Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxia-induced responses are frequently encountered during cardiovascular injuries. Hypoxia triggers intracellular reactive oxygen species/nitric oxide (NO) imbalance. Recent studies indicate that NO-mediated S-nitrosylation (S-NO) of cysteine residue is a key posttranslational modification of proteins. We demonstrated that acute hypoxia to endothelial cells (ECs) transiently increased the NO levels via endothelial NO synthase (eNOS) activation. A modified biotin-switch method coupled with Western blot on 2-dimensional electrophoresis (2-DE) demonstrated that at least 11 major proteins have significant increase in S-NO after acute hypoxia. Mass analysis by CapLC/Q-TOF identified those as Ras-GTPase-activating protein, protein disulfide-isomerase, human elongation factor-1-delta, tyrosine 3/tryptophan 5-monooxygenase activating protein, and several cytoskeleton proteins. The S-nitrosylated cysteine residue on tropomyosin (Cys 170) and beta-actin (Cys 285) was further verified with the trypsic peptides analyzed by MASCOT search program. Further understanding of the functional relevance of these S-nitrosylated proteins may provide a molecular basis for treating ischemia-induced vascular disorders.
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PMID:Acute hypoxia enhances proteins' S-nitrosylation in endothelial cells. 1899 11

In peripheral arterial disease (PAD), angiogenesis is a major process involved in repairing the microvasculature in the ischemic lower limb. MicroRNA-210 (miR-210) is a microRNA that is substantially increased in patients with PAD. However, the effects of miR-210 on angiogenesis following PAD remain elusive. In the present study, mice with hindlimb ischemia (HLI) were generated as an animal model of PAD, and miR-210 levels were overexpressed in the ischemic limb. The overexpression of miR-210 using microRNA mimics greatly improved angiogenesis and perfusion recovery; in contrast, the knockdown of miR-210 impaired perfusion recovery 28 days after HLI. Ischemic muscle tissue was harvested 7 days after experimental PAD in order to perform biochemical tests, and miR-210 antagonism resulted in increased malondialdehyde levels. In cultured endothelial cells under simulated ischemia, miR-210 mimic improved endothelial cell viability and enhanced tube formation; and a miR-210 inhibitor decreased cell survival, reduced tube formation and increased reactive oxygen species (ROS) levels. Furthermore, miR-210 antagonism increased the protein disulfide-isomerase levels in cultured endothelial cells. These results demonstrate that ischemia-induced miR-210 elevation is adaptive in PAD, and that miR-210 improves angiogenesis at least partially through decreasing ROS production.
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PMID:MicroRNA-210 improves perfusion recovery following hindlimb ischemia via suppressing reactive oxygen species. 3314 89