Mark Miller is a Reader (Research Scientist) working in the Centre for Cardiovascular Science at the University of Edinburgh (United Kingdom) funded by the British Heart Foundation.

Mark obtained his degree in Pharmacology at the University of Edinburgh. He then pursued a PhD in the cardiovascular effects of novel nitric oxide donor drugs at the same Institute, continuing his interest in this topic in postdoctoral positions at the University of Strathclyde.

Over the last 15 years, Mark’s research has addressed the health effects of air pollution. A notable focus has been the biological pathways by which the particles in vehicle exhaust cause adverse effects in the cardiovascular system. He also has an interest in the potential for manufactured nanoparticles to cause harm to the cardiovascular system. His work encompasses a broad range of approaches from in vitro assays, in vivo models of disease and controlled exposure to pollutants in human subjects.

Mark has published more than 90 articles in peer-reviewed journals and contributed to the acquisition of £~20 million GBP in research funding. He has given over 50 invited presentations across the scientific community, the third sector and public engagement.

Mark is an Editor of the journal Particle & Fibre Toxicology. He is a member of the World Heart Federation Air Pollution Expert Group and the Environmental Protection Scotland Air Quality Expert Advisory Group, as well as a Special Adviser to the UK Clean Air Champions Knowledge Exchange Group. He is also an Expert Member of the Committee on the Medical Effects of Air Pollution (COMEAP), which advises the UK governmental Department of Health on this subject.

Mark’s research findings have received extensive coverage in the national and international media, and featured in documentaries on UK television. His work contributed to the Department of Cardiology’s Queens Anniversary Award 2014-16 for outstanding contribution to scientific research. His work was highlighted as a case study in the DEFRA (UK Government) Clean Air Strategy 2019. He has recently been acknowledged for his contributions to the 2021 World Health Organisation Global Air Quality Guidelines and the Chief Medical Officer for England’s Annual Report: Air Pollution (2022).

Air pollution imposes a huge burden on health and is associated with over 7 million premature deaths globally every year. While air pollution damages the lung, over half of the deaths attributed to air pollution are from cardiovascular causes. Research in our centre has demonstrated that acute exposure to diesel exhaust causes many detrimental actions on the cardiovascular system in human volunteer studies. Parallel in vitro studies went on to show that the specifically the particles in diesel exhaust impair vascular function and that prolonged in vivo exposure to these particles promoted the development of the vascular disease atherosclerosis.

In 2017, in our “gold study”, we demonstrated that the small size of nanoparticles allows them to pass from the lung into the blood. Furthermore, the particles preferentially built up at areas of vascular disease, where they are likely to exacerbate disease and potentially trigger a cardiovascular event. This mechanism could also account for the growing list of epidemiological associations between air pollution and conditions of almost every organ of the body.

Previous projects have also investigated:

• The use of acellular methods to measure free radical generation from various particulates, including superoxide free radicals which can scavenge nitric oxide from endothelial cells (BHF-funded research)

• The role of chemicals on the surface of diesel exhaust particles in driving their cardiovascular effects (BHF programme grant)

• The use of in vivo models to demonstrate that diesel exhaust particles promote thrombosis and worsen the effects of cardiac ischaemia (BHF programme grant)

• Controlled human exposure studies to woodsmoke and biodiesel (BHF programme grant)

• The physicochemical properties of nanoparticles that determines translocation to into the blood (Colt Foundation-funded research)

• The effectiveness of facemasks in preventing alterations in cardiovascular parameters following exposure to air pollution in Beijing (Langrish et al. 2012, “APIC-ESTEE”, NERC/MRC)

Current (2022) projects include:

• An literature review of the health effects of particulates derived from agricultural emissions (“AMPHoRA”, NIHR)

• The use of low-cost particle sensors to study the respiratory effects of air pollution in asthmatic adolescents and pregnant mothers in India (“DAPHNE”, NERC/MRC)

• A consortium network to assess potential solutions to indoor air pollution (“HEICCAM”, UKRI/NERC SPF)

• The ability of diesel exhaust particles to promote kidney injury (BHF-funded research)

• The effect of exposure to indoor and outdoor air pollution in pregnancy (“RESPIRE”, UKRI/NERC SPF)

My research also includes manufactured nanoparticles, which are rapidly being developed for applications in almost every aspect of life. These nanoparticles share some of the physicochemical properties with environmental particles, yet their potential to cause cardiovascular harm has received very little attention.

For the European Union FP7 consortium project, “NanoMILE”, we explored whether the redox properties of metal-doped cerium nanoparticles determined their ability to cause atherosclerosis and whether cross-linking of the dextran surface of SPIONs stimulated thrombosis in human blood. Recently (submitted for publication 2022) we performed the first in-human inhalation of graphene oxide to assess its potential to cause cardiorespiratory effects (“ECO-ARM”).

My research investigates the adverse health effects of air pollution. I have a particular interest in the biological mechanisms by which the nano-sized particles in vehicle exhaust, such as that from diesel vehicles, interfere with the function of the cardiovascular system (the heart, blood vessels and blood). I also have an interest in the potential of manufactured nanomaterials to affect the cardiovascular system. Our research encompasses a broad range of techniques, and specialises in in vivo models and human controlled exposure studies.