in inflammation and atherosclerosis has been proposed. Therefore, the gene expression of neurotrophins is now an urgent issue is to be investigated in nonneuronal tissues. Here, we evaluated the gene expression of neurotrophins and their receptors in rat cultured vascular smooth muscle cells (VSMCs) by the reverse transcriptase-polymerase chain reaction method. The transcripts of NGF, NT-3, and TrkC (high-affinity receptor for NT-3), and two BDNF alternative spliced transcript variants with exons 3 and 4 were clearly detected in VSMCs cultured under conventional culture conditions. The upregulation of mRNA levels for NGF, two BDNF variants with exons 1 and 2, low-affinity neurotrophin receptor, and high-affinity receptors, TrkA (for NGF) and TrkB (for BDNF), was observed in response to the treatment with serum and phorbol-ester following the serum-starvation. In contrast, the expression of NT-3 and TrkC genes was downregulated under these conditions. Co-expression of these factors and their receptors and the characteristic regulation of their gene transcriptions suggest that these factors play crucial roles in the function of VSMCs through an autocrine mechanism.
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PMID:Gene expression of neurotrophins and their receptors in cultured rat vascular smooth muscle cells. 953 23

In addition to their stimulatory action on neuronal differentiation and survival, the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) improve glucose and lipid metabolism and control energy balance and feeding behavior. These latter activities are referred to here as the metabotrophic potential of neurotrophins. We recently reported that circulating NGF and BDNF levels are reduced in the metabolic syndrome and in acute coronary syndromes, and that the tissue content of NGF is reduced in atherosclerotic coronary arteries. Thus we hypothesize that a metabotrophic deficit due to reduction of neurotrophin availability may be implicated in the pathogenesis of obesity and related metabolic diseases, such as metabolic syndrome, type 2 diabetes, and atherosclerosis. The metabotrophic deficit hypothesis also considers metabolism-related beneficial effects exerted by other neurotrophic factors, particularly ciliary neurotrophic factor, leukemia inhibitory factor, and bone morphogenetic proteins.
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PMID:Metabotrophic potential of neurotrophins:implication in obesity and related diseases? 1452 35

The development of atherosclerotic cardiovascular disease is a common comorbidity in patients with the metabolic syndrome, a concurrence of cardiovascular risk factors in one individual. While multiple growth factors and adipokines are identified in atherosclerotic lesions, as well as neurotrophins implicated in both cardiac ischemia and lipid and glucose metabolism, the potential role of neurotrophins in human coronary atherosclerosis and in the metabolic syndrome still remains to be elucidated. Here we describe and discuss our results that represent a novel attempt to study the cardiovascular and metabolic biology of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and mast cells (MC). The local amount of NGF, the immunolocalization of p75 neurotrophin receptor (p75NTR) and the number of MC were correlatively examined in coronary vascular wall and in the surrounding subepicardial adipose tissue, obtained from autopsy cases in humans with advanced coronary atherosclerosis. We also analyzed the plasma levels of NGF, BDNF and leptin and the number of MC in biopsies from abdominal subcutaneous adipose tissue in patients with a severe form of the metabolic syndrome. The results demonstrate that NGF levels are decreased in atherosclerotic coronary vascular tissue but increased in the subepicardial adipose tissue, whereas both tissues express a greater number of MC and a stronger p75NTR immunoreactivity, compared to controls. Metabolic syndrome patients display a significant hyponeurotrophinemia and an increased number of adipose MC; the later correlates with elevated plasma leptin levels. In effect, we provide the first evidence for (i) an altered presence of NGF, p75NTR and MC in both coronary vascular and subepicardial adipose tissue in human coronary atherosclerosis, and (ii) a significant decrease in plasma NGF and BDNF levels and an elevated amount of plasma leptin and adipose MC in metabolic syndrome patients. Together our findings suggest that neuroimmune mediators such as NGF, BDNF, leptin and MC may be involved in the development of cardiovascular disease and related disorders.
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PMID:Neurotrophin presence in human coronary atherosclerosis and metabolic syndrome: a role for NGF and BDNF in cardiovascular disease? 1469 70

CD40, a member of the nerve growth factor/tumor necrosis factor receptor superfamily, and its ligand, CD154, play essential roles in cell immune responses. The results of many studies have indicated that CD40-CD154 interaction can upregulate costimulatory molecules, activate antigen-presenting cells (APCs), influence T-cell priming and T-cell-mediated effector functions as well as participate in the pathogenic processing of chronic inflammatory diseases, such as autoimmune diabetes, graft rejection, atherosclerosis, and cancer. Ligation of CD40 on cancer cells was also found to produce a direct growth-inhibitory effect through cell cycle blockage and/or apoptosis with no overt side effects on normal cells and treatment with CD154 can heighten tumor rejection immune response as well. However, systemic treatment with CD154 has some potential risks. Therefore, searching for efficient and safe strategies of CD154-based cancer therapy has been a hot topic in human cancer research. This review focuses on the latest discovered functions of CD40-CD154 interaction in cell immune responses and on the new findings of CD154-based human cancer therapy.
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PMID:The role of CD40-CD154 interaction in cell immunoregulation. 1515 77

The field of neurotrophins, particularly, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), has witnessed a number of breakthroughs in recent years. There is evidence now that NGF and BDNF mediate multiple biological phenomena, ranging from the Rita Levi Montalcini's neurotrophic through immunotrophic to epitheliotrophic and nociceptive effects. In 2003 we, for the first time, enriched the "NGFome" with one more expression presented in our concept of NGF metabotrophicity, also that of BDNF. This envisages that these two factors may operate as metabotrophins, that is, involved in the maintenance of cardiometabolic homeostasis (glucose and lipid metabolism as well as energy balance, cardioprotection, and wound healing). Recent results also demonstrated that the circulating and/or tissue levels of NGF and BDNF are altered in cardiometabolic diseases (atherosclerosis, obesity, type 2 diabetes, metabolic syndrome, and type 3 diabetes). Altogether, a hypothesis of metabotrophic deficit due to the reduction of NGF/BDNF availability and/or utilization was raised, and implicated in the pathogenesis of cardiometabolic diseases. This may cultivate a novel pathogenic and therapeutic thinking for these diseases.
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PMID:The metabotrophic NGF and BDNF: an emerging concept. 2170 97

Calcitonin gene-related peptide (CGRP) is a major neurotransmitter and CGRP-containing primary sensory neurons play an important role in nociception and potent vasodilation. CGRP-containing nerves in mesenteric arteries are decreased in pathological animal models (hypertension, diabetes, and atherosclerosis). In apolipoprotein E–knockout mice, which have atherosclerosis and peripheral sensory nerve defects, nerve growth factor (NGF)-mediated CGRP nerve facilitation was down-regulated, which may have been caused by the impairment of the Akt–NO–cGMP pathway. In addition, NGF-mediated CGRP neurite outgrowth was decreased in fructose-induced insulin-resistant rats. We recently discovered that renin–angiotensin inhibitors improved CGRP innervation in spontaneously hypertensive rats, indicating that rescuing CGRP nerve innervation might improve pathophysiological conditions. To find a novel reagent that facilitates CGRP nerves, a new model, phenol-injured perivascular nerve model rats, was established. Adrenomedullin, hepatocyte growth factor, and angiotensin II type 2 receptor activation induced CGRP nerve distribution in phenol-injured rats. Furthermore, in insulin-resistant model rats, the down-regulation of CGRP nerves was likely due to the depression of phosphoinositide 3-kinase (PI3K)-dependent Akt activation. Administration of candesartan improves CGRPergic function via the PI3K–Akt pathway in insulin-resistant rats. Thus, clarification of the mechanisms of CGRP nerve defects may constitute future therapeutic targets.
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PMID:The mechanism of calcitonin gene-related peptide-containing nerve innervation. 2267 32

Important advances in our understanding of the relationships between adipose tissue derived peptides, namely adipokines, and their effects on cardiovascular functions have been achieved in recent years. Growing knowledge of adipokine biology is revealing the complexity of these proteins. Adipose tissue releases some other proteins called neurotrophins that are mainly active in central and peripheral nervous system. However, secretion and activity of these hormones are not only limited to neuronal cells and tissues, but they also take part in adipose tissue development, energy metabolism, glucose utilization, insulin sensitivity, inflammation, lipoprotein synthesis, and atherosclerosis. In this review, we describe the most recent advances in the functions of brain derived nerve growth factor (BDNF), a major type of neurotrophins, focusing primarily on cardiovascular and metabolic diseases.
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PMID:Brain derived neurotrophic factor (BDNF) in cardiometabolic physiology and diseases. 2298 97

The first cell growth factor, nerve growth factor (NGF), was discovered by Rita Levi-Montalcini (RLM) in the early 1950s. Originally identified as neurite outgrowth-stimulating factor, later studies revealed that non-neuronal cells, including immune cells, endothelial cells, cardiomyocytes, pancreatic beta cells, prostate epithelial and adipose tissue cells, were also targets for and/or sources of NGF. Nerve growth factor is well recognised as mediating multiple biological phenomena, ranging from the neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects. Consequently, NGF and other members of the neurotrophin family are implicated in the pathogenesis of a large spectrum of neuronal and non-neuronal diseases, ranging from Alzheimer's and other neurodegenerative diseases to atherosclerosis and cardiometabolic disorders. Recent studies have demonstrated the therapeutic potentials of NGF in these conditions, including ocular and cutaneous diseases. NGF TrkA receptor antagonists emerged as novel drugs for pain, prostate and breast cancer, melanoma and urinary bladder syndromes. Here, we briefly describe the 'unpredictable' ideogenesis of the discovery of NGF, a eureka in the neuroscience.
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PMID:Homage to Rita Levi-Montalcini, the queen of modern neuroscience. 2352 Jan 36

Metabolic syndrome (MetS) is a complex and heterogeneous disease characterized by central obesity, impaired glucose metabolism, dyslipidemia, arterial hypertension, insulin resistance and high-sensitivity C-reactive protein. In 2006, a neurotrophic hypothesis of the etiopathogenesis of MetS was launched. This hypothesis considered the neurotrophins a key factor in MetS development. Chronic inflammatory and/or psychoemotional distress provoke a series of neuroimmunoendocrine interactions such as increased tissue and plasma levels of proinflammatory cytokines and neurotrophins, vegetodystonia, disbalance of neurotransmitters, hormones and immunity markers, activation of the hypothalamo-pituitary-adrenal axis, insulin resistance, and atherosclerosis. An early and a late clinical stage in the course of MetS are defined. Meanwhile, evidence of supporting results from the world literature accumulates. This enables the transformation of the definition of the neurotrophic hypothesis into a neurotrophic theory of MetS. The important role of two neurotrophic factors, i.e. the nerve growth factor and brain-derived neurotrophic factor as well as of the proinflammatory cytokines, neurotransmitters, adipokines and, especially, of leptin for the development of MetS, obesity and type 2 diabetes mellitus is illustrated. There are reliable scientific arguments that the metabotrophic deficit due to reduced neurotrophins could be implicated in the pathogenesis of MetS, type 2 diabetes mellitus, and atherosclerosis as well. A special attention is paid to the activity of the hypothalamo-pituitary-adrenal axis after stress. The application of the neurotrophic theory of MetS could contribute to the etiological diagnosis and individualized management of MetS by eliminating the chronic distress, hyponeurotrophinemia and consequent pathology. It helps estimating the risk, defining the prognosis and implementing the effective prevention of this socially significant disease as evidenced by the dramatic recent growth of the world publication output on this interdisciplinary topic.
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PMID:Metabolic syndrome--from the neurotrophic hypothesis to a theory. 2389 30


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