CChronic heart failure presents a tough challenge, not only because of its impact on the heart but also due to the changes it causes in skeletal muscles, which can affect a person’s overall health. A significant study conducted by Dr. Sofia Gitler, Ibrahim Ramirez-Soto, Professor Dr. Aura Jiménez-Garduño, and Professor Dr. Alicia Ortega from the Universidad Nacional Autónoma de México provides new perspectives on how muscles adapt to this condition. The findings, published in the International Journal of Molecular Sciences, highlight the biological adjustments that help preserve muscle function during prolonged heart stress.
“Difficulty with physical activity and muscle weakness are common symptoms of chronic heart failure,” explained Dr. Gitler. However, the study uncovers surprising resilience in muscle performance, offering potential new paths for treatment.
Dr. Gitler et al. explored the details of muscle cell behavior using a rat model of chronic heart failure created through a surgical procedure. A rat model is an experimental system using rats to mimic human diseases for research. Three months after inducing heart failure with extensive myocardic infarction, the team observed remarkable chemical changes in specific parts of the skeletal muscle cells. “The increased activity of proteins that manage calcium and glucose in muscle cells appears to provide protection against energy loss and fatigue,” noted Dr. Gitler et al. Calcium is essential for muscle contraction, while glucose serves as a primary energy source. These changes were profound—activity of calcium-regulating proteins increased fivefold, while glucose transport proteins rose sevenfold compared to unaffected rats.
One of the most notable findings was that the mechanical properties of the muscles, such as their ability to contract and recover from fatigue, remained unaffected by chronic heart failure. Mechanical properties refer to how muscles perform physical tasks, including generating force and enduring strain. This discovery challenges long-held beliefs about inevitable muscle deterioration and suggests that the body has built-in ways to counteract these effects at a cellular level.
Dr. Gitler and colleagues highlighted the role of nitric oxide, a molecule known for improving blood flow. Blood flow ensures that muscles receive enough oxygen and nutrients to function. Its levels were higher in rats with chronic heart failure, which may help maintain proper circulation and muscle function. “This could explain why muscle strength was preserved despite the widespread effects of heart failure,” said Dr. Gitler.
Moreover, the study drew attention to the glucose transport protein, which responds to insulin to support energy supply in muscles. Insulin is a hormone that helps regulate blood sugar levels. The increased levels of this protein help the muscles access energy during prolonged activity. Similarly, the enhanced activity of calcium-regulating proteins prevents dangerous calcium buildup in the cells, protecting them from damage.
Looking at the broader implications, the researchers believe that understanding these natural adaptations could lead to better treatments. Treatments could involve enhancing the body’s ability to regulate energy and calcium in muscles. Methods that boost glucose transport or calcium-regulating proteins might help people suffering from muscle fatigue or weakness caused by chronic conditions.
Although the findings are promising, Dr. Gitler and collegues emphasize the need for further studies to see if these mechanisms also apply to humans and how they could be targeted through treatments. This research provides a deeper understanding of how chronic illnesses affect muscles and offers hope for developing effective interventions to improve patient outcomes.
Journal Reference
Gitler, S., Ramirez-Soto, I., Jiménez-Graduño, A., Ortega, A., “Calcium ATPase (PMCA) and GLUT-4 Upregulation in the Transverse Tubule Membrane of Skeletal Muscle from a Rat Model of Chronic Heart Failure,” International Journal of Molecular Sciences, 2024. DOI: https://doi.org/10.3390/ijms252011180
About the Authors
Dr. Sofia Gitler is a medical doctor specializing in Internal Medicine, who earned her medical degree from Universidad La Salle in Mexico City and completed her specialty training at the National Autonomous University of Mexico (UNAM). She has participated in a variety of biomedical studies through research collaborations at the National Institute of Genomic Medicine and the Department of Biochemistry at UNAM’s Faculty of Medicine. Clinically, she has practiced at the ABC Medical Center in Mexico City, focusing on comprehensive patient care. Her primary research interests target the health and well-being of older adults, with a particular emphasis on muscle and brain function as they relate to aging.
Dr. Alicia Ortega earned her M.D. from the Faculty of Medicine at the National Autonomous University of Mexico (UNAM) and completed her undergraduate internship at the University of Maryland School of Medicine in Baltimore. She then received her Ph.D. in Science from the University of Waterloo in Canada. Following her doctoral studies, she held postdoctoral research positions in the Departments of Biophysics and Biochemistry at the University of Maryland, the Department of Muscle at the Boston Biomedical Research Institute (BBRI), and in the Department of Chemistry at the Massachusetts Institute of Technology (MIT). She also served as a Visiting Professor at the Max Planck Institute of Biochemistry in Germany as a fellow of the Alexander von Humboldt Foundation.
Dr. Ortega’s research focuses on the biochemical and physiological aspects of skeletal muscle, excitable cell membranes, and membrane protein stability. Over the past 30 years, she has investigated phenomena such as fatigue, exercise adaptation, and muscular dystrophy at the subcellular level, and more recently has explored the brain’s role in controlling movement in conditions like Parkinson’s and epilepsy. She is currently a Professor and Researcher in the Department of Biochemistry at the Faculty of Medicine, UNAM, and a member of both the National Academy of Medicine of Mexico and the Mexican Academy of Science.
