Vladimir Nikolaev Martinov

• Hjorth, Marit; Norheim, Frode; Meen, Astri Jeanette; Pourteymour, Shirin; Lee, Sindre & Holen, Torgeir [Vis alle 13 forfattere av denne artikkelen] (2015). The effect of acute and long-term physical activity on extracelluar Matrix and serglycin in huuman skeletal muscle. Physiological Reports. ISSN 2051-817X. 3:e12473(8), s. 1–19. doi: 10.14814/phy2.12473.
• Martinov, Vladimir Nikolkaev; Dehnes, Yvette; Holmseth, Silvia; Shimamoto, Keiko; Danbolt, Niels Christian & Valen, Guro (2014). A novel glutamate transport blocker, LL-TBOA, attenuates ischemic injury in the isolated, perfused rat heart despite low transporter levels. European Journal of Cardio-Thoracic Surgery. ISSN 1010-7940. 45(4), s. 710–716. doi: 10.1093/ejcts/ezt487.
• Gravning, Jørgen A.; Ørn, Stein; Kaasbøll, Ole Jørgen; Martinov, Vladimir Nikolkaev; Manhenke, Cord A & Dickstein, Kenneth [Vis alle 9 forfattere av denne artikkelen] (2012). Myocardial Connective Tissue Growth Factor (CCN2/CTGF) Attenuates Left Ventricular Remodeling after Myocardial Infarction. PLOS ONE. ISSN 1932-6203. 7(12). doi: 10.1371/journal.pone.0052120. Vis sammendrag

  Aims: Myocardial CCN2/CTGF is induced in heart failure of various etiologies. However, its role in the pathophysiology of left ventricular (LV) remodeling after myocardial infarction (MI) remains unresolved. The current study explores the role of CTGF in infarct healing and LV remodeling in an animal model and in patients admitted for acute ST-elevation MI. Methods and Results: Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) and non-transgenic littermate controls (NLC) were subjected to permanent ligation of the left anterior descending coronary artery. Despite similar infarct size (area of infarction relative to area at risk) 24 hours after ligation of the coronary artery in Tg-CTGF and NLC mice, Tg-CTGF mice disclosed smaller area of scar tissue, smaller increase of cardiac hypertrophy, and less LV dilatation and deterioration of LV function 4 weeks after MI. Tg-CTGF mice also revealed substantially reduced mortality after MI. Remote/peri-infarct tissue of Tg-CTGF mice contained reduced numbers of leucocytes, macrophages, and cells undergoing apoptosis as compared with NLC mice. In a cohort of patients with acute ST-elevation MI (n = 42) admitted to hospital for percutaneous coronary intervention (PCI) serum-CTGF levels (s-CTGF) were monitored and related to infarct size and LV function assessed by cardiac MRI. Increase in s-CTGF levels after MI was associated with reduced infarct size and improved LV ejection fraction one year after MI, as well as attenuated levels of CRP and GDF-15. Conclusion: Increased myocardial CTGF activities after MI are associated with attenuation of LV remodeling and improved LV function mediated by attenuation of inflammatory responses and inhibition of apoptosis.

• Czibik, Gabor Tamas; Gravning, Jørgen A.; Martinov, Vladimir Nikolkaev; Ishaq, Bushra; Knudsen, Eirunn & Attramadal, Håvard [Vis alle 7 forfattere av denne artikkelen] (2011). Gene therapy with hypoxia-inducible factor 1 alpha in skeletal muscle is cardioprotective in vivo. Life Sciences. ISSN 0024-3205. 88(11-12), s. 543–550. doi: 10.1016/j.lfs.2011.01.006. Vis sammendrag

  Aims: Gene therapy of a peripheral organ to protect the heart is clinically attractive. The transcription factor hypoxia-inducible factor 1 alpha (HIF-1 alpha) transactivates cardioprotective genes. We investigated if remote delivery of DNA encoding for HIF-1 alpha is protective against myocardial ischemia-reperfusion injury in vivo. Main methods: DNA encoding for human HIF-1 alpha was delivered to quadriceps muscles of mice. One week later myocardial infarction was induced and four weeks later its size was measured. Echocardiography and in vivo pressure-volume analysis was performed. Coronary vascularization was evaluated through plastic casting. HL-1 cells, transfected with either HIF-1 alpha or HMOX-1 or administered bilirubin or the carbon monoxide (CO) donor CORM-2, were subjected to lipopolysacharide (LPS)-induced cell death to compare the efficacy of treatments. Key findings: After four weeks of reperfusion post infarction, animals pretreated with HIF-1 alpha showed reduced infarct size and left ventricular remodeling (p<0.05, respectively). Fractional shortening was preserved in mice pretreated with HIF-1 alpha (p<0.05). Invasive hemodynamic parameters indicated preserved left ventricular function after HIF-1 alpha (p<0.05), which also induced coronary vascularization (p<0.05). HIF-1 alpha downstream target heme oxygenase 1 (HMOX-1) was upregulated in skeletal muscle, while serum bilirubin was increased. Transfection of HL-1 cells with HIF-1 alpha or HMOX-1 and administration of bilirubin or CORM-2 comparably salvaged cells from lipopolysacharide (LPS)-induced cell death (all p<0.05). Significance: HIF-1 alpha gene delivery to skeletal muscle preceding myocardial ischemia reduced infarct size and postischemic remodeling accompanied by an improved cardiac function and vascularization. Similar to HIF-1 alpha, HMOX-1, bilirubin and CO were protective against LPS-induced injury. This observation may have clinical potential. (C) 2011 Elsevier Inc. All rights reserved.

• Ahmed, Muhammad Shakil; Gravning, Jørgen A.; Martinov, Vladimir Nikolkaev; von Lueder, Thomas Gero; Edvardsen, Thor & Czibik, Gabor Tamas [Vis alle 11 forfattere av denne artikkelen] (2011). Mechanisms of novel cardioprotective functions of CCN2/CTGF in myocardial ischemia-reperfusion injury. American Journal of Physiology. Heart and Circulatory Physiology. ISSN 0363-6135. 300(4), s. H1291–H1302. doi: 10.1152/ajpheart.00604.2010.
• Czibik, Gabor Tamas; Sagave, Julia Fritzi; Martinov, Vladimir Nikolkaev; Ishaq, Bushra; Sohl, M & Sefland, Iren [Vis alle 10 forfattere av denne artikkelen] (2009). Cardioprotection by hypoxia-inducible factor 1 alpha transfection in skeletal muscle is dependent on haem oxygenase activity in mice. Cardiovascular Research (CVR). ISSN 0008-6363. 82(1), s. 107–114. doi: 10.1093/cvr/cvp035.
• Czibik, Gabor Tamas; Martinov, Vladimir Nikolkaev; Ruusalepp, Arno; Sagave, Julia Fritzi; Skare, Øivind & Valen, Guro (2009). In vivo Remote Delivery of DNA Encoding for Hypoxia-Inducible Factor 1 Alpha Reduces Myocardial Infarct Size. Clinical and Translational Science (CTS). ISSN 1752-8054. 2(1), s. 33–40. doi: 10.1111/j.1752-8062.2008.00077.x.
• Martinov, Vladimir Nikolkaev; Rizvi, Syed Mohammad H.; Sagave, Julia Fritzi; Bergersen, Linda Hildegard & Valen, Guro (2009). Increased expression of monocarboxylate transporter 1 after acute ischemia of isolated perfused mouse hearts. Life Sciences. ISSN 0024-3205. 85, s. 379–385.
• Martinov, Vladimir Nikolaev & Njå, Arild (2005). A microcapsule technique for long-term conduction block of the sciatic nerve by tetrodotoxin. Journal of Neuroscience Methods. ISSN 0165-0270. 141(2), s. 199–205. Vis sammendrag

  Tetrodotoxin (TTX) is a selective blocker of voltage-gated Na(+) channels that is used to block action potentials in vitro and in vivo. Maintaining a sufficiently high local concentration of TTX in vivo to block conduction in a peripheral nerve is technically demanding and carries a risk of systemic toxicity. We report that slow diffusion of TTX out of a microcapsule (glass capillary) inserted beneath the epineurium of the sciatic nerve, with a loose cuff around the nerve, combines high blocking efficacy with low systemic toxicity in rats and mice. The local anaesthesia and motor paralysis was stable for at least 4-6 weeks. The conduction block was reversible and did not cause any obvious nerve injury. Low cost and simple surgical implementation make this new system an interesting alternative to existing long-term drug delivery methods.

• Reid, Brian; Martinov, Vladimir Nikolaev; Njå, Arild; Lømo, Terje & Bewick, Guy S. (2003). Activity-dependent plasticity of transmitter release from nerve terminals in rat fast and slow muscles. Journal of Neuroscience. ISSN 0270-6474. 23(28), s. 9340–9348. Vis sammendrag

  Neuromuscular junctions (NMJs) on fast and slow muscle fibers display different transmitter release characteristics that appear well adapted to the different patterns of nerve impulses that they transmit in vivo. Here, we ask whether the release properties of such NMJs, termed fast and slow, can be transformed by chronic nerve stimulation. In young adult rats, nerve impulse conduction in the sciatic nerve was blocked by TTX, and the nerve to the fast extensor digitorum longus (EDL) or the slow soleus (SOL) muscle stimulated directly below the block with slow (20 Hz for 10 sec every 30 sec) or fast (150 Hz for 1 sec every 60 sec) stimulus patterns, respectively. After 3-4 weeks, originally fast EDL-NMJs and slow SOL-NMJs had become almost fully transformed to slow and fast NMJs, respectively, with respect to maintenance of transmitter release during tonic 20 Hz stimulation in vitro and ratio of quantal content to vesicle pool size. TTX block alone had no such transforming effect. Vesicle recycle time was unaffected by the stimulation, whereas initial quantal content and vesicle pool size were reduced (by 49% and 57% in EDL and 33% and 67% in SOL). Muscle fiber diameter also declined (by 49% in EDL and 33% in SOL vs 46% in unstimulated SOL; unstimulated EDL was not examined). We conclude that fast and slow NMJs display marked plasticity by being able to adapt important release characteristics to the impulse patterns imposed on them.

• Martinov, Vladimir Nikolaev; Sefland, Iren; Walaas, Sven Ivar; Lømo, Terje; Njå, Arild & Hoover, Frank (2002). Targeting functional subtypes of spinal motoneurons and skeletal muscle fibers in vivo by intramuscular injection of adenoviral and adeno-associated viral vectors. Anatomy and Embryology. ISSN 0340-2061. 205, s. 215–221. Vis sammendrag

  We report that functional subtypes of spinal motoneurons and skeletal muscle fibers can be selectively transduced using replication-defective adenoviral (ADV) or adeno-associated (AAV) viral vectors. After intramuscular injection in adult rodents, ADV vectors transduced both fast-twitch and slow-twitch skeletal muscle fibers. Intramuscular injection of ADV vectors also caused transduction of spinal motoneurons and dorsal root ganglion cells. However, only neurons innervating the injected muscle were transduced, as shown by co-injection of a retrograde axonal tracer. In adult male rats it is therefore possible to transduce fast or slow spinal motoneurons and muscle fibers selectively since in these animals, the extensor digitorum longus and soleus muscles contain almost exclusively fast or slow motor units, respectively. In rats, AAV vectors transduced muscle fibers in the predominantly fast extensor digitorum longus but not in the predominantly slow soleus muscle. We did not observe any transduction of spinal motoneurons following intramuscular injection of AAV vectors. These results show that physiologically and clinically important subpopulations of cells in the neuromuscular system can be selectively transduced by viral vectors.

• Steyern, Fredrik Vult von; Martinov, Vladimir Nikolaev; Rabben, Inger; Njå, Arild; Laperière, Odile de & Lømo, Terje (1999). The homeodomain transcription factors Islet 1 and HB9 are expressed in adult alpha and gamma motoneurons identified by selective retrograde tracing. European Journal of Neuroscience. ISSN 0953-816X. 11, s. 2093–2102. Vis sammendrag

  To study gene expression in differentiated adult motoneuron subtypes, we used fluorescent dextrans for both anterograde and retrograde axonal tracing in adult rat and mouse. Application of these dyes to the cut distal and proximal ends of small extramuscular nerve branches revealed both the peripheral ramifications and the cell bodies of subsets of motoneurons. We show that the soleus muscle is innervated by two nerve branches, one of which contains gamma motor and sensory axons but no alpha motor axons. By retrograde tracing of this branch, we selectively labelled gamma motoneurons. In adult rat, the nerves innervating the soleus and extensor digitorum longus muscles contain almost exclusively axons innervating slow (type I) and fast (type 2) muscle fibres, respectively. We selectively labelled slow and fast type motoneurons by retrograde tracing of these nerves. With immunocytochemistry we show that adult motoneurons express several homeodomain genes that are associated with motoneuron differentiation during early embryonic development. Combining selective retrograde labelling with immunocytochemistry we compared the expression patterns in alpha and gamma motoneurons. The homeodomain transcription factors Islet 1 and HB9 were expressed in slow and fast alpha motoneurons and in soleus gamma motoneurons. Motoneurons in each population varied in their intensity of the immunostaining, but no factor or combination of factors was unique to any one population.

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• Gravning, Jørgen A.; Attramadal, Håvard; Martinov, Vladimir Nikolkaev & Ahmed, Muhammad Shakil (2009). CCN2/CTGF, Connective Tissue Growth Factor, Prevents Heart Failure and Improves Survival After Myocardial Infarction. Circulation. ISSN 0009-7322. 120(18), s. S719–S719.
• Sagave, Julia Fritzi; Czibik, Gabor Tamas; Martinov, Vladimir Nikolkaev & Valen, Guro (2008). A possible role for heme oxygenase 1 in myocardial protection afforded by hypoxia inducible factor 1 alpha. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 44. doi: 10.1016/j.yjmcc.2008.02.040.
• Czibik, Gabor Tamas; Gravning, Jørgen Amundsen; Martinov, Vladimir Nikolkaev; Attramadal, Håvard & Valen, Guro (2008). Remote delivery of DNA encoding for hypoxia-inducible factor 1 alpha protects against myocardial remodeling in vivo. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 44, s. 736–737. doi: 10.1016/j.yjmcc.2008.02.062.
• Czibik, Gabor Tamas; Martinov, Vladimir Nikolaev; Ruusalepp, Arno & Valen, Guro (2006). Gene delivery of hypoxia-inducible factor 1 alpha into skeletal muscle reduces myocardial infarct size 8 weeks later; evaluation of protection. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 40, s. 960–960.
• Martinov, Vladimir Nikolaev; Sefland, Iren; Walaas, Sven Ivar; Lømo, Terje; Njå, Arild & Hoover, Frank (2001). Transduction of nerve- and muscle fibers by recombinant viral vectors in vivo. Vis sammendrag

  Replication deficient viral vectors, based on adenovirus (ADV) or adeno-associated virus (AAV) and encoding green fluorescent protein (GFP), were injected into exposed hindlimb muscles of adult mice under chloral hydrate/pentobarbital anaesthesia (soleus or extensor digitorum longus). Tissues were fixed by cardiac perfusion after a few days to several months, sectioned on a cryostat and examined in a fluorescence microscope. The ADV and AAV vectors both transduced skeletal muscle fibers. The ADV vector also transduced motoneurons innervating the injected muscle but not other spinal cord neurons (as shown by co-injection of the fluorescent retrograde tracer tetramethylrhodamine-dextran). In addition, GFP was detected in sensory neurons in the corresponding dorsal root ganglia (L4-L5). These results indicate that ADV vectors can target identified sets of motor and sensory neurons by endocytosis and retrograde axonal transport after injection into a small leg muscle. The AAV vector causes transduction of skeletal muscle fibers, but does not appear to transduce neurons by retrograde axonal transport. These properties make ADV and AAV vectors valuable tools for carrying gene constructs into the adult neuromuscular system in vivo.

• Njå, Arild; Reid, Brian; Martinov, Vladimir Nikolaev; Wærhaug, Ola; Lømo, Terje & Bewick, Guy S. (2001). Fast and slow motor nerve terminals: Interchanging their impulse activity patterns. Vis sammendrag

  Mammalian motor units differ widely with respect to functional properties and patterns of use. Great demands are placed on slow nerve-muscle synapses in order to keep up transmitter release during prolonged periods of activity. By combining optical and electrical correlates of transmitter release, estimates were obtained for key parameters such as vesicle recycling time, total pool of synaptic vesicles and the fraction of this pool that is exocytosed per nerve impulse. In normal rats, slow terminals have a larger store of synaptic vesicles and lose a smaller fraction of this pool per nerve impulse. We asked whether such neuronal properties are fixed or plastic when impulse patterns are manipulated experimentally, and report that rundown of quantal content in slow nerve terminals that had been chronically activated with a fast pattern (150Hz for 1s every 60s) for 1 month was virtually similar to that in normal fast terminals. Vesicle recycle times were unchanged. These results demonstrate long-term activity-dependent plasticity of adult motor nerve terminals, and suggest that nerve cells have a substantial capacity to change their mode of operation subsequent to novel patterns of training.

• Steyern, Fredrik Vult von; Martinov, Vladimir Nikolaev; Rabben, Inger; Njå, Arild & Lømo, Terje (1998). Selective tracing of peripheral nerves enables identification of defined subsets of spinal motoneurons in rat and mouse.
• Martinov, Vladimir Nikolaev; Steyern, Fredrik Vult von; Rabben, Inger; Njå, Arild & Lømo, Terje (1997). Anterograde and retrograde staining of subsets of spinal motoneurons with fluorescently labeled dextran.
• Martinov, Vladimir Nikolkaev (2004). Studies of platicity in the neuromuscular system: New approaches. Unipub forlag. ISSN 82-8072-117-7.

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