Browsing by Author "Velasco Jimeno, Carlos"

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    Molecular magnetic resonance imaging of myeloperoxidase activity identifies culprit lesions and predicts future atherothrombosis
    (2024) Nadel, James; Wang, Xiaoying; Saha, Prakash; Bongers, André; Tumanov, Sergey; Giannotti, Nicola; Chen, Weiyu; Vigder, Niv; Chowdhury, Mohammed; Lima da Cruz, Gastao; Velasco Jimeno, Carlos; Prieto Vasquez, Claudia; Jabbour, Andrew; Botnar, Rene Michael; Stocker, Roland; Phinikaridou, Alkystis
    Aims Unstable atherosclerotic plaques have increased activity of myeloperoxidase (MPO). We examined whether molecular magnetic resonance imaging (MRI) of intraplaque MPO activity predicts future atherothrombosis in rabbits and correlates with ruptured human atheroma. Methods and results Plaque MPO activity was assessed in vivo in rabbits (n = 12) using the MPO-gadolinium (Gd) probe at 8 and 12 weeks after induction of atherosclerosis and before pharmacological triggering of atherothrombosis. Excised plaques were used to confirm MPO activity by liquid chromatography–tandem mass spectrometry (LC–MSMS) and to determine MPO distribution by histology. MPO activity was higher in plaques that caused post-trigger atherothrombosis than plaques that did not. Among the in vivo MRI metrics, the plaques’ R1 relaxation rate after administration of MPO-Gd was the best predictor of atherothrombosis. MPO activity measured in human carotid endarterectomy specimens (n = 30) by MPO-Gd–enhanced MRI was correlated with in vivo patient MRI and histological plaque phenotyping, as well as LC–MSMS. MPO-Gd retention measured as the change in R1 relaxation from baseline was significantly greater in histologic and MRI-graded American Heart Association (AHA) type VI than type III–V plaques. This association was confirmed by comparing AHA grade to MPO activity determined by LC–MSMS. Conclusion We show that elevated intraplaque MPO activity detected by molecular MRI employing MPO-Gd predicts future atherothrombosis in a rabbit model and detects ruptured human atheroma, strengthening the translational potential of this approach to prospectively detect high-risk atherosclerosis.
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    Non-invasive in vivo imaging of changes in Collagen III turnover in myocardial fibrosis
    (2024) Chaher, Nadia; Lacerda, Sara; Digilio, Giuseppe; Padovan, Sergio; Gao, Ling; Lavín, Begoña; Stefania, Rachele; Velasco Jimeno, Carlos; Cruz, Gastão; Prieto Vásquez, Claudia; Botnar, René Michael; Phinikaridou, Alkystis
    Heart failure (HF) affects 64 million people globally with enormous societal and healthcare costs. Myocardial fibrosis, characterised by changes in collagen content drives HF. Despite evidence that collagen type III (COL3) content changes during myocardial fibrosis, in vivo imaging of COL3 has not been achieved. Here, we discovered the first imaging probe that binds to COL3 with high affinity and specificity, by screening candidate peptide-based probes. Characterisation of the probe showed favourable magnetic and biodistribution properties. The probe’s potential for in vivo molecular cardiac magnetic resonance imaging was evaluated in a murine model of myocardial infarction. Using the new probe, we were able to map and quantify, previously undetectable, spatiotemporal changes in COL3 after myocardial infarction and monitor response to treatment. This innovative probe provides a promising tool to non-invasively study the unexplored roles of COL3 in cardiac fibrosis and other cardiovascular conditions marked by changes in COL3.