Viral myocarditis in combination with genetic cardiomyopathy as a cause of sudden death. An autopsy series.

Sudden cardiac death (SCD) is a major public health issue worldwide. In the young (< 40 years of age), genetic cardiomyopathies and viral myocarditis, sometimes in combination, are the most frequent, but underestimated, causes of SCD. Molecular autopsy is essential for prevention.

Generation of human induced pluripotent stem cell lines from five patients with Myofibrillar myopathy carrying different heterozygous mutations in the DES gene.

Myofibrillar myopathy (MFM) is a rare genetic disorder characterized by muscular dystrophy that is often associated with cardiac disease. This disease is caused by mutations in several genes, among them DES (encoding desmin) is the most frequently affected. Peripheral blood mononuclear cells from 5 different MFM patients with different DES mutations were reprogrammed into induced pluripotent stem cells (IPSC) using non-integrative vectors.

Undernutrition in young children with congenital heart disease undergoing cardiac surgery in a low-income environment.

Background: Malnutrition (undernutrition) in children with congenital disease (CHD) is a notable concern, with preoperative and persistent growth failure post-cardiac surgery contributing to poorer outcomes. Poor growth in children with CHD in low-income environments is exacerbated by feeding difficulties, poverty, delayed diagnosis, and late corrective surgery. This study describes and compares the growth of young children with CHD undergoing cardiac surgery in central South Africa from before to 6-months after cardiac surgery.

Critical contribution of mitochondria in the development of cardiomyopathy linked to desmin mutation.

Background: Beyond the observed alterations in cellular structure and mitochondria, the mechanisms linking rare genetic mutations to the development of heart failure in patients affected by desmin mutations remain unclear due in part, to the lack of relevant human cardiomyocyte models.

Methods: To shed light on the role of mitochondria in these mechanisms, we investigated cardiomyocytes derived from human induced pluripotent stem cells carrying the heterozygous DES mutation that were either isolated from a patient or generated by gene editing. To increase physiological relevance, cardiomyocytes were either cultured on an anisotropic micropatterned surface to obtain elongated and aligned cardiomyocytes, or as a cardiac spheroid to create a micro-tissue.

Generation of induced pluripotent stem cell line (TMOi001-A-11) carrying a homozygous deletion in the synemin gene using CRISPR/Cas9.

A number of genetic variants in the SYNM gene encoding for the intermediate filament synemin have been reported in patients with cardiomyopathies, skeletal myopathies, cancer and certain neurodegenerative disorders. To better understand its role, we generated a human induced pluripotent stem cell line with a homozygous deletion in the SYNM gene by CRISPR/Cas9 genome editing. The synemin-knockout human induced pluripotent stem cells exhibit typical morphology of pluripotent cells, expression of pluripotency markers, normal karyotype and differentiation capacity in the three germ layers.

Anisotropic dense collagen hydrogels with two ranges of porosity to mimic the skeletal muscle extracellular matrix.

Despite the crucial role of the extracellular matrix (ECM) in the organotypic organization and function of skeletal muscles, most 3D models do not mimic its specific characteristics, namely its biochemical composition, stiffness, anisotropy, and porosity. Here, a novel 3D in vitro model of muscle ECM was developed reproducing these four crucial characteristics of the native ECM. An anisotropic hydrogel mimicking the muscle fascia was obtained thanks to unidirectional 3D printing of dense collagen with aligned collagen fibrils.

Generation of an Adequate Perfusion Network within Dense Collagen Hydrogels Using Thermoplastic Polymers as Sacrificial Matrix to Promote Cell Viability.

Dense collagen hydrogels are promising biomaterials for several tissue-engineering applications. They exhibit high mechanical properties, similar to physiological extracellular matrices, and do not shrink under cellular activity. However, they suffer from several drawbacks, such as weak nutrient and O diffusion, impacting cell survival.

Desmin Modulates Muscle Cell Adhesion and Migration.

Cellular adhesion and migration are key functions that are disrupted in numerous diseases. We report that desmin, a type-III muscle-specific intermediate filament, is a novel cell adhesion regulator. Expression of p.

3D models of dilated cardiomyopathy: Shaping the chemical, physical and topographical properties of biomaterials to mimic the cardiac extracellular matrix.

The pathophysiology of dilated cardiomyopathy (DCM), one major cause of heart failure, is characterized by the dilation of the heart but remains poorly understood because of the lack of adequate models. Current 2D models do not allow for the 3D organotypic organization of cardiomyocytes and do not reproduce the ECM perturbations. In this review, the different strategies to mimic the chemical, physical and topographical properties of the cardiac tissue affected by DCM are presented.

Absence of Desmin Results in Impaired Adaptive Response to Mechanical Overloading of Skeletal Muscle.

Desmin is a muscle-specific protein belonging to the intermediate filament family. Desmin mutations are linked to skeletal muscle defects, including inherited myopathies with severe clinical manifestations. The aim of this study was to examine the role of desmin in skeletal muscle remodeling and performance gain induced by muscle mechanical overloading which mimics resistance training.

Impaired Binding to Junctophilin-2 and Nanostructural Alteration in CPVT Mutation.

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Polyacrylamide Hydrogels with Rigidity-Independent Surface Chemistry Show Limited Long-Term Maintenance of Pluripotency of Human Induced Pluripotent Stem Cells on Soft Substrates.

In general, cells are cultured and adapted to the in vitro rigidities of plastic or glass ranging between 1 and 10 GPa, which is very far from physiological values that are mostly in the kilopascal range. Stem cells however show a high sensitivity to the rigidity of their culture environment, which impacts their differentiation program. Here, we address the impact of rigidity on the long-term maintenance of pluripotency in human induced pluripotent stem cells (hiPSCs) to determine whether soft substrates could provide a new standard for hiPSC expansion and maintenance.

Aldehyde dehydrogenases contribute to skeletal muscle homeostasis in healthy, aging, and Duchenne muscular dystrophy patients.

Background: Aldehyde dehydrogenases (ALDHs) are key players in cell survival, protection, and differentiation via the metabolism and detoxification of aldehydes. ALDH activity is also a marker of stem cells. The skeletal muscle contains populations of ALDH-positive cells amenable to use in cell therapy, whose distribution, persistence in aging, and modifications in myopathic context have not been investigated yet.

Nanofibrous clinical-grade collagen scaffolds seeded with human cardiomyocytes induces cardiac remodeling in dilated cardiomyopathy.

Limited data are available on the effects of stem cells in non-ischemic dilated cardiomyopathy (DCM). Since the diffuse nature of the disease calls for a broad distribution of cells, this study investigated the scaffold-based delivery of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) in a mouse model of DCM. Nanofibrous scaffolds were produced using a clinical grade atelocollagen which was electrospun and cross-linked under different conditions.

Mechanical Overloading Increases Maximal Force and Reduces Fragility in Hind Limb Skeletal Muscle from Mdx Mouse.

There is fear that mechanical overloading (OVL; ie, high-force contractions) accelerates Duchenne muscular dystrophy. Herein, we determined whether short-term OVL combined with wheel running, short-term OVL combined with irradiation, and long-term OVL are detrimental for hind limb mdx mouse muscle, a murine model of Duchene muscular dystrophy exhibiting milder dystrophic features. OVL was induced by the surgical ablation of the synergic muscles of the plantaris muscle, a fast muscle susceptible to contraction-induced muscle damage in mdx mice.

Effect of voluntary physical activity initiated at age 7 months on skeletal hindlimb and cardiac muscle function in mdx mice of both genders.

Introduction: The effects of voluntary activity initiated in adult mdx (C57BL/10ScSc-DMD(mdx) /J) mice on skeletal and cardiac muscle function have not been studied extensively.

Methods: We studied the effects of 3 months of voluntary wheel running initiated at age 7 months on hindlimb muscle weakness, increased susceptibility to muscle contraction-induced injury, and left ventricular function in mdx mice.

Results: We found that voluntary wheel running did not worsen the deficit in force-generating capacity and the force drop after lengthening contractions in either mdx mouse gender.

Long-term functional benefits of human embryonic stem cell-derived cardiac progenitors embedded into a fibrin scaffold.

Background: Cardiac-committed cells and biomimetic scaffolds independently improve the therapeutic efficacy of stem cells. In this study we tested the long-term effects of their combination.

Methods: Eighty immune-deficient rats underwent permanent coronary artery ligation.

Investigating the role of GXXXG motifs in helical folding and self-association of plasticins, Gly/Leu-rich antimicrobial peptides.

Plasticins (PTC) are dermaseptin-related antimicrobial peptides characterized by a large number of leucine and glycine residues arranged in GXXXG motifs that are often described to promote helix association within biological membranes. We report the structure and interaction properties of two plasticins, PTC-B1 from Phyllomedusa bicolor and a cationic analog of PTC-DA1 from Pachymedusa dacnicolor, which exhibit membrane-lytic activities on a broad range of microorganisms. Despite a high number of glycine, CD and NMR spectroscopy show that the two plasticins adopt mainly alpha-helical conformations in a wide variety of environments such as trifluoroethanol, detergent micelles and lipid vesicles.

Myofiber androgen receptor promotes maximal mechanical overload-induced muscle hypertrophy and fiber type transition in male mice.

The first aim of this study was to examine the role of myofiber androgen receptor (AR) in male mice on muscle performance gain and remodeling-induced muscle mechanical overloading (OVL) that mimics resistance training. The response of OVL in mice in which AR is selectively ablated in myofibers (AR(skm-/y)) was compared with that of wild-type (WT) mice. In addition, we determined whether the synthetic anabolic androgen nandrolone administration affects the OVL response.

Synemin acts as a regulator of signalling molecules during skeletal muscle hypertrophy.

Synemin, a type IV intermediate filament (IF) protein, forms a bridge between IFs and cellular membranes. As an A-kinase-anchoring protein, it also provides temporal and spatial targeting of protein kinase A (PKA). However, little is known about its functional roles in either process.

Advances in the understanding of skeletal muscle weakness in murine models of diseases affecting nerve-evoked muscle activity, motor neurons, synapses and myofibers.

Disease processes and trauma affecting nerve-evoked muscle activity, motor neurons, synapses and myofibers cause different levels of muscle weakness, i.e., reduced maximal force production in response to voluntary activation or nerve stimulation.

Efficacy of epicardially delivered adipose stroma cell sheets in dilated cardiomyopathy.

Aims: Few studies have assessed the effects of cell therapy in non-ischaemic cardiomyopathies which, however, contribute to a large number of cardiac failures. Assuming that such conditions are best suited for a global delivery of cells, we assessed the effects of epicardially delivered adipose tissue-derived stroma cell (ADSC) sheets in a mouse model of dilated cardiomyopathy based on cardiac-specific and tamoxifen-inducible invalidation of serum response factor.

Methods And Results: Three weeks after tamoxifen administration, the function of the left ventricle (LV) was assessed by echocardiography.

Protective effect of female gender-related factors on muscle force-generating capacity and fragility in the dystrophic mdx mouse.

Introduction: The dystrophic features in hindlimb skeletal muscles of female mdx mice are unclear.

Methods: We analyzed force-generating capacity and force decline after lengthening contraction-induced damage (fragility).

Results: Young (6-month-old) female mdx mice displayed reduced force-generating capacity (-18%) and higher fragility (23% force decline) compared with female age-matched wild-type mice.

Voluntary physical activity protects from susceptibility to skeletal muscle contraction-induced injury but worsens heart function in mdx mice.

It is well known that inactivity/activity influences skeletal muscle physiological characteristics. However, the effects of inactivity/activity on muscle weakness and increased susceptibility to muscle contraction-induced injury have not been extensively studied in mdx mice, a murine model of Duchenne muscular dystrophy with dystrophin deficiency. In the present study, we demonstrate that inactivity (ie, leg immobilization) worsened the muscle weakness and the susceptibility to contraction-induced injury in mdx mice.