Neuropsychiatric Dysregulation and Cardiovascular Disease: Identification of Novel Personalized Therapeutic Targets
Stress, anxiety, and depression are now recognized as independent cardiovascular risk factors and are closely associated with a significant worsening of clinical outcomes, suggesting potential limitations of conventional therapies in patients affected by these comorbidities.
This project has a twofold objective. First, it aims to advance our understanding of disease pathogenesis by investigating the molecular and cellular mechanisms that mediate the interplay between the nervous and cardiovascular systems. Second, it seeks to identify predictive biomarkers and develop personalized therapeutic strategies capable of optimizing treatment efficacy in this particularly vulnerable patient population.
Neurotrophins and Cardiovascular Health: From Molecular Mechanisms to Clinical Risk
Neurotrophins play a fundamental role in cardiovascular physiology and pathology, influencing the development and homeostasis of the heart, blood vessels, and the neural circuits that regulate cardiovascular function. Alterations in their expression and activity are frequently observed in a variety of cardiovascular conditions, including atherosclerosis, hypertension, diabetes mellitus, acute myocardial infarction, and heart failure.
Within this framework, our research focuses particularly on mature Brain-Derived Neurotrophic Factor (mBDNF) and its precursor, pro-BDNF, two molecules that exert distinct yet complementary biological effects. mBDNF is well known for its neuroprotective and pro-angiogenic properties, whereas pro-BDNF may induce opposing effects by promoting apoptotic and inflammatory pathways.
The aim of this project is to elucidate the role of mBDNF and pro-BDNF in cardiovascular disease by investigating the molecular mechanisms regulating their release into the circulation and their effects on megakaryopoiesis and the activation of platelets, leukocytes, endothelial cells, and cardiomyocytes. In collaboration with national and international partners, we are examining how the delicate balance between mBDNF and pro-BDNF influences thrombosis and coronary myocardial infarction, with the goal of identifying novel diagnostic and therapeutic approaches.
Cell-to-Cell and Inter-Organ Communication in Myocardial Infarction and Thrombosis
Communication and interaction among different cell types—including platelets, leukocytes, endothelial cells, cardiomyocytes, fibroblasts, and adipocytes—are essential processes that determine atherosclerotic plaque stability, thrombus formation and resolution, as well as tissue injury, regeneration, and repair following ischemic events such as myocardial infarction and stroke.
Our research focuses on the dynamic communication between the heart and other organs, particularly the brain, which is fundamental for maintaining cardiovascular homeostasis. Despite growing evidence of a causal relationship between brain injury and cardiovascular morbidity and mortality, the mechanisms through which a “distressed” brain influences cardiac and vascular function remain poorly understood.
We aim to identify and characterize the communication pathways operating both between cells within the same tissue and across different tissues and organs (e.g., heart, vessels, blood, and brain). A major focus is placed on the release of soluble factors and small extracellular vesicles (sEVs). We are investigating how sEVs transport not only molecular signals but also mitochondrial components—or even entire mitochondria—and how these complex cargoes may positively or negatively affect the prognosis of patients with cardiovascular disease.
Within this context, particular attention is devoted to platelets. Often considered a “peripheral mirror of brain status” because of their common embryological origin with neurons and their shared neurotransmitters and receptors, platelets are emerging as key mediators within the intricate network of neuro-cardiovascular communication.
