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Role of genetic background in remodeling of small arteries in hypertension.

 

Description

Small artery remodelling is heterogeneous in animals and patients. Even within one specific model, the spontaneously hypertensive rat (SHR), small mesenteric arteries were reported to show inward remodeling in one case1, and hypertrophic remodeling in another2.


Hypothesis: Based on the current insight in the genetic differences among substrains of SHRs3, we hypothesized that the genetic background is a critical determinant in vascular remodeling. Ongoing work in the current ‘Smart’ ITN substantiates this hypothesis. Thus, we found that substrains of both SHR and their normotensive controls, the Wistar Kyoto rat (WKY) show marked differences in vascular remodeling, blood pressure, blood pressure development, endothelial function, and other parameters. Tissues that have been collected from various substrains of SHR and WKY rats are currently analysed with a combination of DNA microarray analysis (mRNA), miChip (micro-RNA) analysis and proteomics in collaboration with the KC partner.


Objectives: In this project we aim to unravel the role of the genetic background in hypertensive resistance artery remodeling. More precisely, we aim to determine the pathways associated with inward remodeling versus those associated with hypertrophic remodeling.


Training: The ESR will be trained to test the role of the selected candidates coming from the previous analysis. These will be tested for their role in vascular remodeling using pharmacological and genetic gain- and loss of-function experiments both in vitro (isolated arteries in culture) and in vivo, for which expertise is provided by the DMT partner and the host institute.


1 Circulation 1999, 30;100(22):2267-75.       2 Clin Sci (Lond) 2001, 101(4):385-93.       3Hypertension 2005 Apr;45(4):698-704.

Publications

Palao, T., Swärd, K., Jongejan, A., Moerland, P.D., de Vos, J., van Weert, A., Arribas, S.M., Groma, G., vanBavel, E., & Bakker, E.N.T.P. Gene Expression and MicroRNA Expression Analysis in Small Arteries of Spontaneously Hypertensive Rats. Evidence for ER Stress. PLoS One, doi: 10.1371/journal.pone.0137027.

 

Palao, T., Rippe, C., van Veen, H., VanBavel, E.T., Sward, K., & Bakker, E.N. (2016). Thrombospondin-4 knockout in hypertension protects small artery endothelial function but induces aortic aneurysms. Journal of Physiology – Heart and Circulatory Physiology, 310, 1486-1493.

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Ph.D student / post-doc

Teresa Palao Garcia

 

Principal Investigator

Prof. van Bavel