Maria Nacher Espuig

Maria Nacher Espuig, PhD

Research Instructor, Department of Medicine

Summary

Cardiovascular diseases (CVDs) remain the leading cause of death globally, with atherosclerosis being a key contributing factor. Modifiable risk factors, such as high cholesterol and obesity, play significant roles in the development of atherosclerosis and CVDs. Addressing these factors is crucial to mitigating the global impact of CVDs.

Statin therapy has been the cornerstone of hypercholesterolemia management for decades, effectively lowering low-density lipoprotein (LDL) cholesterol levels and reducing the incidence of myocardial infarction and stroke. Despite their proven efficacy, poor adherence to statin regimens remains a persistent challenge, leading to increased mortality in patients with atherosclerotic CVD. Intermittent adherence to statins results in fluctuating cholesterol levels, a phenomenon termed intermittent hypercholesterolemia, which triggers pro-inflammatory responses through its impact on the innate immune system. This dynamic is hypothesized to involve the activation of innate trained immunity, wherein innate immune cells, such as monocytes and macrophages, exhibit a memory-like response to subsequent exposures to an initial stimulus. Emerging evidence suggests that this immune training extends to hematopoietic stem and progenitor cells (HSPCs), which are responsible for the generation of all blood and immune cells. These epigenetically reprogrammed HSPCs likely play a pivotal role in sustaining chronic inflammation and accelerating atherosclerotic progression.

Our primary research focuses on elucidating the role of innate trained immunity and its influence on HSPCs in the context of atherosclerosis and intermittent lipid lowering. I am particularly interested in understanding how epigenetic modifications in HSPCs contribute to immune training and the intricate relationship between HSPCs, the epigenetic reprogramming of immune cells, and their roles in the progression and regression of atherosclerosis. By integrating cellular assays, such as clonogenic assays, animal models, and human clinical studies, we aim to comprehensively map the molecular and functional alterations in HSPCs under inflammatory and metabolic stress conditions. These insights help reveal the mechanisms by which hypercholesterolemia-induced trained immunity establishes a pro-inflammatory state at the stem and progenitor cell level, promoting rapid immune responses and exacerbating atherosclerotic plaque development.

In parallel, our translational studies seek to bridge fundamental discoveries with clinical applications. We aim to develop targeted therapies that modulate HSPC behavior and trained immunity to resolve inflammation and reverse atherosclerosis. Such approaches have the potential to transform cardiovascular disease management, particularly in individuals facing metabolic and inflammatory challenges.

Additionally, we are investigating obesity as a critical risk factor for CVD. Bariatric surgery, the most effective intervention for substantial and sustained weight loss, offers a unique opportunity to study the immune landscape in the context of obesity resolution. As a dietitian and nutritionist, my research extends to evaluating the effects of bariatric surgery-induced weight loss on inflammation, with a focus on the immune response during both short- and long-term recovery in obesity-associated cardiovascular conditions.

By leveraging single-cell technologies and computational analyses, we aim to unravel the intricate pathways underlying immune cell reprogramming, inflammation, and disease resolution in CVD and obesity. This integrated approach provides a deeper understanding of the intersection between trained immunity, HSPC epigenetics, and cardiovascular health. Ultimately, our research aspires to translate these insights into innovative therapeutic strategies, offering new avenues for the prevention and management of CVD, particularly in patients with dyslipidemia and metabolic disorders.

Is this your profile?

PhD from University of Barcelona