Extracellular Vesicle cystatin c is associated with unstable angina in troponin negative patients with acute chest pain

Dekker, Mirthe; Waissi, Farahnaz; Bennekom, Joëlle van; Silvis, Max J. M.; Timmerman, Nathalie; Schoneveld, Arjan H.; Grobbee, Diederick E.; Winter, Robbert J. de; Mosterd, Arend; Timmers, Leo; Kleijn, Dominique P. V. de

doi:10.1371/journal.pone.0237036

Cited by 9 publications

(5 citation statements)

References 40 publications

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“…For this, two EV subpopulations were isolated. The isolation was performed as described in previous publications 30 , 31 . In brief, a subset of EVs co-precipitate with low-density lipid particles (LDL) which allows separation.…”

Section: Methodsmentioning

confidence: 99%

High levels of osteoprotegerin are associated with coronary artery calcification in patients suspected of a chronic coronary syndrome

Dekker

Waissi

Silvis

et al. 2021

Sci Rep

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Plasma osteoprotegerin (OPG) and vascular smooth muscle cell (VSMC) derived extracellular vesicles (EVs) are important regulators in the process of vascular calcification (VC). In population studies, high levels of OPG are associated with events. In animal studies, however, high OPG levels result in reduction of VC. VSMC-derived EVs are assumed to be responsible for OPG transport and VC but this role has not been studied. For this, we investigated the association between OPG in plasma and circulating EVs with coronary artery calcium (CAC) as surrogate for VC in symptomatic patients. We retrospectively assessed 742 patients undergoing myocardial perfusion imaging (MPI). CAC scores were determined on the MPI-CT images using a previously developed automated algorithm. Levels of OPG were quantified in plasma and two EV-subpopulations (LDL and TEX), using an electrochemiluminescence immunoassay. Circulating levels of OPG were independently associated with CAC scores in plasma; OR 1.39 (95% CI 1.17–1.65), and both EV populations; EV-LDL; OR 1.51 (95% CI 1.27–1.80) and EV-TEX; OR 1.21 (95% CI 1.02–1.42). High levels of OPG in plasma were independently associated with CAC scores in this symptomatic patient cohort. High levels of EV-derived OPG showed the same positive association with CAC scores, suggesting that EV-derived OPG mirrors the same pathophysiological process as plasma OPG.

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Section: Methodsmentioning

confidence: 99%

High levels of osteoprotegerin are associated with coronary artery calcification in patients suspected of a chronic coronary syndrome

Dekker

Waissi

Silvis

et al. 2021

Sci Rep

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“…A different study found an independent association between the extent of CVD and the levels of EV-CD14 [111]. Several other studies investigated the role of EV content in ACS, heart failure, unstable angina and manifest CVD [112][113][114].…”

Section: Extracellular Vesicle Contentmentioning

confidence: 98%

Extracellular Vesicles in Diagnosing Chronic Coronary Syndromes the Bumpy Road to Clinical Implementation

Dekker

Waissi

Timmerman

et al. 2020

IJMS

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Coronary artery disease (CAD), comprising both acute coronary syndromes (ACS) and chronic coronary syndromes (CCS), remains one of the most important killers throughout the entire world. ACS is often quickly diagnosed by either deviation on an electrocardiogram or elevated levels of troponin, but CCS appears to be more complicated. The most used noninvasive strategies to diagnose CCS are coronary computed tomography and perfusion imaging. Although both show reasonable accuracy (80–90%), these modalities are becoming more and more subject of debate due to costs, radiation and increasing inappropriate use in low-risk patients. A reliable, blood-based biomarker is not available for CCS but would be of great clinical importance. Extracellular vesicles (EVs) are lipid-bilayer membrane vesicles containing bioactive contents e.g., proteins, lipids and nucleic acids. EVs are often referred to as the “liquid biopsy” since their contents reflect changes in the condition of the cell they originate from. Although EVs are studied extensively for their role as biomarkers in the cardiovascular field during the last decade, they are still not incorporated into clinical practice in this field. This review provides an overview on EV biomarkers in CCS and discusses the clinical and technological aspects important for successful clinical application of EVs.

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“…In CVD pathologies, alterations in circulating EV enumeration 212 and composition (miRNAs, 213,214 circular RNAs, 215 proteins [216][217][218][219] ) are also reflected in biofluids such as blood and have prognostic value in predicting cardiovascular events, 213 assessing cardiac damage, 214,215 early detections of acute coronary syndromes, 217 risk stratification of patients with unstable angina, 218 predicting cardiovascular risk via obesityinduced metabolic complications, 219 and heart failure. 216 Moreover, with the progression of CVDs, injured cells continue to secrete disease-specific EVs 212,220 that reflect cardiac damage, information that can be leveraged as diagnostic biomarkers for CVDs, guide disease-specific therapeutics, and gauge therapeutic responses.…”

Section: Diagnostic and Prognostic Potential Of Evs For Cvd Managementmentioning

confidence: 99%

The Discovery of Extracellular Vesicles and Their Emergence as a Next-Generation Therapy

Rai,

Claridge,

Lozano

et al. 2024

Circulation Research

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From their humble discovery as cellular debris to cementing their natural capacity to transfer functional molecules between cells, the long-winded journey of extracellular vesicles (EVs) now stands at the precipice as a next-generation cell-free therapeutic tool to revolutionize modern-day medicine. This perspective provides a snapshot of the discovery of EVs to their emergence as a vibrant field of biology and the renaissance they usher in the field of biomedical sciences as therapeutic agents for cardiovascular pathologies. Rapid development of bioengineered EVs is providing innovative opportunities to overcome biological challenges of natural EVs such as potency, cargo loading and enhanced secretion, targeting and circulation half-life, localized and sustained delivery strategies, approaches to enhance systemic circulation, uptake and lysosomal escape, and logistical hurdles encompassing scalability, cost, and time. A multidisciplinary collaboration beyond the field of biology now extends to chemistry, physics, biomaterials, and nanotechnology, allowing rapid development of designer therapeutic EVs that are now entering late-stage human clinical trials.

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Extracellular Vesicle cystatin c is associated with unstable angina in troponin negative patients with acute chest pain

Cited by 9 publications

References 40 publications

High levels of osteoprotegerin are associated with coronary artery calcification in patients suspected of a chronic coronary syndrome

High levels of osteoprotegerin are associated with coronary artery calcification in patients suspected of a chronic coronary syndrome

Extracellular Vesicles in Diagnosing Chronic Coronary Syndromes the Bumpy Road to Clinical Implementation

The Discovery of Extracellular Vesicles and Their Emergence as a Next-Generation Therapy

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