Contractile Capacity Research Articles

Long non-coding RNA in regulation of plasticity of vascular smooth muscle cells

Phenotypic plasticity of vascular smooth muscle cells (VSMCs) is a functional property that is essential for vascular remodeling in vessel injury healing. During phenotypic switch, quiescent VSMCs loss contractile capacity but acquire ability to proliferate and migrate to the injured site where they differentiate again to the quiescent state. However, in pathological conditions such as endothelial dysfunction or atherosclerosis, phenotypic changes in arterial VSMCs become deregulated leading to elevated VSMC dedifferentiation, proliferation, excessive extracellular matrix deposits, and intimal thickening. VSMC hyperplasia is a complex mechanism that is coordinated by a network of various regulatory factors. Long non-coding (lnc)RNAs represent an important part of this regulatory network. Some of lncRNAs are involved in VSMC differentiation, apoptosis, and maintenance of VSMC quiescence, while other lncRNAs promote VSMC dedifferentiation, proliferation, and motility. In this review, we characterize these RNAs and their function in the context of possible involvement to atherosclerosis. Normal 0 false false false EN-GB X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:Table Normal; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:Calibri,sans-serif; mso-bidi-font-family:Times New Roman; mso-ansi-language:EN-GB; mso-fareast-language:EN-GB;}

The impact of nine weeks swimming exercise on heart function in hypertensive and normotensive rats: role of cardiac oxidative stress.

The purpose of this study was to estimate the effects of 9-week swimming training on cardiodynamic parameters and coronary flow in a rat model of high salt-induced hypertension with a special focus on the role of oxidative stress. Rats involved in the research were divided randomly into four groups: healthy sedentary (SA), healthy trained (TA), sedentary hypertensive (SHA) and trained hypertensive animals (THA). Trained rats were exposed to 9-week swimming training (5 days/week, 60 min/day). Additionally, in order to induce hypertension animals from SHA and THA groups were on high sodium (8% NaCl solution) diet during 4 weeks. Afterwards all rats were sacrificed and hearts were isolated and retrogradely perfused according to Langendorff technique. The following parameters of cardiac function were continuously recorded: maximum and minimum rate of pressure development in left ventricle, systolic and diastolic left ventricular pressure and heart rate. Coronary flow was measured flowmetrically. Oxidative stress markers were determined in coronary venous effluent. Our findings demonstrated that 9 weeks of swimming training led to improvement of cardiac contractility, relaxation and systolic capacity of normotensive rats, while this training protocol induced enhanced diastolic function in hypertensive conditions. More pronounced effects of exercise in alleviating oxidative stress were observed in hypertensive rats. Obvious beneficial exercise-induced cardiac adaptations provide scientific basis for further researches which would thoroughly clarify the mechanisms through which swimming training alters myocardial function both in healthy conditions and in the presence of chronic diseases.

Acute exposure to glycated proteins reduces cardiomyocyte contractile capacity.

What is the central question of this study? Does acute exposure to high molecular weight advanced glycation end products (HMW-AGEs) alter cardiomyocyte contractile function? What is the main finding and its importance? Ventricular cardiomyocytes display reduced Ca2+ influx, resulting in reduced contractile capacity, after acute exposure to HMW-AGEs, independent of activation of their receptor. Given that HMW-AGEs are abundantly present in our Western diet, a better understanding of underlying mechanisms, especially in patients already displaying altered cardiac function, should be gained for these compounds. Sustained elevated levels of high molecular weight advanced glycation end products (HMW-AGEs) are known to promote cardiac dysfunction. Recent data suggest that acutely elevated levels of AGEs occur in situations of increased oxidative stress. Whether this increase might have detrimental effects on cardiac function remains unknown. In this study, we investigated whether acute exposure to HMW-AGEs affects cardiomyocyte function via activation of their receptor (RAGE) signalling pathway. Single cardiomyocytes from the left ventricle of adult male rats were obtained by enzymatic dissociation through retrograde perfusion of the aorta. Functional experiments were performed in cardiomyocytes pre-incubated with or without an anti-RAGE antibody. Unloaded cell shortening and L-type Ca2+ current amplitude were evaluated in the presence or absence of HMW-AGEs (200μgml-1 ). Expression of RAGE, c-Jun N-terminal kinase (JNK) and phosphorylated JNK (pJNK) were assessed by western blot. Experiments were performed at room temperature. After 4min application of HMW-AGEs, unloaded cell shortening was significantly reduced. This impaired contractile function was related to reduced Ca2+ influx. These alterations were also observed in cardiomyocytes pre-incubated with anti-RAGE antibody. Our study demonstrates that acute exposure to elevated levels of HMW-AGEs leads to direct and irreversible cardiomyocyte dysfunction, independent of RAGE activation.

KGF-1 accelerates wound contraction through the TGF-β1/Smad signaling pathway in a double-paracrine manner

KGF-1 plays an important role in the wound healing process. Loss of the KGF-1 gene in diabetic mice attenuated the process of wound contraction, suggesting that KGF-1 contributes to wound contraction. However, the mechanism remains unclear. To investigate the role of KGF-1 in diabetic wound contraction, we established a keratinocyte-fibroblast co-culture system. Concentrations of transforming growth factor β1 (TGF-β1) in conditioned supernatant treated with KGF-1 (KGF-1 group), tk;4KGF-1-neutralizing antibody (anti-KGF-1 group), TGF-β1 (TGF-β1tk;1 group), KGF-1 and TGF-β1-neutralizing antibody (KGF-1 + anti-TGF-β1 group) were tested by ELISA. Conditioned medium was added to fibroblast-populated collagen lattice (FPCL) to investigate the effect of KGF-1 on fibroblastqj contraction. TGF-β1, Col-I, p-Smad2, p-Smad3, and α-smooth muscle actin (α-SMA) were examined by Western blotting. A diabetic rat wound model was utilized to evaluate wound morphology, histology, immunohistochemistry, and protein expression in wound tissue after treatment with KGF-1. ELISA assays revealed that the concentration of TGF-β1 in the conditioned supernatant in the KGF-1 group was significantly higher. The contractile capacity of FPCL stimulated by conditioned medium derived from the KGF-1 group was significantly elevated; however, the contractile activity of FPCL induced by KGF-1 was attenuated by TGF-β1-neutralizing antibody. The Western blot results suggest that KGF-1 is able to stimulate TGF-β1 activation with increased Col-I, p-Smad2, p-Smad3, and α-SMA expression. Diabetic wounds treated with KGF-1 had a higher degree of contraction with significantly higher expression of TGF-β1, Col-I, p-Smad2, p-Smad3, and α-SMA. Our findings demonstrate that KGF-1 promotes fibroblast contraction and accelerates wound contraction via the TGF-β1/Smad signaling pathway in a double-paracrine manner.

Diaphragm ultrasonography and pulmonary function tests in patients with spinal cord injury.

Cross-sectional study. To investigate the role of ultrasonographic measurement of the diaphragm thickness on pulmonary function tests in patients with spinal cord injury (SCI). Rehabilitation center in Ankara, Turkey. A total of 42 patients (34 M, 8 F) with SCI and 20 able-bodied volunteers (8 M, 12 F) were enrolled. Patients with SCI were divided into three groups according to their neurological (injury) levels. All participants underwent ultrasonographic measurements for diaphragm thickness on both sides and spirometric tests for pulmonary functions. The thickness ratio of the diaphragm was also calculated. There were seven patients (5 M, 2 F) in C2-C4 injury group, 14 patients (12 M, 2 F) in C5-T5 group, 21 patients (14 M, 7 F) in T6-L2 group, and 20 able-bodied volunteers (8 M, 12 F). The diaphragms of C2-C4 group were thicker than those of the controls at end-inspirium on the right side (2.7 ± 0.7 mm vs. 2.0 ± 0.5 mm; p = 0.035). The thickness ratios of C2-C4 group were lower than those of controls on the right (0.8 ± 0.4 vs. 1.5 ± 0.5; p = 0.005) and left (0.8 ± 0.5 vs. 1.6 ± 0.7; p = 0.003) sides. For all the pulmonary function tests (except for FEV1/FVC); patients with SCI had worse results than controls; and among the SCI groups, the higher the injury level, the worse the results. Although patients with high-level SCI had worse pulmonary function tests and decreased the contractile capacity of the diaphragm, they had thicker diaphragm muscles than controls. This may have been due to the compensatory effect of the diaphragm (performing its maximum contraction capacity and increasing frequency of inspiration).

The “Gastrocnemius–Achilles Tendon–Calcaneus Complex”: Different Responses after Percutaneous versus Vulpius Achilles Tendon Lengthening in New Zealand White Rabbits

Background:This study aimed to describe the clinical, radiological, biomechanical, electromyographic, and histoenzymologic modifications in the “Gastrocnemius–Achilles Tendon–Calcaneus complex” caused by percutaneous Achilles tendon lengthening (PATL) versus Vulpius Achilles tendon lengthening (VATL) in New Zealand White (NZW) rabbits.Materials and Methods:Eight female NZW rabbits were used at 7 months of age. Two rabbits were euthanized before surgery for anatomical dissection, three underwent PATL (two bilateral and one unilateral), and the three others underwent VATL (two bilateral and one unilateral). Clinical examination, biomechanics, electromyography, standard radiographs and magnetic resonance imaging (MRI), and histology and histoenzymology were assessed after surgery.Results:At the end of the experiment, the subjects showed good clinical status but different functional outcomes of surgery: rabbits submitted to PATL developed permanent limp and lost their capacity to jump compared to rabbits submitted to VATL which remained able to ambulate and jump normally. Standard radiographs and MRI showed that PATL led to significantly greater increase in dorsal or anterior flexion of the tibiotarsal angle (TT angle) compared to VATL, whereas electromyographic and histoenzymologic observations of muscle unit showed little or no variation between the two groups of operated rabbits.Conclusions:Although PATL leads to greater improvement in dorsal or anterior flexion (TT angle) of the rabbit ankle compared to VATL, it has negative effects on functional outcome as it reduces the contractile capacity of the rabbit muscle unit, ultimately impairing the ability to ambulate and jump.

Enhancing the Work Capacity of Electrochemical Artificial Muscles by Coiling Plies of Twist-Released Carbon Nanotube Yarns

Twisted-yarn-based artificial muscles can potentially be used in diverse applications, such as valves in microfluidic devices, smart textiles, air vehicles, and exoskeletons, because of their high torsional and tensile strokes, high work capacities, and long cycle life. Here, we demonstrate electrochemically powered, hierarchically twisted carbon nanotube yarn artificial muscles that have a contractile work capacity of 3.78 kJ/kg, which is 95 times the work capacity of mammalian skeletal muscles. This record work capacity and a tensile stroke of 15.1% were obtained by maximizing yarn capacitance by optimizing the degree of inserted twist in component yarns that are plied until fully coiled. These electrochemically driven artificial muscles can be operated in reverse as mechanical energy harvesters that need no externally applied bias. In aqueous sodium chloride electrolyte, a peak electrical output power of 0.65 W/kg of energy harvester was generated by 1 Hz sinusoidal elongation.

MiR-1246 as a therapeutic target in oral submucosa fibrosis pathogenesis

Oral submucous fibrosis (OSF) is a precancerous condition of oral cancer with a complex etiology. Our previous work has demonstrated that non-coding RNA miR-1246 contributes to the cancer stemness of oral cancer. In the current study, we sought to investigate the effect of the inhibition of miR-1246 on the oral fibrogenesis. The expression levels of miR-1246 in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were examined by qRT-PCR. Collagen gel contraction and migration assays were conducted to evaluate the myofibroblast activities. The relationship between miR-1246 and type I collagen was assessed and the protein expression of type I collagen was determined by Western blot. MiR-1246 expression was upregulated in both OSF specimen and fBMFs compared to the normal counterparts. Inhibition of miR-1246 successfully suppressed the myofibroblast activities, including collagen gel contractility and migration capacity. Moreover, the expression of miR-1246 was positively correlated with type I collagen and the expression of type I collagen was abrogated by repression of miR-1246. MiR-1246 is not only critical to the maintenance of oral stemness but also important to the activation of myofibroblasts. Our results showed that miR-1246 is positively associated with the type I collagen, which may be a downstream effector of miR-1246 and responsible for the fibrosis effect on fBMFs.

Consequence of Desmin gene mutation on development of chronic hypoxic pulmonary hypertension in mice

Desmin deficiency is responsible for various forms of skeletal and cardiac disorders. However, role of desmin in the normal and pathological pulmonary vasculature remains unknown. To investigate whether desmin deficiency affects pulmonary circulation in normoxic and hypoxic conditions. Desmin-deficient mice (Des-/-) and their littermate Des+/+ (controls) aged 2–4 months were exposed to chronic hypoxia (9% O2, 2 weeks) or normoxia. Cardiac function was assessed by closed-chest echocardiography and right ventricle (RV) hemodynamics combined with measurements of Fulton Index and muscularization of pulmonary arteries (PA). Contractile properties of intrapulmonary arteries were measured by using an arteriography. Heart and lung phenotype were determined by using standard techniques of histology, immunostaining, immunoblot and RT-qPCR analysis. Under normal conditions Des-/- mice developed cardiomyopathy with alteration of both left ventricle (LV) and RV functions. Left Heart Disease was characterized by ventricular dilatation, decreased Ejection Fraction and Strain Rate in agreement with extreme transmural fibrosis and cardiomyocytes hypertrophy. RV dysfunction was evidenced by an increase of RV systolic pressure (RVSP) and PA muscularization. After exposure to hypoxia, LV function was globally not modified in both Des-/- and Des+/+ mice. RV was similarly affected in both strains, though the increase of RV weight, RVSP and PA muscularization were higher in Des-/- mice. Conversely, contractile capacities of PA were not modified in Des-/- mice in normoxia. Under hypoxia, we recorded modifications of several contractile, structural and Ca2 ± handling proteins in PA - smooth muscle cells (SMC). Our results indicate that desmin can be replaced by vimentin in SMC without loss of function. However, clinical features of desminopathies can also include pulmonary hypertension with PA remodeling and higher RV dysfunction.

Fundamental Roles of Axial Stretch in Isometric and Isobaric Evaluations of Vascular Contractility.

Vascular smooth muscle cells (VSMCs) can regulate arterial mechanics via contractile activity in response to changing mechanical and chemical signals. Contractility is traditionally evaluated via uniaxial isometric testing of isolated rings despite the in vivo environment being very different. Most blood vessels maintain a locally preferred value of in vivo axial stretch while subjected to changes in distending pressure, but both of these phenomena are obscured in uniaxial isometric testing. Few studies have rigorously analyzed the role of in vivo loading conditions in smooth muscle function. Thus, we evaluated effects of uniaxial versus biaxial deformations on smooth muscle contractility by stimulating two regions of the mouse aorta with different vasoconstrictors using one of three testing protocols: (i) uniaxial isometric testing, (ii) biaxial isometric testing, and (iii) axially isometric plus isobaric testing. Comparison of methods (i) and (ii) revealed increased sensitivity and contractile capacity to potassium chloride and phenylephrine (PE) with biaxial isometric testing, and comparison of methods (ii) and (iii) revealed a further increase in contractile capacity with isometric plus isobaric testing. Importantly, regional differences in estimated in vivo axial stretch suggest locally distinct optimal biaxial configurations for achieving maximal smooth muscle contraction, which can only be revealed with biaxial testing. Such differences highlight the importance of considering in vivo loading and geometric configurations when evaluating smooth muscle function. Given the physiologic relevance of axial extension and luminal pressurization, we submit that, when possible, axially isometric plus isobaric testing should be employed to evaluate vascular smooth muscle contractile function.

Autocrine CTHRC1 activates hepatic stellate cells and promotes liver fibrosis by activating TGF-β signaling.

BackgroundHepatic fibrosis is caused by chronic liver injury and may progress toward liver cirrhosis, and even hepatocellular carcinoma. However, current treatment is not satisfactory. Therefore, there is a mandate to find novel therapeutic targets to improve therapy, and biomarkers to monitor therapeutic response.MethodsLiver fibrosis was induced by carbon tetrachloride (CCl4) or thioacetamide (TAA) in wild type (WT) or CTHRC1−/− mice, followed by immunofluorescence and immunohistochemical analyses. CTHRC1 monoclonal antibody (mAb) was used to abrogate the effect of CTHRC1 in vitro and in vivo.ResultsHere, we reported that collagen triple helix repeat containing 1 (CTHRC1), a secreted protein derived from hepatic stellate cells (HSCs), was significantly up-regulated in fibrotic liver tissues. CTHRC1 promoted HSCs transformation from a quiescent to an activated state, and enhanced migratory or contractile capacities of HSCs by activating TGF-β signaling. Meanwhile, CTHRC1 competitively bound to Wnt noncononical receptor and promoted the contractility but not activation of HSCs. CCl4 or TAA-induced liver fibrosis was attenuated in CTHRC−/− mice compared with littermate control, while a monoclonal antibody of CTHRC1 suppressed liver fibrosis in WT mice treated with CCl4 or TAA.InterpretationWe demonstrated that CTHRC1 is a new regulator of liver fibrosis by modulating TGF-β signaling. Targeting CTHRC1 could be a promising therapeutic approach, which can suppress TGF-β signaling and avoid the side effects caused by directly targeting TGF-β. CTHRC1 could also be a potential biomarker for monitoring response to anti-fibrotic therapy.FundThis study was supported by the National Natural Science Foundation of China (ID 81672358, 81871923, 81872242, 81802890), the Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (ID 20181708), the Natural Science Foundation of Shanghai (ID 17ZR1428300, 18ZR1436900), and Shanghai Municipal Health Bureau (ID 2018BR32). The funders did not play a role in manuscript design, data collection, data analysis, interpretation nor writing of the manuscript.

Differential Organization of Airway Smooth Muscle Cells on Tubular Surface as A Novel Mechanobiology Mechanism of Airway Tissue Morphogenesis

Airway smooth muscle cells (ASMCs) exists within the bronchial airway wall in a form of spirally winding bundles [1]. This pattern emerges early during embryonic development and is involved in airway branching [2], providing the airway appropriate contractile capacity and resistance to circumferential tension in health or causing excessive airway narrowing in disease such as asthma. Despite its importance, the cause of ASMCs self-organization remains largely a mystery. Previously, we have demonstrated in 2D that ASMCs can sense the curvature in their microenvironment and change behaviors in differentiation, orientation and migration accordingly [3]. Here we further explore in 3D microenvironment how ASMCs collectively behave on tubular surface of substrate, which more closely mimics the confined curved space of small diameter airways. Using time lapse live cell microscopic video imaging and fluorescence confocal microscopy, we observed, to our surprise, two distinct behaviors of self-organization of ASMCs, depending whether on the concave (inner) or convex (outer) side of the tubular substrate. On concave side, cells always adapted to the curved surface into aligned arrangement perpendicular to the longitudinal axis of the tubular substrate. On convex side, the cells eventually aligned with an angle relative to the longitudinal axis, and the angle was dependent on the tubular curvature. Interestingly, this seems to be a unique phenomenon associated with ASMCs, as other cell types showed no such behaviors. Furthermore, this phenomenon appeared to be either promoted or impaired if the ASMCs were either modulated towards a more contractile phenotype or pharmacologically relaxed. The self-organization also occurred with distinct cytoskeleton remodeling, suggesting the origin of its driving force. Thus, it reveals a novel mechanobiology mechanism for airway tissue morphogenesis/regulation, which may be important for better understanding airway pathophysiology but also useful in development of new technique for airway disease treatment such as tissue regeneration.

INFLUENCE OF THE TRANSFERRED SYPHILITIC INFECTION ON THE COURSE OF PREGNANCY, CHILDBIRTH AND THE STATE OF NEWBORNS

Introduction: The article presents information about the peculiarities of the course of pregnancy and childbirth in women with a syphilitic infection in the anamnesis. The peculiarities of the state of newborn babies born from mothers who have suffered syphilis are described. To date, the incidence of syphilis in Ukraine has a clear tendency to decline, but still remains quite high. The maximum incidence of syphilis is observed in women aged 15-20 years. The combination of pregnancy and syphilitic infection in an anamnesis is an unfavorable factor in regard to high risk of perinatal complications, the frequency of which does not tend to decrease. The aim - study the features of the course of pregnancy and childbirth in women with a syphilitic infection in the anamnesis, the evaluation of the state of newborns. Materials and methods: A prospective examination of 57 healthy women and their newborns (control group) and 60 pregnant women with a history of syphilitic infection (the main group) had been conducted. All pregnant women had undergone ultrasound examination, including feto- and placentometry, an estimate of the amount of amniotic fluid. The effect of the transferred syphilis on the state of the newborn had been assessed in accordance with the results of the clinical examination of an anthropometric data, including an Apgar score. Results: It is stated that the incidence of latent (41,66%) and forms with a prolonged course (20,00%) of syphilitic infection. The threat of premature childbirth was almost 3,5 times higher than in women with syphilis, cases of an anemia in pregnant women - 2 times, hypertensive disorders of pregnant women were 2,4 times more common in women of the main group, fetal development retardation syndrome 6,4 times, while a greater percentage of this disorder was recorded among women in the main group who were ill with latent forms and suffered secondary recurrent syphilis (35%). In 20% of the cases, pregnancy in women with syphilis has been completed by the cesarean section, an abnormality of the contractile capacity of the uterus was significantly higher - 23,33%. The adaptive capacity of the newborns in the main group has been significantly lower, compared to the control group. Conclusions: Syphilitic infection in the anamnesis complicates the course of pregnancy with numerous pathological conditions. Syphilitic infection, borne before pregnancy, affects not only the course of pregnancy, but also the course of childbirth and the postpartum period. The pathological conditions in infants are due to a decrease in resistance to birth stress, early depletion of adaptive resources of newborns under the influence of a syphilitic infection of the mother. In children who have experienced chronic intrauterine hypoxia, the risk of hemorrhagic syndrome is significantly higher due to increased permeability of the vascular wall. Such children have a tendency to develop neurological disorders and respiratory system lesions.

Features of lesion of the cardiovascular system in patients with acute brucellosis

Heart damage in acute brucellosis can determine the severity of the disease, affect the quality of life of the patient and the prognosis of the disease as a whole. The purpose of the study is the integrated assessment of the cardiovascular system (CCS) in patients with acute brucellosis on the basis of clinical and instrumental examination results. 120 patients with acute brucellosis were examined, the average age of patients was 35.9±2.8 years. In order to assess the state of the CCS, all patients were registered with the electrocardiogram in 12 standard leads, blood pressure (BP), and echocardiography. Statistical processing of the results was carried out using “STATISTICA 6.0” using parametric and non-parametric methods for evaluating the obtained results. During the study, it was found that 77.50% of patients with acute brucellosis had certain signs of abnormalities in the work of the CCS. Among clinical manifestations cardialgia is dominated by a non-ischemic nature, a marked increase in the frequency of cardiac contractions and a decrease in the level of predominantly diastolic blood pressure. Electrocardiographic changes are characterized by a predominant disruption of the function of automatism. The tendency to rhythm disturbances is confirmed by the detection of ventricular arrhythmias in them, prolongation of QT interval in some patients. Diagnosed disturbances of ventricular repolarization process, along with other changes, can be evidence of myocardial damage and its structural transformations. There was also a tendency to increase the size of the left heart, reducing the contractile capacity of the left ventricle and formation of one third of patients with diastolic dysfunction, which may be evidence of changes in the myocardium due to systemic inflammation inherent in brucellosis. Consequently, in the vast majority of patients with acute brucellosis, there are signs of lesion of the CCS that can be detected already during the routine clinical examination.

Biomechanical characterization of murine pulmonary arteries

The biomechanical properties of the major pulmonary arteries play critical roles in normal physiology as well as in diverse pathophysiologies and clinical interventions. Importantly, advances in medical imaging enable simulations of pulmonary hemodynamics, but such models cannot reach their full potential until they are informed with region-specific material properties. In this paper, we present passive and active biaxial biomechanical data for the right and left main pulmonary arteries from wild-type mice. We also evaluate the suitability of a four-fiber family constitutive model as a descriptor of the passive behavior. Despite regional differences in size, the biaxial mechanical properties, including passive stiffness and elastic energy storage, the biaxial wall stresses at in vivo pressures, and the overall contractile capacity in response to smooth muscle cell stimulation under in vivo conditions are remarkably similar between the right and left branches. The proposed methods and results can serve as baseline protocols and measurements for future biaxial experiments on murine models of pulmonary pathologies, and the constitutive model can inform computational models of normal pulmonary growth and remodeling. Our use of consistent experimental protocols and data analyses can also facilitate comparative studies in health and disease across the systemic and pulmonary circulations as well as studies seeking to understand remodeling in surgeries such as the Fontan procedure, which involves different types of vessels.

Local immunomodulation and muscle progenitor cells induce recovery in atrophied muscles in spinal cord injury patients

Objectives:Restore muscular trophism and voluntary contractile capacity through cell therapy in atrophied muscles in SCI patients.Setting:Out Patient Treatment, Universidad Maimonides, Buenos Aires, Argentina.Methods:After receiving spinal cord cell therapy and intensive rehabilitation, 7 chronic complete spinal cord injury (SCI) patients (4 people with paraplegia and 3 people with quadriplegia) regained muscular electrical activity in previously denervated territories. However, signs of severe muscular atrophy persisted. Looking to reverse chronic muscular atrophy, atrophied muscles with electrical activity were implanted with autologous type 1 macrophages (Mo1) and autologous tissue-specific T helper 1 Cells (Th1) associated with autologous muscular progenitor cells (MPC). The Mo1 and Th1 used cells were named Effector Cells (EC). Each muscle received between 6 to 8 implants, one every 6 weeks. Cellular therapy was combined with intensive rehabilitation program.Results:Sonogram and histological signs of recovery started eight weeks after the first implant. Sonograms showed progressively muscle volume increasing and gradually replacement of hyperechogenic muscle tissue by hypoechogenic muscle bands (resembling normal muscular structure). New bands were distributed parallel to the main muscle axis, along the entire muscular length. Histological samples of hypoechogenic bands showed new and normal muscular tissue. Changes were seen in 7/7 patients. Non-significant side events were detected in any patient over the 24 months of follow up.Conclusions:The results presented here suggest that the combination of immune and regenerative cell therapy may play an important therapeutic role in clinical and histological recovery of chronic muscular atrophy.

Interactive effects of osmotic stress and burrowing activity on protein metabolism and muscle capacity in the soft shell clam Mya arenaria

Bioturbators such as sediment-dwelling marine bivalves are ecosystem engineers that enhance sediment-water exchange and benthic-pelagic coupling. In shallow coastal areas, bivalves are exposed to frequent disturbance and salinity stress that might negatively affect their activity and physiological performance; however, the mechanisms underlying these effects are not fully understood. We investigated the effects of osmotic stress (low and fluctuating salinity) and repeated burrowing on aerobic and contractile capacity of the foot muscle (assessed by the activity of succinate dehydrogenase and myosin ATPase) as well as the levels of organic osmolytes (free amino acids) and biochemical markers of protein synthesis and proteolysis in key osmoregulatory and energy storing tissues (gills and hepatopancreas, respectively) in a common bioturbator, the soft shell clam Mya arenaria. Osmotic stress and exhaustive exercise altered the foot muscle capacity of soft shell clams and had a strong impact on protein and amino acid homeostasis in tissues not directly involved in locomotion. Acclimation to constant low salinity (5 practical salinity units) depleted the whole-body free amino acid pool and affected protein synthesis but not protein breakdown in the gill. In contrast, fluctuating (5–15) salinity increased protein breakdown rate, suppressed protein synthesis, caused oxidative damage to proteins in the gill and selectively depleted whole-body glycine pool. Clams acclimated to normal salinity (15) increased the aerobic capacity of the foot muscle upon repeated burrowing, whereas acclimation to low and fluctuating salinity reduced this adaptive muscle plasticity. Under the normal and low salinity conditions, exhaustive exercise induced protein conservation pathways (indicated by suppression of protein synthesis and catabolism), but this effect was disrupted by fluctuating salinity. These findings indicate that exhaustive exercise and osmotic stress interactively affect whole-body protein homeostasis and functional capacity of the foot muscle in soft shell clams which might contribute to reduced burrowing activity of bivalve bioturbators in osmotically challenging environments such as estuaries and shallow coastal zones.

Maladaptive aortic remodeling in hypertension associates with dysfunctional smooth muscle contractility.

Intramural cells are responsible for establishing, maintaining, and restoring the functional capability and structural integrity of the aortic wall. In response to hypertensive loading, these cells tend to increase wall content via extracellular matrix turnover in an attempt to return wall stress and/or material stiffness toward homeostatic values despite the elevated pressure. Using a common rodent model of induced hypertension, we found marked mouse-to-mouse differences in thoracic aortic remodeling over 2-4 wk of pressure elevation, with mechanoadaptation in some but gross maladaptation in most mice despite the same experimental conditions and overall genetic background. Consistent with our hypothesis, we also found a strong correlation between maladaptive aortic remodeling and a dysfunctional ability of the vessel to vasoconstrict, with maladaptation often evidenced by marked adventitial fibrosis. Remarkably, mouse-to-mouse variability did not correlate with the degree or duration of pressure elevation over the 2- to 4-wk study period. These findings suggest both a need to study together the structure, mechanical properties, and function across layers of the wall when assessing aortic health and a need for caution in using common statistical comparisons across small seemingly well-defined groups that may mask important underlying individual responses, an area of investigation that demands increasing attention as we move toward an era of precision diagnosis and patient care. NEW & NOTEWORTHY There are three primary findings. Marked mouse-to-mouse differences exist in large vessel hypertensive remodeling in an otherwise equivalent cohort of animals. The degree of maladaptation correlates strongly with decreases in smooth muscle contractile capacity. Finally, short-term maladaptive remodeling is independent of the precise degree or duration of the pressure elevation provided that thresholds are exceeded. Therapeutic targets should thus be personalized and focus on both layer-to-layer interactions and early interventions.

Exercise stress echocardiogram for the evaluation of change in the ventricular-arterial interaction after thoracic endovascular aortic repair.

The aim of this study was to explore, with exercise echocardiography, the potential impact of thoracic endovascular aortic repair (TEVAR) on the ventricle-aorta coupling, based on the hypothesis that the interaction between the ventricle and aorta may be influenced by an increase in aortic stiffness due to the stent graft. Of the patients who underwent isolated TEVAR for thoracic aortic diseases between April 2016 and December 2016, changes found in haemodynamic and echocardiographic parameters between the control (n = 17) and TEVAR (n = 30) groups were analysed by a stress echocardiogram. The end-systolic elastance significantly increased with stress in both groups [from 3.0 (2.5-4.5) mmHg/ml to 4.8 (3.7-6.5) mmHg/ml, P < 0.001, in the control group and from 2.9 (2.0-3.5) mmHg/ml to 3.4 (2.6-4.2) mmHg/ml, P < 0.001, in the TEVAR group]. The arterial elastance significantly elevated only in the TEVAR group [from 1.6 (1.3-1.8) mmHg/ml to 1.7 (1.5-2.0) mmHg/ml, P = 0.007] and arterial elastance/end-systolic elastance (ventricular-arterial coupling) significantly decreased only in the control group [from 0.5 (0.4-0.7) to 0.4 (0.3-0.5), P = 0.002, in the control group and from 0.6 (0.4-0.8) to 0.5 (0.4-0.6), P = 0.10, in the TEVAR group]. In the control group, the change in end-systolic elastance and ventricular-arterial coupling tended to be greater (P = 0.002 and 0.07). An exercise echocardiogram showed the underlying influences of TEVAR on the interaction between the heart and aorta. TEVAR may have the potential to suppress left ventricular contractile capacity and increase cardiac afterload during exercise. A201770-01.

PO-286 The research about the evaluation index on cardiac reserve of female athletes

PO-286 The research about the evaluation index on cardiac reserve of female athletes