Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot located between the myocardium and the visceral pericardium, exerting direct paracrine and vasocrine effects on the heart and coronary vessels. Under physiological conditions, EAT supports myocardial energy metabolism and thermoregulation through fatty acid supply and adaptive metabolic flexibility. In cardiometabolic disorders such as obesity, type 2 diabetes, and heart failure, EAT undergoes pathological remodelling characterized by increased thickness, adipocyte hypertrophy, immune cell infiltration, and secretion of pro‐inflammatory and fibrotic mediators. These alterations contribute to myocardial fibrosis, stiffness, and coronary atherosclerosis, particularly in heart failure with preserved ejection fraction. Pharmacological modulation of EAT has therefore emerged as a promising therapeutic approach in cardiovascular prevention. Agents such as statins, peroxisome proliferator‐activated receptor gamma agonists, adenosine monophosphate–activated protein kinase activators, glucagon‐like peptide‐1 receptor agonists, and sodium‐glucose cotransporter 2 inhibitors exert both systemic and depot‐specific effects. They reduce EAT thickness, suppress inflammatory signalling, enhance insulin sensitivity, and promote adipocyte browning and oxidative metabolism. Among these, sodium‐glucose cotransporter 2 inhibitors and glucagon‐like peptide‐1 receptor agonists show the most consistent effects in shifting EAT towards a less inflammatory and more metabolically active phenotype. The goal of this review is to provide an overview of current pharmacological interventions that influence EAT and to summarize how much is known about their molecular mechanisms from in vitro and in vivo studies. The target audience includes cardiovascular researchers and clinicians seeking to better understand how metabolic and antidiabetic therapies modulate cardiac fat biology and function.

Elevated levels of saturated very long-chain fatty acids (VLCFAs) in cell membranes and secreted lipoparticles have been associated with neurotoxicity and, therefore, require tight regulation. Excessive VLCFAs are imported into peroxisomes for degradation by β-oxidation. Impaired VLCFA catabolism due to primary or secondary peroxisomal alterations is featured in neurodegenerative and neuroinflammatory disorders such as X-linked adrenoleukodystrophy and multiple sclerosis (MS). Here, we identified that healthy human macrophages upregulate the peroxisomal genes involved in β-oxidation during myelin phagocytosis and pro-inflammatory activation, and that this response is impaired in peripheral macrophages and phagocytes in brain white matter lesions in MS patients. The pharmacological targeting of VLCFA metabolism and peroxisomes in innate immune cells could be favorable in the context of neuroinflammation and neurodegeneration. We previously identified the epigenetic histone deacetylase (HDAC) inhibitors entinostat and vorinostat to enhance VLCFA degradation and pro-regenerative macrophage polarization. However, adverse side effects currently limit their use in chronic neuroinflammation. Here, we focused on tefinostat, a monocyte/macrophage-selective HDAC inhibitor that has shown reduced toxicity in clinical trials. By using a gene expression analysis, peroxisomal β-oxidation assay, and live imaging of primary human macrophages, we assessed the efficacy of tefinostat in modulating VLCFA metabolism, phagocytosis, chemotaxis, and immune function. Our results revealed the significant stimulation of VLCFA degradation with the upregulation of genes involved in peroxisomal β-oxidation and interference with immune cell recruitment; however, tefinostat was less potent than the class I HDAC-selective inhibitor entinostat in promoting a regenerative macrophage phenotype. Further research is needed to fully explore the potential of class I HDAC inhibition and downstream targets in the context of neuroinflammation.

Adipose tissue enlargement in obesity leads to hypoxia, which may promote premature aging. This study aimed to understand the hypoxic response in 3D cultures of SGBS cells, a model for brown-like adipose tissue expressing uncoupling protein 1 (UCP1). Single-nucleus RNA sequencing of SGBS organoids revealed a heterogeneous composition and sub-population-specific responses to hypoxia. The analysis identified a cluster of transcriptional repression, indicating dying cells, and implied a role of ferroptosis in this model. Further experiments with SGBS cells and white adipose tissue-derived stem/progenitor cells showed that Acyl-CoA synthetase long-chain family member 4 (ACSL4), a key enzyme in ferroptosis, is expressed only in the presence of browning factors. Hypoxia downregulated ACSL4 protein in SGBS organoids but induced an inflammaging phenotype. Analysis of brown-like epicardial adipose tissue from cardiac surgery patients revealed a significant positive correlation of ACSL4 mRNA with UCP1 and hypoxia-inducible pro-inflammatory markers, while ACSL4 protein appeared to be inversely correlated. In conclusion, this study demonstrates that adipocytes’ capability to undergo ACSL4-mediated ferroptosis is linked to brown-like adipogenesis, suggesting an opportunity to modulate ferroptotic signaling in adipose tissue. The dual role of hypoxia by inhibiting ACSL4 but promoting inflammaging indicates a relationship between ferroptosis and aging that warrants further investigation.

Advanced Therapeutic Medicinal Products (ATMPs) eröffnen neue Therapieperspektiven, stoßen jedoch in der Praxis auf regulatorische Hürden. Insbesondere die Hospital Exemption Rule (HER) bietet theoretisch niederschwelligen Zugang, bleibt in Österreich aber rechtlich unklar. Der Beitrag beleuchtet Anwendungsoptionen, Risiken und Praxisdefizite sowie Perspektiven für eine rechtssichere Umsetzung. Der Artikel analysiert die regulatorischen Instrumente für ATMPs in Österreich und zeigt auf, warum die HER bislang kaum genutzt wird. Zugleich werden Empfehlungen für eine rechtssichere und patientenorientierte Anwendung gegeben.

Background: Myocardial infarction (MI) remains a critical focus in cardiovascular research, with in vitro models serving as essential tools for investigating pathophysiological mechanisms and evaluating therapeutic strategies. Despite their widespread use, the clinical relevance of these models is often assumed rather than rigorously validated. Methods: In this review, we systematically examined 28 studies from the last decade that employed in vitro co-culture models of MI, selected via a PubMed search according to pre-defined criteria. Each study was analysed with respect to ischaemia/reperfusion (I/R)-mimicking conditions applied, species and cell types used, and strategies for verifying clinical relevance. Results: Our analysis revealed considerable heterogeneity in experimental design. Protocols for inducing I/R stress and the duration of treatment varied widely between studies, underscoring a lack of methodological standardization. Cell sources included swine, rat, mouse and human-derived cells, with nearly half of the studies utilizing cross-species combinations – often without addressing the implications for translational validity. Verification strategies were inconsistently applied and frequently limited to basic endpoints such as cell viability and oxidative stress assays. Some studies also employed in vivo models to validate in vitro findings. Conclusions: To enhance translational potential, future studies should prioritize human-derived cells, standardized I/R protocols and verification strategies that better recapitulate MI pathology.