Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Common therapeutic strategies for peripheral arterial disease often fail to re-establish sufficient blood flow within legs and feet of patients for avoiding critical limb ischemia, what is characterized by a substantial risk for amputation. The neuropeptide secretoneurin induces angiogenesis in models of limb and myocardial ischemia and might be a promising tool in the treatment of patients without the option of revascularization therapy for severe ischemia. Within this manuscript, the biologically active part of secretoneurin was identified, modified by induction of a cysteine residue to gain higher stability against enzymatic degradation and further packed into S-protected thiolated chitosan nanoparticles, which enable intra-muscular application of secretoneurin. Secretoneurin nanoparticles restored blood flow in a mouse hind limb ischemia model within one week, whereas control particles did not. In vitro testing also revealed the angiogenic, antiapoptotic and proliferative effects of the new secretoneurin derivate, as tested in primary human umbilical vein endothelial cells. With the work from this study we provide a new promising tool for treatment of peripheral arterial disease.
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PMID:Nanoparticular delivery system for a secretoneurin derivative induces angiogenesis in a hind limb ischemia model. 2816 85

The neuropeptide secretoneurin (SN) plays protective roles in myocardial ischemia. In the present study, the effect of SN in cardiac hypertrophy was investigated. We observed that, in isoproterenol (ISO) treatment induced cardiac or cardiomyocytes hypertrophy, a marked increase in the expression of endogenous SN in mouse plasma, myocardium and primary-cultured cardiomyocytes occurs. In hypertrophic mice, the heart size, heart weight/body weight (HW/BW) ratio, cardiomyocyte size, and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression were significantly higher than those in controls but were effectively suppressed by SN gene therapy. Similarly, the protective effects of SN were also observed in cultured cardiomyocytes following ISO treatment. SN significantly increased the activity of catalase and superoxide dismutase (SOD) in parallel with the decrease in reactive oxygen species levels in cardiomyocytes. We observed that SN evoked the activation of all of the AMPK, P38/MAPK and ERK/MAPK pathways in cardiomyocytes, but pretreatment with only AMPK inhibitor (compound C) and ERK1/2/MAPK inhibitor (PD98059) counteracted the protective effects of SN against cardiomyocyte hypertrophy and the suppressive effects of SN on oxidant stress in cardiomyocytes. These results indicated that endogenous SN is induced in hypertrophic cardiomyocytes, and may play a protective role in the pathogenesis of cardiac hypertrophy. These results suggest that exogenous SN supplementation protects the cardiac hypertrophy induced by ISO treatment through the activation of AMPK and ERK/MAPK pathways, thus upregulating antioxidants and suppressing oxidative stress.
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PMID:Secretoneurin suppresses cardiac hypertrophy through suppression of oxidant stress. 2933 95

The pathogenesis of diabetic neuropathy remains enigmatic. Damage to the vasa nervorum may be responsible for this disorder. Recently, we showed that secretoneurin (SN) induces angiogenesis in hindlimb and myocardial ischemia. Moreover, beneficial effects were observed in wound healing. We therefore hypothesized that SN therapy may ameliorate diabetic neuropathy. We used db/db mice as animal model for neuropathy. Gene therapy was accomplished by intramuscular injection of SN plasmid along the sciatic nerve. Sciatic nerve motor and sensory conduction velocities were then measured for 9 wk. Nerve conduction velocities showed normal values in heterozygous mice for the observational period, but were severely reduced in homozygous mice in which velocities were significantly improved by SN, but not by control plasmid gene therapy. The reaction time in the tail-flick test improved significantly in SN-treated animals. The induction of growth of vasa nervorum seems to be part of the underlying mechanism. In addition, SN positively affected Schwann cell function in vitro and induced activation of important signaling pathways. Our observations suggest that SN exerts beneficial effects on nerve function in vivo and on Schwann cells in vitro. It therefore may be a promising treatment option for diabetic neuropathy.-Theurl, M., Lener, D., Albrecht-Schgoer, K., Beer, A., Schgoer, W., Liu, Y., Stanzl, U., Fischer-Colbrie, R., Kirchmair, R. Gene therapy with the angiogenic neuropeptide secretoneurin ameliorates experimental diabetic neuropathy.
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PMID:Gene therapy with the angiogenic neuropeptide secretoneurin ameliorates experimental diabetic neuropathy. 2991 55