Periodic Reporting for period 2 - InflammaTENSION (A study of the roles of the immune and inflammatory systems in hypertension.)
Reporting period: 2018-11-01 to 2020-04-30
1. We found that a small piece of genetic material could explain why arteries become increasingly stiff , which happens in high blood pressure and why blood vessels age faster in hypertension. If found in patient blood samples, this molecule could give doctors an early warning of artery problems, and help people get treatment more quickly. In this study we used many in vivo, in vitro as well as translational human approaches to identify how small molecule of microRNA that is present in lymphocytes, white blood cells responsible for fighting infections, can direct these cells to blood vessels. We pinpointed a piece of genetic material called a micro-RNA – specifically one called miR-214 - which makes white blood cells called T-cells move to the fatty tissue around arteries. Once in this tissue, the T-cells cause inflammation, causing the artery structure to become damaged and increasing their stiffness. This work is the first to link a cascade of damaging events linked to blood pressure to higher levels of miR-214. This is responsible, at least in part, for the process of accelerated vascular ageing characterized by stiffer vessels. We have shown this not only in disease models but also provided proof of concept in patients with hypertension. his work is the first to link a cascade of damaging events linked to blood pressure to higher levels of miR-214. The paper was featured in press release and in newspapers and tweets worldwide (e.g. https://news.cision.com/kidney-research-uk/r/new-research-gives-clues-to-artery-problems-in-high-blood-pressure,c3094985 ; AND: https://www.heraldscotland.com/news/18436383.new-treatment-silent-killer-horizon-scottish-scientists-make-major-breakthrough-high-blood-pressure/)
2. We observed that probably the most common inflammation in human body – periodontitis is causally linked to blood pressure control. We used a series of approaches starting from hypertension model studies, through a genetic study and clinical interventional trial reaching a systematic review and metanalysis style. These studies were received with very high interest by public, as have been picked up by 42 news outlets, blogged and tweeted by over 200, quoted on Facebook pages and referenced in Wikipedia. Our main paper has been widely discussed at conferences and also as podcasts (available on Spotify)
3. We have shown, using a large population analysis a clear link in humans between blood lymphocytes and blood pressure levels (using a large population of >7500000 people in the largest blood pressure genetic study). These studies provide in man, populational evidence supporting the main InflammaTENSION thesis that inflammation is essential in regulating blood pressure. This study has reached visibility through social media engagement by 2 main scientific societies in cardiology - American Heart Association as well as European Society of Cardiology.
In progress so far we have already provided comprehensive evidence supporting role of inflammation in hypertension using epidemiological and genetic tools as well as have shown proof of concept of using this knowledge in human therapy. We are working on identifying further specific novel mechanisms.