Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intact cholesterol homeostasis helps to maintain hematopoietic stem and multipotential progenitor cell (HSPC) quiescence. Mice with defects in cholesterol efflux pathways due to deficiencies of the ATP binding cassette transporters ABCA1 and ABCG1 displayed a dramatic increase in HSPC mobilization and extramedullary hematopoiesis. Increased extramedullary hematopoiesis was associated with elevated serum levels of G-CSF due to generation of IL-23 by splenic macrophages and dendritic cells. This favored hematopoietic lineage decisions toward granulocytes rather than macrophages in the bone marrow leading to impaired support for osteoblasts and decreased Cxcl12/SDF-1 production by mesenchymal progenitors. Greater HSPC mobilization and extramedullary hematopoiesis were reversed by raising HDL levels in Abca1(-/-)Abcg1(-/-) and Apoe(-/-) mice or in a mouse model of myeloproliferative neoplasm mediated by Flt3-ITD mutation. Our data identify a role of cholesterol efflux pathways in the control of HSPC mobilization. This may translate into therapeutic strategies for atherosclerosis and hematologic malignancies.
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PMID:Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol efflux pathways. 2286 39

Malignant and cardiovascular disorders are the top causes of mortality worldwide. This article reviews the main literature data and mechanisms linking hematologic malignancies and arterial stiffness, focusing on recent experimental and clinical results. Several links were found in hematologic malignancies between complete blood count and arterial stiffness. Chemotherapy, especially anthracyclines, cyclophosphamide and tyrosine kinase inhibitors, as well as radiotherapy and hematopoietic stem cell transplantation are the main known causes of arterial stiffness increase in hematologic malignancies. The mechanisms of arterial stiffness elevation in hematologic malignancies include an increased oxidative stress, impaired vascular wall homeostasis, endothelial dysfunction and apoptosis of endothelial cells, overexpression of inflammatory cytokines, accelerated atherosclerosis, increased blood viscosity and unstable platelet aggregates. Guidelines regarding cardiovascular health screening and cardiovascular risk scores are necessary for hematologic cancer survivors in order to improve prognosis and quality of life of the patients.
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PMID:Arterial stiffness in hematologic malignancies. 2842 54

Proteasome inhibitors such as bortezomib and carfilzomib have been used effectively to treat patients who have certain hematologic malignancies. Proteasome activity is elevated in the heart, and potent inhibition results in accumulation of misfolded intracellular protein aggregates and apoptosis. Heart failure, conduction disturbances, and premature atherosclerosis have been associated with bortezomib therapy. We describe the case of a 49-year-old man who was taking bortezomib for graft-versus-host disease, when he developed cardiac tamponade and needed emergency pericardiocentesis. At that time, there was no evidence of graft-versus-host disease. To our knowledge, this is the first time that a pericardial effusion without underlying cardiac dysfunction has been reported in relation to bortezomib therapy. The diagnosis of pericardial effusion during bortezomib therapy, the absence of other causative agents-including graft-versus-host disease-and no recurrence of pericardial effusion after discontinuing bortezomib therapy suggest that bortezomib caused our patient's tamponade.
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PMID:Bortezomib-Induced Cardiac Tamponade in a 49-Year-Old Man. 3037 42

In hematopoiesis, mature blood cells, granulocytes, erythrocytes, and megakaryocytes originate from hematopoietic stem cells. With age, changes in hematopoiesis may have clinical consequences: defective immune responses, cytopenias (most commonly anemia and lymphopenia), hematological malignancy, and effects mediated by hematopoietic cells in other organs. Clonal hematopoiesis is commonly seen with aging and has been associated with both blood concerns and atherosclerosis, but further study is required to determine a causative link.
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PMID:Aging and Hematopoiesis. 3123 Jul 30