Made available in DSpace on 2014-06-11T19:31:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-27Bitstream added on 2014-06-13T19:19:53Z : No. of bitstreams: 1 duarte_dr_dr_botfm.pdf: 365312 bytes, checksum: 5b54817ed6d69d3fe0e8673385f863f0 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O hábito de fumar apresenta importante impacto na saúde da população. A associação entre fumo e doença cardiovascular tem sido amplamente explorada em relação à aterosclerose. Recentemente, evidências clínicas e experimentais sugerem que a exposição ao cigarro pode modular o processo de remodelação ventricular. O objetivo desse estudo foi avaliar o papel do inibidor da enzima conversora da angiotensina no processo de remodelação induzido pela exposição à fumaça do cigarro. Ratos Wistar foram distribuídos em três grupos: 1) grupo controle (C, n=8); 2) grupo exposto à fumaça do cigarro (EFC, n=8); 3) grupo exposto à fumaça do cigarro e recebendo 20 mg/kg/dia de lisinopril (EFC-LIS, n=8). Após dois meses os animais foram submetidos ao estudo funcional, morfométrico, e bioquímico. Para a análise estatística foi utilizado o teste de variância ANOVA complementado por Holm-Sidak, o teste Kruskal-Wallis complementado por Tukey e o teste Mann-Whitney. O nível de significância foi 5%. A pressão sistólica caudal foi menor no grupo EFC-LIS (C = 116 ± 27, EFC = 126 ± 16, EFC-LIS = 89 ± 12 mmHg; p = 0,003) em relação aos grupos C e EFC; o grupo EFC apresentou maior valor do diâmetro sistólico do ventrículo esquerdo, corrigido pelo peso (C = 8,25 ± 2,16, EFC = 11,76 ± 1,20, EFC-LIS = 9,27 ± 2,00 mm/kg; p = 0,003), em comparação aos grupos C e EFC-LIS; o diâmetro diastólico do ventrículo esquerdo ajustado pelo peso foi maior nos grupos EFC e EFC-LIS... / The habit of smoking has important impact on population health. The association between tobacco and cardiovascular disease has been widely explored in relation to atherosclerosis. Recently, clinical and experimental evidences suggest that the exposure to tobacco smoke can modulate the process of ventricular remodeling. The objective of that study was to evaluate the role of the angiotensin-converting enzyme inhibitor on cardiac remodeling induced by tobacco smoke exposure. Wistar rats were allocated in three groups: 1) group control (C, n=8); 2) group exposed to tobacco smoke (EFC, n=8); 3) group exposed to tobacco smoke and treated with lisinopril 20mg/kg/day (EFC-LIS, n=8). After two months the animals were submitted to the functional study, morphometric, and biochemical. For the statistical analysis was used the ANOVA test of variance complemented by Holm-Sidak, the test Kruskal-Wallis complemented by Tukey and the test the Mann-Whitney. The significance level was 5%. Results: the caudal systolic pressure was smaller in the group EFC-LIS (C = 116 ± 27, EFC = 126 ± 16, EFC-LIS = 89 ± 12 mmHg; p = 0,003) in relation to the groups C and EFC; the group EFC presented higher value of the systolic diameter of the left ventricle, corrected by body weight (BW) (C = 8,25 ± 2,16, EFC = 11,76 ± 1,20, EFC-LIS = 9,27 ± 2,00 mm/kg; p = 0,003), in comparison with the groups C and EFC-LIS; the diastolic diameter of the left ventricle, adjusted by BW was higher in the groups EFC e EFC-LIS (C = 18,42 ± 3,57, EFC = 22,94 ± 1,98, EFC-LIS = 22,05 ± 1,30 mm/kg; p = 0,003); the relationship EPP/DDVE was smaller in the group EFC-LIS in relation to the control (C = 0,20 (0,18-0,23), EFC = 0,15 (0,14-0,18), EFC-LIS = 0,14 (0,14-0,18); p = 0,026). The group EFC presented smaller ejection fraction... (Complete abstract click electronic access below)

<p>The combination of a severe systemic illness, corticosteroids, and neuromuscular blocking agents in patients on the mechanical ventilator often results in a condition known as Acute Quadriplegic Myopathy (AQM). While severe weakness of all spinal nerve innervated muscles is known to be a significant clinical characteristic of the disease, this symptom is typically not recognized until the disease has progressed to an advanced stage. End result effects have been classified, which include the loss of the thick filament, or myosin heavy chain, an in-excitable muscle membrane, and an up-regulation of protein degradation; however, there is little known about the acute stage of AQM. This project has focused on understanding the underlying mechanisms of AQM, specifically in regard to protein synthesis, both at the mRNA and nuclear transcription levels. To study the early stages of the disease two animal models have been developed: rat and pig. Further, we have examined AQM muscle tissue, to investigate the similarities of our animal models to patients, as well as to study the recovery process. Particular interest was directed on the myofibrillar proteins myosin (MyHC) and actin, as they are the primary proteins involved in muscle contraction, as well as the myosin associated proteins, myosin binding protein C and H. </p><p>At the mRNA level, MyHC and actin are both down-regulated in response to AQM. The myosin binding proteins are affected differently, with H protein increasing during severe atrophy and C protein either being slightly down-regulated or unchanged. Nuclear transcription factors were also affected, with such factors as MuRF1 and MAFbx up-regulated. </p><p>Thus far results have shown that protein synthesis is altered in AQM and largely contributes to both the development and recovery of the disease. The pathways of protein synthesis may prove to be an ideal target for the prevention of AQM and/or symptom alleviation.</p>

Skeletal muscle is a heterogeneous, multinucleated, post-mitotic tissue that contains many functionally diverse fibre types that are capable of adjusting their phenotypic properties in response to altered contractile demands. This plasticity, or adaptability of skeletal muscle is largely dictated by variations in motoneuron firing patterns. For example, in response to increased tonic firing of slow motoneurons, which occurs during bouts of endurance training or chronic low-frequency stimulation (CLFS), skeletal muscle adapts by transforming from a faster to a slower phenotypic profile. CLFS is an animal model of endurance training that induces fast-to-slow fibre type transformations in the absence of fibre injury in the rat. The underlying signaling mechanisms regulating this fast-to-slow fibre type transformation, however, remain to be fully elucidated. It has been suggested that myogenic stem cells, termed satellite cells, may regulate and/or facilitate this transformational process. Therefore, the signaling mechanisms involved in CLFS-induced satellite cell activation as well as the role satellite cells may play in CLFS-induced skeletal muscle adaptation were investigated in rat. A pharmacological inhibitor of nitric oxide (NO) synthase, Nω-nitro-L-arginine methyl ester, was used to investigate CLFS-induced satellite cell activation in the absence of endogenous NO production. Results suggest that NO is required for early CLFS-induced satellite cell activation, but a yet-to-be defined pathway exists that is able to fully compensate in the absence of prolonged NO production. A novel method of satellite cell ablation (i.e. weekly focal γ-irradiation application) was used to investigate CLFS-induced skeletal muscle adaptation in the absence of a viable satellite cell population. Myosin heavy chain (MHC), an important structural and regulatory protein component of the contractile apparatus, was used as a cellular marker of the adaptive response to CLFS. Findings suggest that satellite cell activity may be required for early fast-to-slow MHC-based transformations to occur at the protein level without delay in the fast fibre population, and may also play an obligatory role in the final transformation from fast type IIA to slow type I fibres. Interestingly, additional results show that NO appears to be a key mediator of MHC isoform gene expression during CLFS-induced fast-to-slow fibre type transformations.

The combination of a severe systemic illness, corticosteroids, and neuromuscular blocking agents in patients on the mechanical ventilator often results in a condition known as Acute Quadriplegic Myopathy (AQM). While severe weakness of all spinal nerve innervated muscles is known to be a significant clinical characteristic of the disease, this symptom is typically not recognized until the disease has progressed to an advanced stage. End result effects have been classified, which include the loss of the thick filament, or myosin heavy chain, an in-excitable muscle membrane, and an up-regulation of protein degradation; however, there is little known about the acute stage of AQM. This project has focused on understanding the underlying mechanisms of AQM, specifically in regard to protein synthesis, both at the mRNA and nuclear transcription levels. To study the early stages of the disease two animal models have been developed: rat and pig. Further, we have examined AQM muscle tissue, to investigate the similarities of our animal models to patients, as well as to study the recovery process. Particular interest was directed on the myofibrillar proteins myosin (MyHC) and actin, as they are the primary proteins involved in muscle contraction, as well as the myosin associated proteins, myosin binding protein C and H. At the mRNA level, MyHC and actin are both down-regulated in response to AQM. The myosin binding proteins are affected differently, with H protein increasing during severe atrophy and C protein either being slightly down-regulated or unchanged. Nuclear transcription factors were also affected, with such factors as MuRF1 and MAFbx up-regulated. Thus far results have shown that protein synthesis is altered in AQM and largely contributes to both the development and recovery of the disease. The pathways of protein synthesis may prove to be an ideal target for the prevention of AQM and/or symptom alleviation.

Das Chemokine SDF-1α und sein Rezeptor CXCR4 sind in eine Vielzahl biologischer Prozesse, wie der Organogenese, der Hämatopoese und der Immunantwort involviert. Die Entdeckung des alternativen SDF-1α-Rezeptors CXCR7 bewirkte eine erneute Untersuchung der Funktion des SDF-1-Systems in diesen Vorgängen. CXCR7 ist in der Lage, je nach Gewebe- oder Zelltyp, als \"Scavenger\"-Rezeptor, Modulator des CXCR4 oder selbstständig aktiver Rezeptor zu agieren. In dieser Arbeit wurde untersucht, inwiefern beide Rezeptoren im Verlauf der Entwicklung der Muskulatur exprimiert werden, welche Aufgabe sie dabei übernehmen und ob sich Rückschlüsse auf die Muskelregeneration daraus ableiten lassen. Hierfür erfolgten in vitro-Untersuchungen an C2C12-Zellen und die anschließende Analyse der Expression von CXCR4, CXCR7 und SDF-1α in der sich entwickelnden Gliedmaßenmuskulatur von Wildtyp- und mdx-Mäusen. Die Untersuchung von C2C12-Zellen zeigte in allen Differenzierungsstadien eine detektierbare Menge von CXCR4 und eine zunehmende Expression des CXCR7. Die Behandlung der Zellen mit SDF-1α führte zu einer Phosphorylierung von Erk1/2 und PKCζ/λ und hemmte gleichzeitig deren Differenzierung. Nach einer Blockierung des CXCR4 mit seinem pharmakologischen Antagonist AMD3100 oder nach Hemmung der Expression durch spezifische siRNA blieb die Aktivierung des Signalweges aus und der hemmende Einfluss des SDF-1α auf die Differenzierung verschwand vollständig. Im Gegensatz dazu blieben nach der pharmakologischen Blockierung oder durch siRNA vermittelten Expressionshemmung des CXCR7 alle SDF-1α induzierten Effekte vollständig erhalten. Eine Untersuchung des Signalweges am dritten Tag der Differenzierung zeigte keine Aktivierung von Erk1/2. Ebenso blieb Erk1/2 nach einer Hemmung der Expression des CXCR4 unphosphoryliert. Im Gegensatz dazu fand nach einer Hemmung der Expression des CXCR7 mit spezifischer siRNA erneut eine Aktivierung des Signalweges statt. Weiterhin konnte in vivo festgestellt werden, dass die Expression des CXCR4 in der Muskulatur während der embryonalen Entwicklung am höchsten ist und bereits kurz nach der Geburt stark abnimmt, wenn die sekundäre Muskelentwicklung abgeschlossen ist. Die Expression des CXCR7 hingegen steigt perinatal an und bleibt bis zum Erwachsenenalter bestehen. Zusammengefasst zeigen diese Ergebnisse, dass CXCR4 aktiv das Signalgeschehen von SDF-1α in der Myogenese vermittelt und somit zur Differenzierungshemmung von Myoblasten beiträgt. CXCR7 hingegen wirkt als passiver SDF-1α-Scavenger und induziert somit durch eine Modulierung der extrazellulären SDF-1α-Konzentration die Differenzierung. In Übereinstimmung mit der Rolle des SDF-1α-Systems bei der Muskelentwicklung, konnte eine kontinuierliche SDF-1α- Expression im Bindegewebe um pränatale und im Endomysium von postnatalen und adulten Muskelfasern festgestellt werden. Diese SDF-1α-Expression stieg ebenso wie die CXCR4-Expression bei der Analyse der Muskulatur von dystrophin-defizienten Mäusen an und zeigte somit, dass dieses System auch für die Proliferation von Muskelvorläuferzellen in der regenerativen Muskulatur eine wichtige Rolle spielt. Bemerkenswerter Weise hatte diese Muskeldystrophie keinen Einfluss auf die Expression des CXCR7 und beeinflusst vermutlich dessen Funktion über einen anderen Mechanismus. Durch die offensichtlich enge Kontrolle von Muskelentwicklung und Regeneration durch CXCR4, CXCR7 und deren Liganden SDF-1α, bilden diese ein vielversprechendes therapeutisches Ziel für bestimmte Muskelerkrankungen. / The chemokine, SDF-1α, and its receptor, CXCR4, are assumed to control a multitude of biological processes such as organogenesis, haematopoesis, and immune responses. The previous demonstration that SDF-1α additionally binds to the chemokine receptor, CXCR7, currently urges a re-evaluation of the function of the SDF-1 system in these processes. In fact, depending on the tissue and cell type, CXCR7 either acts as a scavenger receptor, a modulator of CXCR4 or an independent active receptor. This thesis is dedicated to answer the following questions: Are both SDF-1α receptors expressed during muscle development? What is the actual function of these receptors during myogenesis? Is there a role of the SDF-1 system in muscle regeneration? To adress these issues both in vitro studies with the myoblast cell line, C2C12, as well as in vivo analyses on the expression of CXCR4, CXCR7 and SDF-1α in developing and regenerating limb muscles have been performed. At all stages of differentiation, C2C12 cells exhibited measurable amounts of CXCR4. In addition, in the course of differentiation C2C12 cells showed increasing expression levels of CXCR7. Treatment of the cells with SDF-1α resulted in the phosphorylation of Erk1/2 and PKCζ/λ and subsequently blocked their myogenic differentiation. Following inactivation of CXCR4 either by its antagonist, AMD3100, or by specific siRNA, SDF-1α failed to activate both pathways and in addition no longer inhibited the myogenic differentiation of C2C12 cells. By contrast, inactivation of CXCR7 remained without effects on SDF-1α-induced cell signalling and resulting inhibitory effects on myogenic differentiation. Interestingly, SDF-1α also failed to activate Erk1/2 signalling in differentiated C2C12 cells. Cell signalling in differentiated C2C12 cells was, however, restored following inhibition of CXCR7 expression, but not following inhibition of CXCR4 expression. The in vivo analysis further revealed that in limb muscles expression of the CXCR4 is highest during embryonic development with a decrease in expression levels shortly after birth when secondary muscle development is completed. Vice versa, expression levels of CXCR7 increased perinatally and remained high into adulthood. In summary, these findings unravel that CXCR4 actively mediates SDF-1α-signalling during myogenesis. The findings further provide evidence that CXCR7 acts as a scavenger receptor during myogenesis which controls myogenic differentiation by modulating extracellular SDF-1α concentration. In further agreement with a major role of SDF-1α in muscle development, SDF-1α is continously expressed by the endomysium of postnatal and adult muscle fibers. Moreover, expression of SDF-1α as well as CXCR4 is massively increased in muscles of dystrophin-deficient mice further implying that the SDF-1 system plays an equally important role during muscle development and regeneration. The pivotal role of SDF-1α in muscle development and regeneration points to the SDF-1 system as a promising therapeutical target for certain muscle diseases.

No description available.

Tendon transfer surgery is used to improve the hand function of patients with nerve injuries, spinal cord lesions, cerebral palsy (CP), stroke, or muscle injuries. The tendon of a muscle, usually with function opposite that of the lost muscle function, is transferred to the tendon of the deficient muscle. The aim is to balance the wrist and fingers to achieve better hand function. The position, function, and length at which the donor muscle is sutured is essential for the outcome for the procedure. In these studies the significance of the transferred muscle’s morphology, length and apillarization was investigated using both animal and human models. Immunohistochemical, biochemical, and laser diffraction techniques were used to examine muscle structure. In animal studies (rabbit), the effects of immobilization and of tendon transfers at different muscle lengths were analyzed. Immobilization of highly stretched muscles resulted in fibrosis and aberrant regeneration. A greater pull on the tendon while suturing a tendon transfer resulted in larger sarcomere lengths as measured in vivo. On examination of the number of sarcomeres per muscle fiber and the sarcomere lengths after 3 weeks of immobilization and healing time, we found a cut-off point up to which the sarcomerogenesis was optimal. Transfer at too long sarcomere lengths inhibited adaptation of the muscle to its new length, probably resulting in diminished function. In human studies we defined the sarcomere lengths of a normal human flexor carpi ulnaris muscle through the range of motion, and then again after a routinely performed tendon transfer to the finger extensor. A calculated model illustrated that after a transfer the largest force was predicted to occur with the wrist in extension. Morphological studies of spastic biceps brachii muscle showed, compared with control muscle, smaller fiber areas and higher variability in fiber size. Similar changes were also found in the more spastic wrist flexors comparing with wrist extensors in children with CP. In flexors, more type 2B fibers were found. These observations could all be due to the decreased use in the spastic limb, but might also represent a specific effect of the spasticity. In children and adults with spasticity very small fibers containing developmental myosin were present in all specimens, while none were found in controls. These fibers probably represent newly formed fibers originating from activated satellite cells. Impaired supraspinal control of active motion as well as of spinal reflexes, both typical of upper motor syndrome, could result in minor eccentric injuries of the muscle, causing activation of satellite cells. Spastic biceps muscles had fewer capillaries per cross-sectional area compared to age-matched controls, and also a smaller number of capillaries around each fiber. Nevertheless, the number of capillaries related to the specific fiber area was normal, and hence the spastic fibers are sufficiently supplied with capillaries. This study shows that the length of the muscle during tendon transfer is crucial for optimization of force output. Laser diffraction can be used for accurate measurement of sarcomere length during tendon transfer surgery. Wrist flexor muscles have more morphological alterations typical of spasticity compared to extensors.

Before major athletic events, a taper is often prescribed to facilitate recovery and enhance performance. However, it is unknown which taper model is most effective for peaking maximal strength and positively augmenting skeletal muscle. Thus, the purpose of this study was to compare performance outcomes and skeletal muscle adaptations following a step vs. an exponential taper in strength athletes. Sixteen powerlifters (24.0 ± 4.0 years, 174.4 ± 8.2 cm, 89.8 ± 21.4 kg) participated in a 6-week training program aimed at peaking maximal strength on back squat [initial 1-repetition-maximum (1RM): 174.7 ± 33.4 kg], bench press (118.5 ± 29.9 kg), and deadlift (189.9 ± 41.2 kg). Powerlifters were matched based on relative maximal strength, and randomly assigned to either (a) 1-week overreach and 1-week step taper or (b) 1-week overreach and 3-week exponential taper. Athletes were tested pre- and post-training on measures of body composition, jumping performance, isometric squat, and 1RM. Whole muscle size was assessed at the proximal, middle, and distal vastus lateralis using ultrasonography and microbiopsies at the middle vastus lateralis site. Muscle samples ( = 15) were analyzed for fiber size, fiber type [myosin-heavy chain (MHC)-I, -IIA, -IIX, hybrid-I/IIA] using whole muscle immunohistochemistry and single fiber dot blots, gene expression, and microRNA abundance. There were significant main time effects for 1RM squat ( < 0.001), bench press ( < 0.001), and deadlift, ( = 0.024), powerlifting total ( < 0.001), Wilks Score ( < 0.001), squat jump peak-power scaled to body mass ( = 0.001), body mass ( = 0.005), fat mass ( = 0.002), and fat mass index ( = 0.002). There were significant main time effects for medial whole muscle cross-sectional area (mCSA) ( = 0.006) and averaged sites ( < 0.001). There was also a significant interaction for MHC-IIA fiber cross-sectional area (fCSA) ( = 0.014) with comparisons revealing increases following the step-taper only ( = 0.002). There were significant main time effects for single-fiber MHC-I% ( = 0.015) and MHC-IIA% ( = 0.033), as well as for MyoD ( = 0.002), MyoG ( = 0.037), and miR-499a ( = 0.033). Overall, increases in whole mCSA, fCSA, MHC-IIA fCSA, and MHC transitions appeared to favor the step taper group. An overreach followed by a step taper appears to produce a myocellular environment that enhances skeletal muscle adaptations, whereas an exponential taper may favor neuromuscular performance.

La myosine est une protéine motrice impliquée dans la contraction du muscle lisse. Un de ces isoformes, appelé (+)insert lui procure une vélocité accrue. L’objectif de cette étude était d’évaluer la contribution de cet isoforme au bronchospasme observé chez les chevaux atteints de souffle, un modèle d’asthme humain. Nous avons procédé à l’analyse de l’expression génique de l’isoforme (+)insert dans les voies respiratoires de chevaux issus de 3 cohortes afin d’évaluer 1) la présence de cet isoforme chez les chevaux atteints de souffle ; 2) la réversibilité de son expression avec 2 traitements usuels (corticostéroïdes inhalés et retrait antigénique); et 3) la cinétique de réapparition de l’isoforme suite à une période de rémission de la maladie. Les résultats révèlent 1) une expression augmentée de l’isoforme (+)insert dans l’ensemble de l’arbre bronchique des chevaux atteints de souffle en exacerbation comparée aux contrôles et aux chevaux en rémission ; 2) les deux traitements conduisent à une réduction de l’expression de l’isoforme, mais l’administration de corticostéroïdes mène à une diminution plus rapide que celle induite par le retrait antigénique; et 3) une période de 30 jours ou plus d'exposition antigénique est nécessaire pour la réapparition de l’isoforme (+)insert dans l’arbre bronchique des chevaux atteints de souffle. Cette étude montre pour la première fois une modulation et une réversibilité de l’expression de l'isoforme (+)insert de la myosine en fonction du statut médical du sujet. Les données suggèrent que cet isoforme pourrait faire partie d’un mécanisme protecteur activé en réponse à une exposition antigénique prolongée. / Myosin is a motor protein implicated in smooth muscle contraction. The (+)insert isoform doubles smooth muscle velocity. The aim of the study was to evaluate the contribution of the fast contracting myosin isoform to bronchospasm in heaves-affected horses as model of human asthma. Gene expression analysis of the (+)insert myosin isoform in equine airways was performed in three different cohorts to evaluate 1) its presence and anatomical location in heaves-affected horses; 2) the reversibility of its expression with two common therapies (inhaled corticosteroids and antigen avoidance); and 3) its kinetics of reappearance following a chronic antigen exposure. Results showed 1) a significantly increased expression of the (+)insert isoform at all levels of the bronchial tree of horses with heaves in clinical exacerbation when compared to control horses and heaves-affected horses in clinical remission; 2) both treatments reduced the fast isoform expression in horses’ lower airways, but the administration of corticosteroids led to a faster response; and 3) (+)insert isoform does not increase in airways of all horses with heaves within 30 days of antigen exposure. The study shows for the first time a modulation of the fast contracting myosin isoform with the disease status. Data also suggest that (+)insert isoform is part of a protective mechanism enhanced in response to a prolonged antigen exposure.

La myosine est une protéine motrice impliquée dans la contraction du muscle lisse. Un de ces isoformes, appelé (+)insert lui procure une vélocité accrue. L’objectif de cette étude était d’évaluer la contribution de cet isoforme au bronchospasme observé chez les chevaux atteints de souffle, un modèle d’asthme humain. Nous avons procédé à l’analyse de l’expression génique de l’isoforme (+)insert dans les voies respiratoires de chevaux issus de 3 cohortes afin d’évaluer 1) la présence de cet isoforme chez les chevaux atteints de souffle ; 2) la réversibilité de son expression avec 2 traitements usuels (corticostéroïdes inhalés et retrait antigénique); et 3) la cinétique de réapparition de l’isoforme suite à une période de rémission de la maladie. Les résultats révèlent 1) une expression augmentée de l’isoforme (+)insert dans l’ensemble de l’arbre bronchique des chevaux atteints de souffle en exacerbation comparée aux contrôles et aux chevaux en rémission ; 2) les deux traitements conduisent à une réduction de l’expression de l’isoforme, mais l’administration de corticostéroïdes mène à une diminution plus rapide que celle induite par le retrait antigénique; et 3) une période de 30 jours ou plus d'exposition antigénique est nécessaire pour la réapparition de l’isoforme (+)insert dans l’arbre bronchique des chevaux atteints de souffle. Cette étude montre pour la première fois une modulation et une réversibilité de l’expression de l'isoforme (+)insert de la myosine en fonction du statut médical du sujet. Les données suggèrent que cet isoforme pourrait faire partie d’un mécanisme protecteur activé en réponse à une exposition antigénique prolongée. / Myosin is a motor protein implicated in smooth muscle contraction. The (+)insert isoform doubles smooth muscle velocity. The aim of the study was to evaluate the contribution of the fast contracting myosin isoform to bronchospasm in heaves-affected horses as model of human asthma. Gene expression analysis of the (+)insert myosin isoform in equine airways was performed in three different cohorts to evaluate 1) its presence and anatomical location in heaves-affected horses; 2) the reversibility of its expression with two common therapies (inhaled corticosteroids and antigen avoidance); and 3) its kinetics of reappearance following a chronic antigen exposure. Results showed 1) a significantly increased expression of the (+)insert isoform at all levels of the bronchial tree of horses with heaves in clinical exacerbation when compared to control horses and heaves-affected horses in clinical remission; 2) both treatments reduced the fast isoform expression in horses’ lower airways, but the administration of corticosteroids led to a faster response; and 3) (+)insert isoform does not increase in airways of all horses with heaves within 30 days of antigen exposure. The study shows for the first time a modulation of the fast contracting myosin isoform with the disease status. Data also suggest that (+)insert isoform is part of a protective mechanism enhanced in response to a prolonged antigen exposure.