Project 14

Novel inflammatory and anti-inflammatory mechanisms of vascular damage in hypertension

Inflammation is a newly recognised mediator of cardiovascular damage in hypertension. We hypothesize that an inflammatory process mediated by interferon-stimulated genes and oxidative stress as well as an inefficient resolution of inflammation by proresolving lipid mediators, are responsible for the vascular and cardiac damage observed in hypertension. The ESR will work in collaboration with other ESRs to identify novel aspects of inflammation and resolution of inflammation that participate in hypertension-associated cardiovascular damage both at preclinical and clinical level, and to evaluate the therapeutic potential of proresolving mediators.

The ESR will work with cultured murine and human endothelial and vascular smooth muscle cells and with pharmacologically treated mice. Transgenic mice targeting different components of interferon signalling or expressing elevated levels of proresolvin lipid mediators will be also used. Determination of inflammatory mediators (i.e cytokines and oxidative stress) will be done using standard techniques or high-throughput gene expression analysis. The physio(patho)logical impact of these mediators on endothelial function, vascular stiffness and cardiovascular remodelling and function will be evaluated. Furthermore, the potential impact of the specific mediators on cardiovascular damage will be confirmed in human samples.

Planned secondments: 1 month at Attoquant (Vienna) on LC-MS/MS determinations; 3 months at University of Glasgow (Profs. Touyz and Delles) to investigate levels of oxidative stress markers and inflammatory and proresolving mediators in samples from preclinical models and patients; 2 months at Maastricht University (Profs. Stehouwer and Schalkwijk) to perform measurements of circulating specific inflammatory and proresolving mediators in human samples.

Requirements:

  • Qualifications: MSc degree in a biomedical related field; animal FELASA certificate is an asset.
  • Experience: previous experience in cell culture or animal work is desirable.
  • Knowledge & skills:experience with common molecular techniques; animal work.
  • Attitude and disposition: Highly enthusiastic about research and willing to learn; creative and independent thinker; team worker.