Andrew MacKenzie

Cardiovascular disease is the single leading cause of death and disability in the world (responsible for almost 1 in every 3 deaths). Dysfunction of endothelial cells, a cell type that lines the surface of every blood vessel, plays a critical role in the development and progression of cardiovascular disease but as yet we do not have effective therapeutic means to protect or restore activity of this key cell type. My research focuses on the role of endothelial cells as a regulator of vascular smooth muscle cell activity and how this can be is disrupted by the inflammatory conditions that occur in diseases such as obesity, diabetes mellitus, preeclampsia and rheumatoid arthritis. Understanding more about how endothelial cells become dysfunctional will greatly enhance our insight into the cellular processes that underlie the cardiovascular disease and help find means to prevent the its devastating consequences, such as heart attack and stroke.

I have established an ex vivo vascular assessment suite allowing the determination of both macro- and micro-vascular reactivity i.e. real-time recording of contraction and relaxation of isolated blood vessels. The key advantage of ex vivo analysis of vascular reactivity is that the blood vessel is free from hormonal or neural influence and in an environment which allows for accurate probing of cellular pathways. Furthermore, through my partnership with the Centre of Musculoskeletal Science at Glasgow University, we can also determine blood flow in vivo with use of a laser Doppler technique. Moreover, access to techniques such as PCR, immunohistochemistry, western blotting and ELISA allows for a multi-faceted multi-disciplinary approach to exploring vascular dysfunction.

My current research investigates the mechanisms underlying vascular dysfunction found in several diverse disorders. Specifically we are exploring the role of the angiotensin 2 type 1 receptor as a mediator of vascular dysfunction found in rheumatoid arthritis. Furthermore we are analysing the role of adipose tissue as a regulator of vascular reactivity and how with can be modified by proteinase-activated receptor 2 in conditions of obesity. In addition we are analysing human placental artery function in relation to interleukin levels to investigate potential a route by which preeclampsia may develop. Moreover we are examining flavonoids and other dietary supplements for their putative protective action against the detrimental influence of glucose vascular reactivity.

My aim is to garner further insight into the cellular mechanisms underlying vascular disorder and to utilise this knowledge to highlight novel routes of therapy and, along with industrial partners, develop targeted pharmaceutical interventions to prevent or alleviate this most devastating of diseases.