Rationale: Atrial fibrillation (AF) and heart failure often coexist, but their interaction is poorly understood. Clinical data indicate that the arrhythmic component of AF may contribute to left ventricular (LV) dysfunction. Objective: This study investigates the effects and molecular mechanisms of AF on the human LV. Methods and Results: Ventricular myocardium from patients with aortic stenosis and preserved LV function with sinus rhythm or rate-controlled AF was studied. LV myocardium from patients with sinus rhythm and patients with AF showed no differences in fibrosis. In functional studies, systolic Ca ²⁺ transient amplitude of LV cardiomyocytes was reduced in patients with AF, while diastolic Ca ²⁺ levels and Ca ²⁺ transient kinetics were not statistically different. These results were confirmed in LV cardiomyocytes from nonfailing donors with sinus rhythm or AF. Moreover, normofrequent AF was simulated in vitro using arrhythmic or rhythmic pacing (both at 60 bpm). After 24 hours of AF-simulation, human LV cardiomyocytes from nonfailing donors showed an impaired Ca ²⁺ transient amplitude. For a standardized investigation of AF-simulation, human iPSC-cardiomyocytes were tested. Seven days of AF-simulation caused reduced systolic Ca ²⁺ transient amplitude and sarcoplasmic reticulum Ca ²⁺ load likely because of an increased diastolic sarcoplasmic reticulum Ca ²⁺ leak. Moreover, cytosolic Na ⁺ concentration was elevated and action potential duration was prolonged after AF-simulation. We detected an increased late Na ⁺ current as a potential trigger for the detrimentally altered Ca ²⁺ /Na ⁺ -interplay. Mechanistically, reactive oxygen species were higher in the LV of patients with AF. CaMKII (Ca ²⁺ /calmodulin-dependent protein kinase IIδc) was found to be more oxidized at Met281/282 in the LV of patients with AF leading to an increased CaMKII activity and consequent increased RyR2 phosphorylation. CaMKII inhibition and ROS scavenging ameliorated impaired systolic Ca ²⁺ handling after AF-simulation. Conclusions: AF causes distinct functional and molecular remodeling of the human LV. This translational study provides the first mechanistic characterization and the potential negative impact of AF in the absence of tachycardia on the human ventricle.

The understanding of macrophages and their pathophysiological role has dramatically changed within the last decades. Macrophages represent a very interesting cell type with regard to biomaterial-based tissue engineering and regeneration. In this context, macrophages play a crucial role in the biocompatibility and degradation of implanted biomaterials. Furthermore, a better understanding of the functionality of macrophages opens perspectives for potential guidance and modulation to turn inflammation into regeneration. Such knowledge may help to improve not only the biocompatibility of scaffold materials but also the integration, maturation, and preservation of scaffold-cell constructs or induce regeneration. Nowadays, macrophages are classified into two subpopulations, the classically activated macrophages (M1 macrophages) with pro-inflammatory properties and the alternatively activated macrophages (M2 macrophages) with anti-inflammatory properties. The present narrative review gives an overview of the different functions of macrophages and summarizes the recent state of knowledge regarding different types of macrophages and their functions, with special emphasis on tissue engineering and tissue regeneration.

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.

Objective: It is unclear whether and to what extent COVID-19 infection poses health risks and a chronic impairment of performance in athletes. Identification of individual health risk is an important decision-making basis for managing the pandemic risk of infection with SARS-CoV-2 in sports and return to play (RTP).Methods: This study aims 1) to analyze the longitudinal rate of seroprevalence of SARS-CoV-2 in German athletes, 2) to assess health-related consequences in athletes infected with SARS-CoV-2, and 3) to reveal effects of the COVID-19 pandemic in general and of a cleared SARS-CoV-2 infection on exercise performance. CoSmo-S is a prospective observational multicenter study establishing two cohorts: 1) athletes diagnosed positive for COVID-19 (cohort 1) and 2) federal squad athletes who perform their annual sports medical preparticipation screening (cohort 2). Comprehensive diagnostics including physical examination, laboratory blood analyses and blood biobanking, resting and exercise electrocardiogram (ECG), echocardiography, spirometry and exercise testing added by questionnaires are conducted at baseline and follow-up.Results and Conclusion: We expect that the results obtained, will allow us to formulate recommendations regarding RTP on a more evidence-based level.

Cilia are cellular organelles that project from the cell. They occur in nearly all non-hematopoietic tissues and have different functions in different tissues. In mesenchymal tissues primary cilia play a crucial role in the adequate morphogenesis during embryological development. In mature articular cartilage, primary cilia fulfil chemo- and mechanosensitive functions to adapt the cellular mechanisms on extracellular changes and thus, maintain tissue homeostasis and morphometry. Ciliary abnormalities in osteoarthritic cartilage could represent pathophysiological relationships between ciliary dysfunction and tissue deformation. Nevertheless, the molecular and pathophysiological relationships of ‘Primary Cilia’ (PC) in the context of osteoarthritis is not yet fully understood. The present review focuses on the current knowledge about PC and provide a short but not exhaustive overview of their role in cartilage.