Adam Greenstein is a clinician scientist at the University of Manchester. At Manchester University Hospitals Foundation Trust, Adam works as a consultant physician as part of the internationally renowned Hypertension (high blood pressure) service. Adam also works as a consultant geriatrician (Care of the Elderly doctor). His clinical expertise is in diagnosis and management of hypertension, prevention of hypertension induced brain disease (vascular dementia and stroke) and in obesity-related hypertension.

At the University of Manchester and adjacent to his clinical work at the hospital, Adam runs a laboratory based basic sciences research programme investigating the diseases he sees in his day-to-day clinical practice. The laboratory seeks to understand precisely how high blood pressure damages small arteries and how this relates to the development of diseases such as Vascular Dementia or kidney disease. The group is also investigating the commonality of small artery damage shared between Alzheimer's Disease and Vascular Dementia. A second focus of his laboratory is the mechanism by which people develop high blood pressure when they put on weight, a condition called obesity-related hypertension.

Adam has published his work in all of the world's top cardiovascular journals including Circulation, Circulation Research, Hypertension and the Journal of the American College of Cardiology. He also regularly publishes in top ranked science journals such as Proceedings of the National Academy of Sciences (PNAS), The Journal of Clinical Investigation (JCI), Nature Communications and Science Signaling. Adam frequently presents work from his laboratory at international scientific and medical meetings.

Adam's research has been funded by the British Heart Foundation continuously for over 10 years and his work has featured on several promotional campaigns for them (Father's Day, Gifts and Wills - see 'Media'). In 2020, Adam's work on the mechanisms responsible for obesity related hypertension was awarded 'Best Basic Science Paper' by the American Heart Association journal 'Hypertension'. 

Dr Greenstein trained in medicine at the University of Manchester, during which he also completed an undergraduate degree in Pharmacology. After completion of junior doctor posts in Yorkshire, he trained in Hypertension at Manchester Royal Infirmary where he continues to work. His PhD investigated the interplay between adipose tissue and small resistance arteries in obesity. This was followed by a BHF Travel Fellowship on Vascular Physiology with Professor Mark Nelson at the University of Vermont. Between 2012 and 2016, he was recipient of a BHF Intermediate Clinical Research Fellowship.  

Research Projects

Hypertension and Small Vessel Disease of the Brain

Vascular dementia is the second most common form of dementia after Alzheimer's Disease and yet there is almost no understanding about how or why it develops. As a result there are no treatments and this is a devastating situation for both patients and their families. It is generally accepted that vascular dementia is caused by small vessel disease of the brain. When small brain arteries cannot function normally a process called neurovascular coupling is damaged. Neurovascular coupling is the mechanism by which neuronal activity in the brain triggers an increase in blood flow and the active brain tissue is therefore supplied with oxygen and nutrients. When small arteries are unable to perform neurovascular coupling, local brain tissue dies and characteristic 'white matter lesions' develop. Over time, this leads to a reduction in cognition.

Hypertension is by far the most important risk factor for small vessel disease of the brain. Using a variety of approaches in the laboratory (pressure myography, electrophysiology, high speed confocal microscopy) we are assessing the ways in which hypertension damages small arteries.  From a clinical perspective we hope that one day we will be able to develop a dual approach to small vessel disease of the brain: systemic treatment of hypertension in parallel with a molecularly targeted approach to restore the small artery signalling physiology. 

Obesity and Hypertension

A long standing interest in the lab is the relationship between weight and blood pressure. Obesity is without a doubt one of the world's leading health emergencies and as weight increases, blood pressure rises. There are multiple reasons why this happens but we are looking at this from the perspective of small arteries. Over the last ten years or so, we have seen that weight gain increases the contractility of small arteries. This was initially investigated by looking at fat tissue.

We investigated the vasodilating action of the adipose tissue which surrounds small arteries (PeriVascular Adipose Tissue, or PVAT). In 2009 as part of my PhD with Tony Heagerty, we published the first human small artery study of PVAT and demonstrated that the vasoactive effects are due to adiponectin release from adipocytes. I also showed that in obese patients the function of PVAT was completely lost because of adipose tissue inflammation. This observation provides a possible explanation for the development of hypertension in obesity. In 2013, we published a follow-up study in the Journal of the American College of Cardiology showing that the function of PVAT was rescued after obese patients underwent bariatric (weight reduction) surgery.

We now look at the ways in which obesity changes the signalling pathways within the vascular smooth muscle cells and the endothelium of small arteries. This approach was supported by the the BHF who helped me establish a cutting edge small artery laboratory in Manchester through an Infrastructure Grant. We were awarded funds to purchase a high speed spinning disc confocal microscope (Andor Revolution XD). This exciting state of the art technology now enables us to very accurately quantify changes to the intracellular signalling molecule Calcium within vascular smooth muscle, the endothelium and adipose tissue. 

The lab in Manchester is funded through a variety of British Heart Foundation Grants. Clinicians are funded through Clinical Training Research Fellowships. Project Grants fund post-doctoral posts and I am part of the 4 year Manchester BHF PhD Studentship programme. 

Link to my Google Scholar Citations Index

Professor Mark Nelson, University of Vermont, USA http://www.med.uvm.edu/pharmacology/WebBio.asp?SiteAreaID=663

Professor Philip Eaton, William Harvey Cardiovascular Research Group, Queen Mary University of London

• Royal College of Physicians
• British and Irish Hypertension Society (Member of Executive Committee & Education Study Group)
• International Society for Hypertension

Clinical study design and oversight (including LREC/MHRA application)

Good Clinical Practice

Pressure and wire myography (myogenic tone, agonist induced tone, structural remodeling of arteries)

High speed confocal imaging of calcium events in arteries (vascular smooth muscle cells and endothelium)

Patch clamp electrophysiology of vascular smooth muscle cells and endothelial cells
 

• BSc(Hons) Pharmacology 1994
• MB ChB 1997
• MRCP 2001
• PhD 2009