Contractile Character Research Articles

In vitro effect of leptin on human cardiac contractility.

Leptin, a hormone produced by adipose tissue, has been linked to many regulatory pathways. Its role in the complex relationship between obesity and CVD is not yet clear. The aim of the present study was to evaluate whether leptin interferes directly with cardiac function regulation, altering its contractile force character, and hence contributing to different pathological processes. Muscle samples were obtained from human atrial myocardium. Each trial included two samples from the same patient. They were simultaneously electrically stimulated under sustained perfusion to perform isometric contractions. One sample was treated with a high concentration of human recombinant leptin (1 µg/ml). The other was treated with placebo and served as a control. The exhibited contraction forces (CF) and the contraction duration (CD) after 20 min of treatment were normalised by dividing them by the values before the treatment and reported as a percentage. A total of ten successful trials were conducted. Exposure to leptin did not yield a statistically significant variation in both CF and CF. In the treatment group, CF% measured 108 (95% CI 91, 125)% and CD% measured 95 (95% CI 90, 101)% after 20 min. In the control group, CF% measured 105 (90% CI 84, 126)% and CD% measured 92 (95% CI 80, 105)% after 20 min. We concluded that leptin does not alter the contractile character of human atrial tissues, even in supraphysiological dosage. These results suggest that leptin does not play a role in short-term cardiac regulation.

Atherosclerosis-associated differentially methylated regions can reflect the disease phenotype and are often at enhancers

Background and aimsAtherosclerosis is a widespread and complicated disease involving phenotypic modulation and transdifferentiation of vascular smooth muscle cells (SMCs), the predominant cells in aorta, as well as changes in endothelial cells and infiltrating monocytes. Alterations in DNA methylation are likely to play central roles in these phenotypic changes, just as they do in normal differentiation and cancer. MethodsWe examined genome-wide DNA methylation changes in atherosclerotic aorta using more stringent criteria for differentially methylated regions (DMRs) than in previous studies and compared these DMRs to tissue-specific epigenetic features. ResultsWe found that disease-linked hypermethylated DMRs account for 85% of the total atherosclerosis-associated DMRs and often overlap aorta-associated enhancer chromatin. These hypermethylated DMRs were associated with functionally different sets of genes compared to atherosclerosis-linked hypomethylated DMRs. The extent and nature of the DMRs could not be explained as direct effects of monocyte/macrophage infiltration. Among the known atherosclerosis- and contractile SMC-related genes that exhibited hypermethylated DMRs at aorta enhancer chromatin were ACTA2 (aorta α2 smooth muscle actin), ELN (elastin), MYOCD (myocardin), C9orf3 (miR-23b and miR-27b host gene), and MYH11 (smooth muscle myosin). Our analyses also suggest a role in atherosclerosis for developmental transcription factor genes having little or no previous association with atherosclerosis, such as NR2F2 (COUP-TFII) and TBX18. ConclusionsWe provide evidence for atherosclerosis-linked DNA methylation changes in aorta SMCs that might help minimize or reverse the standard contractile character of many of these cells by down-modulating aorta SMC-related enhancers, thereby facilitating pro-atherosclerotic phenotypic changes in many SMCs.

Erratum to: Identification of functional differences between recombinant human α and β cardiac myosin motors.

The myosin isoform composition of the heart is dynamic in health and disease and has been shown to affect contractile velocity and force generation. While different mammalian species express different proportions of α and β myosin heavy chain, healthy human heart ventricles express these isoforms in a ratio of about 1:9 (α:β) while failing human ventricles express no detectable α-myosin. We report here fast-kinetic analysis of recombinant human α and β myosin heavy chain motor domains. This represents the first such analysis of any human muscle myosin motor and the first of α-myosin from any species. Our findings reveal substantial isoform differences in individual kinetic parameters, overall contractile character, and predicted cycle times. For these parameters, α-subfragment 1 (S1) is far more similar to adult fast skeletal muscle myosin isoforms than to the slow β isoform despite 91% sequence identity between the motor domains of α- and β-myosin. Among the features that differentiate α- from β-S1: the ATP hydrolysis step of α-S1 is ~ten-fold faster than β-S1, α-S1 exhibits ~five-fold weaker actin affinity than β-S1, and actin·α-S1 exhibits rapid ADP release, which is >ten-fold faster than ADP release for β-S1. Overall, the cycle times are ten-fold faster for α-S1 but the portion of time each myosin spends tightly bound to actin (the duty ratio) is similar. Sequence analysis points to regions that might underlie the basis for this finding.

Functional characterization of human coronary artery smooth muscle cells under cyclic mechanical strain in a degradable polyurethane scaffold

There are few synthetic elastomeric biomaterials that simultaneously provide the required biological conditioning and the ability to translate biomechanical stimuli to vascular smooth muscle cells (VSMCs). Biomechanical stresses are important physiological elements that regulate VSMC function, and polyurethane elastomers are a class of materials capable of facilitating the translation of stress induced biomechanics. In this study, human coronary artery smooth muscle cells (hCASMCs), which were seeded into a porous degradable polar/hydrophobic/ionic (D-PHI) polyurethane scaffold, were subjected to uniaxial cyclic mechanical strain (CMS) over a span of four weeks using a customized bioreactor. The distribution, proliferation and contractile protein expression of hCASMCs in the scaffold were then analyzed and compared to those grown under static conditions. Four weeks of CMS, applied to the elastomeric scaffold, resulted in statistically greater DNA mass, more cell area coverage and a better distribution of cells deeper within the scaffold construct. Furthermore, CMS samples demonstrated improved tensile mechanical properties following four weeks of culture, suggesting the generation of more extracellular matrix within the polyurethane constructs. The expression of smooth muscle α-actin, calponin and smooth muscle myosin heavy chain and the absence of Ki-67+ cells in both static and CMS cultures, throughout the 4 weeks, suggest that hCASMCs retained their contractile character on these biomaterials. The study highlights the importance of implementing physiologically-relevant biomechanical stimuli in the development of synthetic elastomeric tissue engineering scaffolds.

Muscle afferent contributions to the cardiovascular response to isometric exercise.

The cardiovascular response to isometric exercise is governed by both central and peripheral mechanisms. Both metabolic and mechanical stresses on the exercising skeletal muscle produce cardiovascular change, yet it is often overlooked that the afferent signal arising from the muscle can be modified by factors other than exercise intensity. This review discusses research revealing that muscle fibre type, muscle mass and training status are important factors in modifying this peripheral feedback from the active muscles. Studies in both animals and humans have shown that the pressor response resulting from exercise of muscle with a faster contractile character and isomyosin content is greater than that from a muscle of slower contractile character. Athletic groups participating in training programmes that place a high anaerobic load on skeletal muscle groups show attenuated muscle afferent feedback. Similarly, longitudinal studies have shown that specific local muscle training also blunts the pressor response to isometric exercise. Thus it appears that training may decrease the metabolic stimulation of muscle afferents and in some instances chronic exposure to the products of anaerobic metabolism may blunt the sensitivity of the muscle metaboreflex. There may be surprising parallels between the local muscle conditions induced in athletes training for longer sprint events (e.g. 400 m) and by the low-flow conditions in, for example, the muscles of chronic heart failure patients. Whether their similar attenuations in muscle afferent feedback during exercise are due to decreased metabolite accumulation or to a desensitization of the muscle afferents is not yet known.

Sarcoplasmic reticulum function and muscle contractile character following fatiguing exercise in humans.

1. This study examined the alterations in calcium release, calcium uptake and calcium ATPase activity of skeletal muscle sarcoplasmic reticulum in response to a bout of intense dynamic knee extensor exercise, and the relationship between these changes and alterations in muscle contractile characteristics in the human quadriceps. 2. In biopsy samples taken from the vastus lateralis, sarcoplasmic reticulum calcium release and calcium uptake were significantly depressed (P < 0.01 and 0.05, respectively) immediately following the exercise with no alteration in the sarcoplasmic reticulum Ca2+-ATPase activity. 3. A 33 % reduction in the maximum voluntary isometric torque was found following the exercise, with reduced torques from electrically evoked isometric contractions at low frequencies of stimulation (10 and 20 Hz) but not at higher frequencies (50 and 100 Hz). 4. The depressed calcium release was correlated (P < 0.05) with a decreased ratio of torques generated at 20:50 Hz, indicating an involvement in low frequency fatigue; however, no correlations between the muscle relaxation times or rates of change of torque and calcium uptake were observed.

Invagination operation for esophageal diverticulum

1. 1. The author has attempted to review briefly the salient features of esophageal diverticula. 2. 2. Case reports are hereby given illustrating a method for inversion of the sac and repair of the orifice. 3. 3. This operation is recommended by the author because: (1) It allows the patient to be operated on at one stage; (2) the sac is not opened so that the danger of infection is minimized; (3) the natural contractile character of the sac causes it to shrink and causes no trouble by its presence in the pharynx; (4) it adds another method of operating which may be used to advantage in selected cases, and (5) our patients have had very satisfactory results and continue to enjoy perfect health. The author, therefore, recommends this procedure.

Invagination operation for esophageal diverticula

1. 1. The author has attempted to review briefly the salient features of esophageal diverticula. 2. 2. A case report is hereby given illustrating a method for inversion of the sac and repair of the orifice. 3. 3. This operation is recommended by the author because: 3.1. a. It allows the patient to be operated on at one stage. 3.2. b. The sac is not opened so that the danger of infection is minimized. 3.3. c. The natural contractile character of the sac causes it to shrink and causes no trouble by its presence in the pharynx. 3.4. d. It adds another method of operating which may be used to advantage in selected cases. 3.5. e. The patient in this instance has had a very satisfactory result and continues to enjoy perfect health. The author therefore recommends this procedure in selected cases.