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Interview Anouk Gentier in Medicines

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Interview Anouk Gentier in Medicines Dutch Medicines Days Marysa van den Berg important in the functioning of the peptide.’ Patient material was being used to test the peptide. Gentier: ‘We get both healthy and diseased smooth muscle cells taken from pa- tients that underwent surgery for their lesions in the University Hospital of Maastricht. These cells are then cultured, put upon a plate, and incubated with a medium enriched by either calcium, phosphate or both. We then treat them with either protein S Gla, bound to an imaging agent, in various con- centrations or a negative control. Then we use a colorimetric assay to measure the num- ber of microcalcifications formed.’ Promising vesicles Not only is the protein S Gla domain capa- ble of detecting microcalcifications in the MAASTRICHT UNIVERSITY body. The peptide can also block the forma- Left: calcifying cells treated with protein S Gla peptide; right: control. tion of these ticking time bombs. ‘We see fewer microcalcifications in the treated cell cultures than in the negative control cultu- res’, says Gentier. ‘The exact mechanism of action is still unknown, but we think the A peptide against peptide binds to the phosphatidylserine resi- dues of the cell membrane of smooth mus- cle cells that are exposed to a calcifying en- vironment. Through this binding the cells atherosclerosis seem less prone to calcification.’ These findings may lead to a promising new treatment against atherosclerosis, hopes One of the leading causes of death worldwide is Gentier. She and her colleagues have ideas on how this could take shape. ‘We have yet atherosclerosis. PhD student Anouk Gentier to finalise this, but we are planning on ma- developed a peptide that can both trace and block king extracellular vesicles in which we intro- duce both protein S Gla and annexin A2. calcifications in atherosclerotic plaques. The latter protein is known to have anti-in- flammatory effects. So, we would have two ways to make atherosclerotic plaques less therosclerosis is like a dam those currently used, like in PET imaging. dangerous or even disappear.’ being built inside your arte- We have the impression that these molecules For a long time, doctors and researchers ries’, says Anouk Gentier, actually inhibit the growth the microcalcifi- have assumed that microcalcifications inside PhD student at Maastricht cations.’ an atherosclerotic plaque were stabilising University.‘A ‘This dam mostly consists of The molecule in question is a modified ver- the plaque. ‘We now know it is quite the op- cholesterol, dying cells, scar tissue and micro- sion of protein S Gla domain. Protein S is posite, thanks to better tracers to monitor calcifications. The latter is my study focus.’ an endogenous anticoagulant and the Gla the process’, says Gentier. ‘And with this domain consists of multiple amino acids cal- new endogenous tracer we can learn even Protein S led glutamic acid. ‘These glutamic acids are more, and – as a big bonus – we can even A microcalcification is like a ticking time adjusted so that they carry two carboxyl treat the condition at the same time.’ bomb. Gentier: ‘It increases the pressure the (COOH) groups. These groups seem very atherosclerotic plaque experiences. If ruptu- Anouck Gentier is participa- re occurs, there could be nasty consequen- ting in the PhD Student ces, including stroke, myocardial infarction Competition at the or necrosis of limbs. So, timely identification FIGON Dutch of these microcalcifications is essential.’ A microcalcification Medicines Days Gentier has found a way to do just that, and is like a ticking time more. ‘I am developing imaging agents that target microcalcifications even earlier than bomb 16 | October 2020.
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