Heart muscle contraction

Coronary artery spasm (CAS) plays an important role in the pathogeneses of various ischemic heart diseases and has gradually become a common cause of life-threatening arrhythmia. The specific molecular mechanism of CAS has not been fully elucidated, nor are there any specific diagnostic markers for the condition. Therefore, this study aimed to examine the specific molecular mechanism underlying CAS, and screen for potential diagnostic markers. To this end, we successfully constructed a rat CAS model and achieved in vitro culture of a human coronary-artery smooth-muscle cell (hCASMC) contraction model...

Advanced in vitro models that recapitulate the structural organization and function of the human heart are highly needed for accurate disease modeling, more predictable drug screening and safety pharmacology. Conventional 3D Engineered Heart Tissues (EHTs) lack heterotypic cell complexity and culture under flow, whereas microfluidic Heart-on-Chip (HoC) models in general lack the 3D configuration and accurate contractile readouts. In this study, an innovative and user-friendly HoC model is developed to overcome these limitations, by culturing human pluripotent stem cell (hPSC)-derived cardiomyocytes, endothelial- and smooth muscle cells, together with human cardiac fibroblasts, under flow, leading to self-organized miniaturized micro-EHTs (μEHTs) with a cardiomyocyte-endothelial cell interface reminiscent of the physiological capillary lining...

Caffeine is the most widely consumed psychoactive substance worldwide, affecting numerous tissues and organs, with notable impacts on the central nervous system, heart, and blood vessels. The effect of caffeine on vascular smooth muscle cells is an initial transient contraction followed by significant vasodilatation. In this study we investigate the use of diffuse reflectance spectroscopy (DRS) for monitoring of vascular changes in human skin induced by caffeine consumption. DRS spectra were recorded on volar sides of the forearms of eight healthy volunteers at time intervals of 0, 30, 60, 120, and 180 min after consumption of caffeine, while one subject served as a negative control...

New or mild heart failure (HF) is mainly caused by left ventricular dysfunction. We hypothesised that gene expression differ between the left (LV) and right ventricle (RV) and secondly by type of LV dysfunction. We compared gene expression through myocardial biopsies from LV and RV of patients undergoing elective coronary bypass surgery (CABG). Patients were categorised based on LV ejection fraction (EF), diastolic function and NT-proBNP into pEF (preserved; LVEF ≥ 45%), rEF (reduced; LVEF < 45%) or normal LV function...

Many organs are designed to move: the heart pumps each second, the gastrointestinal tract squeezes and churns to digest food, and we contract and relax skeletal muscles to move our bodies. Sensory neurons of the peripheral nervous system detect signals from bodily tissues, including the forces generated by these movements, to control physiology. The processing of these internal signals is called interoception, but this is a broad term that includes a wide variety of both chemical and mechanical sensory processes...

This study compared the effect of continuous low-intensity aerobic exercise with blood flow restriction (LI-AE-BFR) versus high-intensity interval exercise (HIIE), matching total external mechanical work between conditions, on perceptual (exertion, pain, affective and pleasure) and physiological responses (heart rate [HR], blood lactate [BL] and muscle fatigue). Ten healthy untrained men (25.6 ± 3.78 years old; 75.02 ± 12.02 kg; 172.2 ± 6.76 cm; 24.95 ± 3.16 kg/m²) completed three visits to the laboratory...

The emergence of mechanobiology has unveiled complex mechanisms by which cells adjust intracellular force production to their needs. Most communicable intracellular forces are generated by myosin II, an actin-associated molecular motor that transforms adenosine triphosphate (ATP) hydrolysis into contraction in nonmuscle and muscle cells. Myosin II-dependent force generation is tightly regulated, and deregulation is associated with specific pathologies. Here, we focus on the role of myosin II (nonmuscle myosin II, NMII) in force generation and mechanobiology...

Cardiotoxicity induced by anti-cancer drugs is a significant concern for patients undergoing cancer treatment. Some anti-cancer drugs can damage cardiac muscle cells directly or indirectly, potentially leading to severe heart failure. Various risk factors, including the type and dosage of chemotherapy agents as well as patient background, contribute to the development of cardiotoxicity. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), which enable patient-specific toxicity prediction, hold great promise in this regard...

Native top-down mass spectrometry (nTDMS) has emerged as a powerful structural biology tool that can localize post-translational modifications (PTMs), explore ligand-binding interactions, and elucidate the three-dimensional structure of proteins and protein complexes in the gas-phase. Fourier-transform ion cyclotron resonance (FTICR) MS offers distinct capabilities for nTDMS, owing to its ultrahigh resolving power, mass accuracy, and robust fragmentation techniques. Previous nTDMS studies using FTICR have mainly been applied to overexpressed recombinant proteins and protein complexes...

Dermatomyositis, an autoimmune inflammatory myositis commonly linked to polymyositis, is marked by inflammatory and degenerative transformations impacting muscles, skin, limb girdles, the neck, and the pharynx. These changes result in symmetrical weakness and diverse levels of muscle atrophy. Uncommonly, the condition may impact the esophagus, lungs, and heart. While dermatomyositis is believed to involve genetic, immunological, and environmental factors, its precise etiology remains elusive. Typically, the classical presentation involves a symmetrical proximal myopathy alongside dermatological manifestations such as a purplish-red rash affecting the face, arms, hands, legs, and other areas...

BACKGROUND: A nonvolitional diagnostic method based on FES-Cycling technology has recently been demonstrated for mechanically ventilated patients. This method presents good sensitivity and specificity for detecting muscle dysfunction and survival prognosis, even in unconscious patients. As the clinical relevance of this method has already been reported, we aimed to evaluate its safety and feasibility. METHODS: An observational prospective study was carried out with 20 critically ill, mechanically ventilated patients...

It is well known that in the heart and kidney mitochondria, more than 95% of ATP production is supported by the β-oxidation of long-chain fatty acids. However, the β-oxidation of fatty acids by mitochondria has been studied much less than the substrates formed during the catabolism of carbohydrates and amino acids. In the last few decades, several discoveries have been made that are directly related to fatty acid oxidation. In this review, we made an attempt to re-evaluate the β-oxidation of long-chain fatty acids from the perspectives of new discoveries...

Phospholipases A2 (PLA2 s) are a large family of snake toxins manifesting diverse biological effects, which are not always related to phospholipolytic activity. Snake venom PLA2 s (svPLA2 s) are extracellular proteins with a molecular mass of 13-14 kDa. They are present in venoms in the form of monomers, dimers, and larger oligomers. The cardiovascular system is one of the multiple svPLA2 targets in prey organisms. The results obtained previously on the cardiovascular effects of monomeric svPLA2 s were inconsistent, while the data on the dimeric svPLA2 crotoxin from the rattlesnake Crotalus durissus terrificus showed that it significantly reduced the contractile force of guinea pig hearts...

OBJECTIVE: The objective of this article is to evaluate near-infrared spectroscopy (NIRS), a non-invasive technique to assess tissue oxygenation and mitochondrial function, as a diagnostic tool for statin-associated muscle symptoms (SAMS). METHODS: We verified SAMS in 39 statin-treated patients (23 women) using a double-blind, placebo-controlled, cross-over protocol. Subjects with suspected SAMS were randomised to simvastatin 20 mg/day or placebo for 8 weeks, followed by a 4-week no treatment period and then assigned to the alternative treatment, either simvastatin or placebo...

Heart muscle has the unique property that it can never rest; all cardiomyocytes contract with each heartbeat which requires a complex control mechanism to regulate cardiac output to physiological requirements. Changes in calcium concentration regulate the thin filament activation. A separate but linked mechanism regulates the thick filament activation, which frees sufficient myosin heads to bind the thin filament, thereby producing the required force. Thick filaments contain additional nonmyosin proteins, myosin-binding protein C and titin, the latter being the protein that transmits applied tension to the thick filament...

GPCR-Gi protein pathways are involved in the regulation of vagus muscarinic pathway under physiological conditions and are closely associated with the regulation of internal visceral organs. The muscarinic receptor-operated cationic channel is important in GPCR-Gi protein signal transduction as it decreases heart rate and increases GI rhythm frequency. In the SA node of the heart, acetylcholine binds to the M2 receptor and the released Gβγ activates GIRK (I(K,ACh)) channel, inducing a negative chronotropic action...

Of the ions involved in myocardial function, Ca2+ is the most important. Ca2+ is crucial to the process that allows myocardium to repeatedly contract and relax in a well-organized fashion; it is the process called excitation-contraction coupling. In order, therefore, for accurate comprehension of the physiology of the heart, it is fundamentally important to understand the detailed mechanism by which the intracellular Ca2+ concentration is regulated to elicit excitation-contraction coupling. Aequorin was discovered by Shimomura, Johnson and Saiga in 1962...

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently consumed by athletes to manage muscle soreness, expedite recovery, or improve performance. Despite the prevalence of NSAID use, their effects on muscle soreness and performance, particularly when administered prophylactically, remain unclear. This randomized, double-blind, counter-balanced, crossover study examined the effect of consuming a single dose of each of three NSAIDs (celecoxib, 200 mg; ibuprofen, 800 mg; flurbiprofen, 100 mg) or placebo 2 h before on muscle soreness and performance following an acute plyometric training session...

Cardiac dysfunction frequently emerges in the initial stages of cancer cachexia, posing a significant complication of the disease. Physical fitness is commonly recommended in these early stages of cancer cachexia due to its beneficial impacts on various aspects of the condition, including cardiac dysfunction. However, the direct functional impacts of exercise on the heart during cancer cachexia largely remain unexplored. In this study, we induced cancer cachexia in mice using a metastatic B16F10 melanoma model...

Cardiac contractility modulation (CCM) is based on electrical stimulation of the heart without alteration of action potential and mechanical activation, the data on its fundamental molecular mechanisms are limited. Here we demonstrate clinical and physiological effect of 12 months CCM in 29 patients along with transcriptomic molecular data. Based on the CCM effect the patients were divided into two groups: responders ( n  = 13) and non-responders ( n  = 16). RNA-seq data were collected for 6 patients before and after CCM including 3 responders and 3 non-responders...