Branko Braam (PhD, Utrecht University)

Professor
Adjunct Nephrology

11-132 Clinical Sciences Building
University of Alberta
Edmonton, Alberta
Canada T6G 2G3

Tel: 780 492-3322
Fax: 780 407-7771

branko.braam@ualberta.ca
Branko Braam's pubmed articles


Research Description

Monocyte function and gene expression signatures in hypertension
Hypertension induces a systemic condition associated with a high risk to develop atherosclerosis, and consequently cardiovascular events. We recently discovered that systemic consequences of hypertension are reflected in modulated gene expression profiles of leukocytes. Diminished expression of anti-inflammatory genes and increased expression of genes related to blood pressure (e.g. the AT1 receptor) was observed. The design of that study did not allow analysis of individual gene expression signatures.

The observation creates an interesting option: if hypertension is associated with a systemic state that heralds atherosclerosis and can be recognized in an abnormal gene expression pattern of easily obtainable circulating cells, normalization of this pattern might be the most critical component of antihypertensive therapy in reducing risk. Moreover, when signatures of specific driving forces of hypertension could be recognized in circulating cells, treatment could be specifically targeted to counter those driving forces. Specifically, pathways modulated by enhanced activity of the renin-angiotensin system (RAS) and diminished nitric oxide (NO) bioavailability, two of the central pathophysiological mechanisms in the development of hypertension and cardiovascular damage, could serve to more specifically monitor treatment. It is largely unknown how increased angiotensin II (AngII) and NO deficiency affect leukocytes, in particular monocytes, key players in the initiation and progression of atherosclerosis. Hypertension frequently coincides with other cardiovascular risk factors. How hypertension, together with these factors affects the function of monocytes is also unclear.

The overall hypothesis is that enhanced AngII and diminished NO bioactivity together with increased hydrostatic pressure cause specific transcriptional responses in pro-atherogenic pathways (inflammation-, redox-, RAS-, adhesion-related genes) in monocytes (and other circulating cells) in vitro. These responses can be recognized in monocytes of patients with hypertension, and can form the basis of molecular characterization of the systemic consequences of hypertension.

Studies will be performed in cultured EC and monocyte cell lines, in circulating cells in animal models of hypertension and in leukocytes and monocytes obtained from patients with hypertension by transcriptome analyses and by analyses of cell function. The studies will support a molecular characterization of the systemic consequences of hypertension. This will assist in targeting affected pathways more specifically, aiming at a more effective reduction of cardiovascular risk associated with hypertension.


Selected publications