Biology subjects

Monroy, M.

Publications and source records attributed to Monroy, M..

2 recordsLinked to original sources

bioRxiv2026

Porcine Left Atrial and Ventricular Thick Filaments Exhibit Distinct Resting Structures and Calcium-dependent Responses

The heart maintains systemic perfusion through the coordinated function of its four chambers: the left and right atria and ventricles. Each chamber has distinct structural, functional, and molecular properties tailored to its role in circulation, which may result in chamber-specific differences in myofilament structure and regulation between atria and ventricles. To test this hypothesis, we employed muscle mechanics and X-ray diffraction to investigate functional and structural differences in porcine left atrial (LA) and left ventricular (LV) tissue. Here, we report the first X-ray diffraction study of atrial tissue, demonstrating that under resting conditions, myosin filaments in LA adopted a more ON-like, structurally distinct configuration compared with those in LV. Under contracting conditions, LV generated greater force and exhibited higher sinusoidal stiffness than LA across multiple calcium concentrations. LA showed faster kTR than in LV, with no calcium-dependence, in contrast to the calcium-dependence of kTR seen in LV. Structurally, the distinct myosin head configuration seen in the relaxed LA persisted during contraction. Furthermore, using the troponin inhibitor MYK-7660 to inhibit active contraction, we showed that, unlike LV, LA showed no direct calcium-dependent thick filament activation, reconciling discrepancies between fast rat and slow porcine ventricular myocardium regarding calciums role in thick filament regulation. Altogether, our study reveals that LA myosin filaments adopt a molecular architecture and regulatory mechanism distinct from their LV counterparts, suggesting that myosin filament structure and regulation have evolved differently to meet the unique functional demands of each cardiac chamber. Moreover, atrial disease is often associated with cardiomyopathy-related genetic variants, highlighting the atrial myocardium as an important therapeutic target and understanding atrial-specific regulatory mechanisms provides new insights into therapeutic strategies for atrial diseases.

physiology↗

bioRxiv2025

Establishing Comprehensive Transthoracic Echocardiography Reference Ranges for Mouse Models: Insights into the Impact of Anesthesia, Sex, and Age

Mouse models play a critical role in cardiology research, offering valuable insights into the molecular mechanisms, genetics, and potential treatments for cardiovascular diseases. However, the ability to transfer findings in mice between studies is limited by the absence of standardized protocols and valid reference values for the assessment of normal cardiac function in mice. This study aims to establish comprehensive transthoracic echocardiography (TTE) reference ranges for mice, particularly focusing on C57BL/6N wildtype controls. The study, which includes data from over 15,000 mice through the International Mouse Phenotyping Consortium (IMPC), highlights how variables such as sex, age, body weight, and anesthesia affect TTE parameters. The findings showed that anesthesia is the primary predictor of variability in cardiac function. Isoflurane and tribromoethanol anesthetized mice presented with modified cardiac function compared to conscious mice. Additionally, we observed minimal sex differences in cardiac morphology and function, except for small variations influenced by anesthesia. The effects of aging on cardiac function were modest, characterized by a decrease in heart rate and subtle changes in ventricular dimensions without evidence of pathological remodeling, likely attributable to disease-free cardiovascular aging. Validation of the reference ranges across multiple mouse strains showed that these values provide a reliable baseline for experiments involving cardiac function in mice. The data underscore the importance of using anesthesia-specific reference values when interpreting TTE results, ensuring robust comparisons in genetic and pharmacological studies. These reference ranges serve as quality assurance tools for future cardiac studies in mice, offering insights into typical TTE parameter values, supporting the detection of experimental perturbations, and contributing to more effective translation of findings from mouse to human.

genetics↗