IN THIS MORNING’S William Harvey lecture Axel Pries will challenge basic scientists to explore the ‘black box’ of the microcirculation. ‘To my mind, the coronary microcirculation, the business end of the circulation where oxygen diffuses into cells, represents one of the contemporary frontiers in cardiology research,’ says Pries, from the Charité University of Medicine, Berlin. ‘We still know extraordinarily little about what’s going on here.’
Recent studies show that a substantial number of patients with suspected coronary artery disease examined by coronary angiography have apparently normal arteries, suggesting they suffer from microvascular disease. Such pathologies can be attributed to spasm, coagulation, micro-obstruction by leucocytes, adverse microvascular remodelling, and endothelial dysfunction among other potential mechanisms.
Although there has been an increase in clinical papers addressing the coronary microcirculation, says Pries, the amount of basic science research has declined over the past few decades. ‘What’s needed,’ he adds, ‘is a greater understanding before we can move on to develop treatments.’
Since the microcirculation lies beyond the domain of catheter investigation and intravascular imaging, much of Pries’s work has involved mathematical modelling collaborations with the mathematician Timothy Secomb from the University of Tucson. Adequate function of terminal vascular beds, they suggest, depends on exact adjustment of vessel diameters by adaptive processes. Here they believe a ‘feedback’ system operates through the conduction of electrical signals upstream along arterioles within vascular network, preventing generation of functional arterio-veneous shunts. This conduction relies on the adequate function of connexins forming gap junctions between cells in the vessel wall. ‘The system provides the arteriole with information about the capillaries it is serving,’ explains Pries.
Another focus has been the ‘endothelial surface layer’ or ‘glycocalyx’, a gel like layer around 0.5 μm thick influencing flow resistance, inflammation and permeability. Conditions such as inflammation, diabetes mellitus and hypertension, they believe, have a negative effect on this layer.
Since graduating from the University of Cologne in 1980 Pries has exclusively focused on basic science. While he does not deny there are frustrations, the rewards of the scientific life are worthwhile. ‘Scientists need to be really determined with a thick skin because it can take years to achieve breakthroughs,’ he says. ‘But each morning you’re like a pioneer exploring new territory and don’t know where your journey will take you.’
His advice to young colleagues is to ‘cherish’ the time before administration catches up. For Pries such freedom is now gone. In December 2014 he was appointed Dean of the Charité with shared responsibility for an overall budget of €1.5 billion and 13,000 staff.
To relax he spends time with his wife and two daughters and enjoys wood turning bowls. ‘In a matter of hours you create from scratch something that is beautiful and useful. It’s a refreshing antidote to the irritants of the scientific and administrative processes,’ he says.
ESC William Harvey Lecture on Basic Science 30 Aug 9:20-10:00, Regents Park – The Hub.
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