Cardiovascular and Respiratory Pathology/Other Systemic Diseases

Vascular Pathophysiology


Cód. SSPA: IBiS-D-04

Our area of work is the Molecular Pathophysiology of the Cardiovascular System.

Research Lines:

  • Aneurysmal Subarachnoid Hemorrhage (aHSA)

Cerebral vasospasm (CV) is one of the most serious complications of aHSA. We study the role of vasoreactivity and inflammation (leukocyte-endothelium interaction) in this pathology. Previously, in experiments carried out in collaboration with the Neurocritics unit of the HUVR we have observed that: a) Protein kinase C (PKCα) inhibits the RhoA/Rho kinase (ROCK) pathway in arterial smooth muscle cells, and the co-application of PKC and ROCK inhibitors produces a synergistic vasorelaxant effect in animal models; and b) the amount of RhoA protein in the first 24 h after bleeding is increased in peripheral blood mononuclear cells (PBMCs) of patients with aHSA, and this increase is related to patient severity and VC.

The group studies the role of RhoA in the PBMCs of patients with aHSA, to analyze its possible use as a predictive biomarker for this pathology. In addition, we studied whether inhibition of PKC and RhoA pathways could exert a pleiotropic effect, decreasing vascular contractility and decreasing leukocyte-endothelial interaction. On the other hand, we have recently incorporated the study of the role of high-density lipoproteins (HDL) in aHSA. We have observed changes in the amount, composition and functionality of HDL in the plasma of patients with this pathology. We will study the role of these alterations in the development of aHSA and their possible relationship with VC. 

We have also initiated the preclinical study of VC in an in vivo mouse model of SAH. These experiments will make it possible to analyze the macro and microcirculation of the brain through the use of a double-photon microscope.

  • Cardiac canalopathies

We study the pathophysiological role of ion channels in cardiac muscle cells, with special interest in mutations in the channels (and proteins associated with them), responsible for different types of arrhythmias (Brugada Syndrome, Long QT Syndrome, etc.). Currently, we are studying a family of patients with Jervell and Lange-Nielsen syndromes and long QT, in which several of its members carry different combinations of mutations in the KCNQ1, KCNH2 and AKAP9 genes. These different combinations give rise to different phenotypes. We carry out molecular and functional studies to determine the effect of these mutations, in order to define their role in the determination of the different phenotypes observed.  

Share on: