Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sickle cell disease (SCD), the first 'molecular disease' to be identified, has been well characterized as a single amino acid molecular disorder of hemoglobin leading to its pathological polymerization, with resulting red cell rigidity that causes poor microvascular blood flow, with consequent tissue ischemia and infarction. Thus, the manifestations of SCD chronic renal disease have long been considered clinical manifestations of an obstructive vasculopathy of the arterial and capillary microcirculation. Recently, accumulating evidence have indicated that blood vessel functions are affected by SCD, involving abnormal vascular tone and activated endothelium. These abnormalities are particularly prominent in the kidney where specific biochemical conditions in the medulla and papilla favor change in endothelial phenotype and in tubular phenotype that, in turn, may promote dysfunction and destruction of this organ through active endothelin (ET)-1 production and signals. High ET-1 urinary output in SCD subjects at steady state may reflect increased tubular activation of ET-1 production acting on the collecting duct thereby favoring the constant hyposthenuria. Chronically, augmented ET-1 concentrations in the SCD kidney would further aggravate ischemia and sickling through actions on vasa recta and red blood cells. The kidneys suffer multiple ischemic hits during SCD as consequences of vasos-occlusive crisis (VOC). Blockade of ET receptors unraveled the major vasoconstrictive role of ET-1 in the pathophysiology of VOC, stressing the pivotal role of abnormal endothelial phenotype in this hemoglobinopathy and opening potential new therapeutic options. At last, indirect evidence suggest that ET-1 may be involved in the progression of chronic glomerulosclerosis affecting a number of patients. In fact, sickle cell nephropathy is an emerging severe disease that requires pathophysiological studies and development of specific therapies.
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PMID:Endothelin in renal injury due to sickle cell disease. 2189 99