Biology subjects

Cartwright, E. J.

Publications and source records attributed to Cartwright, E. J..

3 recordsLinked to original sources

bioRxiv2026

Microtubule-associated protein 1S (MAP1S): a cardioprotective factor against post-myocardial infarction remodeling via apoptosis inhibition

Adverse cardiac remodeling following myocardial infarction (MI) are driven by processes including autophagy and apoptosis. While microtubule-associated protein 1S (MAP1S) is known to regulate autophagy, its role in the cardiac pathological conditions remains unclear. This study aimed to elucidate the role of MAP1S and its underlying mechanisms in pathological cardiac remodeling. Following MI, MAP1S knockout mice exhibited increased mortality, impaired cardiac function, and elevated apoptosis. Similarly, MAP1S silencing in cultured cardiomyocytes augmented apoptosis under oxidative stress. Mechanistic investigation revealed potential link to the Hippo pathway. MAP1S knockdown in cardiomyocytes increased Mammalian Ste-20 like 1/2 (MST1/2) activation and reduced Yes-associated protein (YAP) activity, potentially explaining apoptosis regulation. Conversely, MAP1S overexpression reduced apoptosis and positively modulated autophagy. Importantly, in vivo modRNA-mediated MAP1S overexpression protected against apoptosis and adverse remodeling. This study reveals that MAP1S protects the heart from excessive apoptosis and adverse remodeling following MI, likely by modulating the Hippo signaling pathway.

cell biology↗

bioRxiv2025

Regional Vulnerability of Cardiac Chambers to Radiotherapy: A Multi-Omics Perspective

The heart is highly vulnerable to radiotherapy (RT)-induced injury, leading to molecular and structural remodeling collectively termed radiation-induced cardiac toxicity (RICT). Although several biological pathways have been implicated, the regional, cardiac-specific molecular responses to radiation exposure remain incompletely understood. Here, a multi-omics approach was adopted to longitudinally characterise the unique responses to radiation of the heart base (including ventricular base and right atrium), or the heart apex. Ventricular base irradiation induced a cardiomyopathy phenotype, with pronounced molecular perturbations in metabolism and electrical conduction, while changes related to tissue structure were predominant following apex-directed RT. In the right atrium, irradiation drives fibrotic tissue remodelling, leading to an increased propensity for atrial fibrillation, underpinned by changes in sarcomere organisation. This study represents a comprehensive characterisation of differential spatiotemporal radiation effects in the heart and highlights biological and functional pathways that are potentially clinically actionable for cardiac radioprotection and monitoring.

cell biology↗

bioRxiv2025

Dysferlin Regulates Cardiac T-tubule Structure and Excitation-contraction Coupling in Isolated Cardiac Myocytes at Rest and in Response to Acute Hypo-osmotic Stress and is Protective Against Arrhythmias in Langendorff-perfused Hearts

Dysferlin is a membrane-associated protein that supports skeletal muscle function such that mutations in the DYSF gene can cause muscular dystrophy. Growing evidence suggests dysferlin regulates cardiac function, but this is less well understood. Tight regulation of the cardiac transverse-(T)-tubule network and excitation-contraction (EC) coupling mechanism is essential for healthy cardiac physiology. Remodelling of T-tubules and the EC coupling mechanism is observed during periods of cardiac stress and pathologies, promoting arrhythmias. However, little is known about how these processes are regulated and any protective mechanisms which may limit detrimental effects. Using a global dysferlin knockout (KO) mouse we have shown that the loss of dysferlin leads to a decrease in T-tubule density and the amplitude and rate of decay of the systolic Ca2+ transient but a narrowing of the dyadic cleft. Electrical mapping of ex vivo DYSF KO hearts shows they are more susceptible to ventricular arrhythmias. To induce stress, we used hypo-osmotic shock injury (OSI) to damage T-tubule networks in cardiac myocytes, in vitro. OSI increased T-tubule fragmentation and caused dysregulation of intracellular Ca2+ handling in dysferlin KO cells relative to WT controls. Finally, we observed that a natural decline in WT cardiac dysferlin abundance, which may contribute to the natural age-dependent maladaptive T-tubule remodelling that occurs in the mammalian ventricle. In summary, these findings demonstrate an essential role for dysferlin in cardiac physiology, especially during conditions of stress, which is decreased in normal ageing.

physiology↗