1,721,007 research outputs found
Intermediate filaments in the heart: The dynamic duo of desmin and lamins orchestrates mechanical force transmission
Full text linkThe intermediate filament (IF) cytoskeleton supports cellular structural integrity, particularly in response to mechanical stress. The most abundant IF proteins in mature cardiomyocytes are desmin and lamins. The desmin network tethers the contractile apparatus and organelles to the nuclear envelope and the sarcolemma, while lamins, as components of the nuclear lamina, provide structural stability to the nucleus and the genome. Mutations in desmin or A-type lamins typically result in cardiomyopathies and recent studies emphasized the synergistic roles of desmin and lamins in the maintenance of nuclear integrity in cardiac myocytes. Here we explore the emerging roles of the interdependent relationship between desmin and lamins in providing resilience to nuclear structure while transducing extracellular mechanical cues into the nucleus
New roles for desmin in the maintenance of muscle homeostasis
No full textDesmin is the primary intermediate filament (IF) of cardiac, skeletal, and smooth muscle. By linking the contractile myofibrils to the sarcolemma and cellular organelles, desmin IF contributes to muscle structural and cellular integrity, force transmission, and mitochondrial homeostasis. Mutations in desmin cause myofibril misalignment, mitochondrial dysfunction, and impaired mechanical integrity leading to cardiac and skeletal myopathies in humans, often characterized by the accumulation of protein aggregates. Recent evidence indicates that desmin filaments also regulate proteostasis and cell size. In skeletal muscle, changes in desmin filament dynamics can facilitate catabolic events as an adaptive response to a changing environment. In addition, post-translational modifications of desmin and its misfolding in the heart have emerged as key determinants of homeostasis and disease. In this review, we provide an overview of the structural and cellular roles of desmin and propose new models for its novel functions in preserving the homeostasis of striated muscles
Mechanisms of Cardiovascular Damage Induced by Traditional Chemotherapy
No full textTraditional chemotherapeutics are essential tools in the management of cancer patients. Nevertheless, these drugs are burdened by some degree of cardiovascular toxicity. Anthracycline-induced toxicity has been historically the most studied, but also the use of other drugs can be limited by a certain risk of cardiac and vascular toxicities. Here we acknowledge the main mechanistic insights, and we describe the different aspects of cardiotoxicity of these drugs, highlighting the different cellular compartments and cardiovascular components affected
Molecular Mechanisms of Cardiovascular Damage Induced by Anti-HER-2 Therapies
No full textIn the last two decades, newer biological drugs have been designed in order to “target” specific proteins involved in cancer proliferation and overcome the increased risk of cardiovascular toxicity associated with “broad-spectrum” classic chemotherapeutics. Unfortunately, these proteins are also important for the maintenance of cardiovascular homeostasis. The humanized anti-ErbB2 antibody, trastuzumab, is the prototypical biological drug first introduced in antineoplastic protocols for the treatment of ErbB2+ breast cancer. Indeed, not only is this protein overexpressed in several breast cancers, but also it plays a major role in the cardiovascular system in cell growth, including myocyte growth, and inhibition of apoptosis and can modulate the oxidative damage induced by anthracyclines. Hence, patients treated with trastuzumab developed systolic dysfunction, especially when administered with or shortly after doxorubicin
Pulmonary Hypertension Induced by Anticancer Drugs
No full textPulmonary vascular damage is a rare but possible complication of treatment with chemotherapeutic agents or bone marrow transplantation. The main clinical manifestations involving the pulmonary vessels are the development of pulmonary arterial hypertension or pulmonary veno-occlusive disease. In this chapter we describe the main mechanisms underlying the development of this form of toxicity, the screening algorithm, and its clinical management
Alternatives to Transplantation in the Treatment of Heart Failure: New Diagnostic and Therapeutic Insights
Full text linkThe aim of our current special issue was to present a series of original researches and reviews on recent advances in the diagnosis, medical therapy, and surgical approaches of heart failure.
As reported in the introductive review of Agnetti et al., cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndromes are leading to an increasing number of “survivors” who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be o ered only to a small percentage of patients who could bene t from a new heart due to the limited availability of donor organs. e authors reported in this comprehensive review the evaluation of the safety and e cacy of innovative approaches in the diagnosis and treatment of patients refrac- tory to standard medical therapy and excluded from cardiac transplantation lists
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Green tea modulation of inducible nitric oxide synthase in hypoxic/reoxygenated cardiomyocytes.
No full textHypoxia/reoxygenation (H/R) is one of the causes of the increased expression of inducible nitric oxide synthase (iNOS) in cardiomyocytes. Since an aberrant NOS induction has detrimental consequences, we evaluated the effect of a green tea extract (GTE) on the NOS induction and activity in H/R-cardiomyocytes to define a nutritional strategy. Cultured rat cardiomyocytes were exposed to H/R in the presence of two concentrations of a green tea extract (GTE), which is reported to inhibit NOS expression and activity in different cells. In cultured cardiomyocytes two NOS isoforms were constitutively expressed, but only iNOS was induced by H/R. GTE supplementation at the lowest concentration, comparable to that in human plasma after dietary consumption, was ineffective, while the highest, comparable to that achievable by dietary supplements, counteracted the effect of H/R on iNOS induction and activity. It is necessary to verify in humans the relationship between the modulation of NO production and green tea dietary consumption
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