Blood vessel endothelium crosses each and every tissue and presents unique structural and functional properties in each vascular bed. This cellular heterogeneity is reflected by the structural and functional heterogeneity of the whole endothelium as a complex system. Due to its location, the endothelium is exposed to all kinds of physiological and pathological stimuli and constitutes the first barrier to many drug interventions.
This organ has the capacity to constantly adapt to environmental changes by modulating vasomotor tone, haemostatic balance and inflammatory reactions, among other responses. Endothelial activation could lead to an irreversible state known as endothelial dysfunction that, in a broad sense, leads to various non-adaptive alterations of the functional phenotype that constitute a net liability to the host.
Our group has extensive experience in the study of the endothelial dysfunction that develops in association with different vascular pathologies, such as the early complications associated with hematopoietic cell transplantation, obesity, chronic kidney disease, thrombotic microangiopathies and sepsis.
We also explore strategies for the protection of this endothelial dysfunction to improve patient health. In this regard, one of our main interests is to evaluate different compounds that potentially exhibit the capacity to protect the endothelium and to decipher their mechanisms of action.
Our main lines of research are:
- To characterize the endothelial activation and dysfunction associated with cardiometabolic diseases through in vitro models.
- To elucidate the mechanisms that lead to endothelial dysfunction.
- To investigate agents with potential protective effects on the endothelium to prevent complications.
- To find soluble markers with prognostic and diagnostic value for vascular complications.
- To study complement pathways and complement deficiencies in thrombotic microangiopathies.
- To assess platelet physiology and alterations of haemostasis by using perfusion devices to explore adhesive and cohesive properties of platelets under flow conditions.
Hematopoietic cell transplantation (HCT) has been the major curative therapy for several hematological, metabolic and neoplastic disorders. However, the efficacy of this procedure is limited by life-threatening complications, the most important of which is graft versus host disease (GvHD), which has a high mortality rate. Through our research, we aim to answer the following questions:
- What are the pathophysiologic mechanisms that characterize endothelial dysfunction?
- How can we avoid the vascular complications associated with hematopoietic cell transplantation?
- Which is the role of the complement system in vascular complications?