Jones, E.A.V. (Elizabeth A. V.)

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    Microvascular and lymphatic dysfunction in HFpEF and its associated comorbidities
    (Springer, 2020) Jones, E.A.V. (Elizabeth A. V.); Czarnowska, E. (Elzbieta); Simmonds, S. (Steven J.); Ratajska, A. (Anna); Mulder, P. (Paul); Heymans, S. (Stephane); Kuhn, A.R. (Annika R.); Bilsen, M. (Marc) van; González-Miqueo, A. (Aránzazu); Cuijpers, I. (Ilona); Brakenhielm, E. (Ebba)
    Heart failure with preserved ejection fraction (HFpEF) is a complex heterogeneous disease for which our pathophysiological understanding is still limited and specifc prevention and treatment strategies are lacking. HFpEF is characterised by diastolic dysfunction and cardiac remodelling (fbrosis, infammation, and hypertrophy). Recently, microvascular dysfunction and chronic low-grade infammation have been proposed to participate in HFpEF development. Furthermore, several recent studies demonstrated the occurrence of generalized lymphatic dysfunction in experimental models of risk factors for HFpEF, including obesity, hypercholesterolaemia, type 2 diabetes mellitus (T2DM), hypertension, and aging. Here, we review the evidence for a combined role of coronary (micro)vascular dysfunction and lymphatic vessel alterations in mediating key pathological steps in HFpEF, including reduced cardiac perfusion, chronic low-grade infammation, and myocardial oedema, and their impact on cardiac metabolic alterations (oxygen and nutrient supply/demand imbalance), fbrosis, and cardiomyocyte stifness. We focus primarily on HFpEF caused by metabolic risk factors, such as obesity, T2DM, hypertension, and aging.
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    Evaluation of miCRovascular rarefaction in vascUlar Cognitive Impairment and heArt faiLure (CRUCIAL): Study protocol for an observational study
    (2023) Jones, E.A.V. (Elizabeth A. V.); Bastarrika, G. (Gorka); Holtackers, R.J. (Robert J.); van-Dinther, M. (Maud); Backes, W. (Walter); Hughes, A.D. (Alun D.); Thornton, G.D. (George D.); Treibel, T.A. (Thomas A.); Voorter, P. H.M. (Paulien H.M.); van-Oostenbrugge, R. (Robert); Ezponda, A. (Ana); Staals, J. (Julie); Captur, G. (Gabriela); González-Miqueo, A. (Aránzazu); Bennett, J. (Jonathan)
    Introduction: Microvascular rarefaction, the functional reduction in perfused microvessels and structural reduction of microvascular density, seems to be an important mechanism in the pathophysiology of small blood vessel related disorders including vascular cognitive impairment (VCI) due to cerebral small vessel disease and heart failure with preserved ejection fraction (HFpEF). Both diseases share common risk factors including hypertension, diabetes mellitus, obesity, and ageing; in turn, these co-morbidities are associated with microvascular rarefaction. Our consortium aims to investigate novel non-invasive tools to quantify microvascular health and rarefaction in both organs, as well as surrogate biomarkers for cerebral and/or cardiac rarefaction (via sublingual capillary health, vascular density of the retina, and RNA content of circulating extracellular vesicles), and to determine whether microvascular density relates to disease severity.Methods/design: The clinical research program of CRUCIAL consists of four observational cohort studies. We aim to recruit 75 VCI patients, 60 HFpEF patients, 60 patients with severe aortic stenosis (AS) undergoing surgical aortic valve replacement as a pressure overload HFpEF model, and 200 elderly participants with mixed comorbidities to serve as controls. Data collected will include medical history, physical examination, cognitive testing, advanced brain and cardiac MRI, ECG, echocardiography, sublingual capillary health, optical coherence tomography angiography (OCTa), extracellular vesicles RNA analysis and myocardial remodelling-related serum biomarkers. The AS cohort undergoing surgery will also have myocardial biopsy for histological microvascular assessment. Discussion: CRUCIAL will examine the pathophysiological role of microvascular rarefaction in VCI and HFpEF using advanced brain and cardiac MRI techniques. Furthermore, we will investigate surrogate biomarkers for non-invasive, faster, easier, and cheaper assessment of microvascular density since these are more likely to be disseminated into widespread clinical practice. If microvascular rarefaction is an early marker of developing small vessel diseases, then measuring rarefaction may allow pre-clinical diagnosis, with implications for screening, risk stratification, and prevention. Further knowledge of the relevance of microvascular rarefaction and its underlying mechanisms may provide new avenues for research and therapeutic targets.