Extracellular vesicles in heart failure – A study in patients with heart failure with preserved ejection fraction or heart failure with reduced ejection fraction characteristics undergoing elective coronary artery bypass grafting

Matan, Dmitri; Mobarrez, Fariborz; Löfström, Ulrika; Corbascio, Matthias; Ekström, Mattias; Hage, Camilla; Lyngå, Patrik; Persson, Bengt; Eriksson, Maria; Linde, Cecilia; Persson, Hans; Wallén, Håkan

doi:10.3389/fcvm.2022.952974

Cited by 7 publications

(5 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various clinical studies in HF patients showed the patients with higher circulating EVs had distinct EVs from healthy individuals with enriched proteins or miRNA content that can be diagnosed as biomarkers specific to cardiac origin. 43,44 Studies also showed individuals with diabetes had significantly higher levels of EVs in their circulation with the modified levels of insulin signaling and inflammatory protein cargo that functionally alter endothelial cells. 45 Our study also attempted to address this key question of whether the circulating exosomes from TAC mice are enriched in specific cargo that can be detrimental.…”

Section: Discussionmentioning

confidence: 99%

Tipifarnib Reduces Extracellular Vesicles and Protects From Heart Failure

Mallaredy,

Roy,

Cheng

et al. 2024

Circulation Research

View full text Add to dashboard Cite

BACKGROUND: Heart failure (HF) is one of the leading causes of mortality worldwide. Extracellular vesicles, including small extracellular vesicles or exosomes, and their molecular cargo are known to modulate cell-to-cell communication during multiple cardiac diseases. However, the role of systemic extracellular vesicle biogenesis inhibition in HF models is not well documented and remains unclear. METHODS: We investigated the role of circulating exosomes during cardiac dysfunction and remodeling in a mouse transverse aortic constriction (TAC) model of HF. Importantly, we investigate the efficacy of tipifarnib, a recently identified exosome biogenesis inhibitor that targets the critical proteins (Rab27a, nSMase2 [neutral sphingomyelinase 2], and Alix [ALG-2-interacting protein X]) involved in exosome biogenesis for this mouse model of HF. In this study, 10-week-old male mice underwent TAC surgery were randomly assigned to groups with and without tipifarnib treatment (10 mg/kg 3 times/wk) and monitored for 8 weeks, and a comprehensive assessment was conducted through performed echocardiographic, histological, and biochemical studies. RESULTS: TAC significantly elevated circulating plasma exosomes and markedly increased cardiac left ventricular dysfunction, cardiac hypertrophy, and fibrosis. Furthermore, injection of plasma exosomes from TAC mice induced left ventricular dysfunction and cardiomyocyte hypertrophy in uninjured mice without TAC. On the contrary, treatment of tipifarnib in TAC mice reduced circulating exosomes to baseline and remarkably improved left ventricular functions, hypertrophy, and fibrosis. Tipifarnib treatment also drastically altered the miRNA profile of circulating post-TAC exosomes, including miR 331-5p, which was highly downregulated both in TAC circulating exosomes and in TAC cardiac tissue. Mechanistically, miR 331-5p is crucial for inhibiting the fibroblast-to-myofibroblast transition by targeting HOXC8, a critical regulator of fibrosis. Tipifarnib treatment in TAC mice upregulated the expression of miR 331-5p that acts as a potent repressor for one of the fibrotic mechanisms mediated by HOXC8. CONCLUSIONS: Our study underscores the pathological role of exosomes in HF and fibrosis in response to pressure overload. Tipifarnib-mediated inhibition of exosome biogenesis and cargo sorting may serve as a viable strategy to prevent progressive cardiac remodeling in HF.

show abstract

Section: Discussionmentioning

confidence: 99%

Tipifarnib Reduces Extracellular Vesicles and Protects From Heart Failure

Mallaredy,

Roy,

Cheng

et al. 2024

Circulation Research

View full text Add to dashboard Cite

show abstract

“…PS − -EVs have been described in several distinct pathologies including multi organ dysfunction syndrome (MODS) and sepsis [30], systemic lupus erythematous (SLE) [31,32], antiphospholipid syndrome (APS) [33,34], type 1 diabetes mellitus [35], ischaemic stroke (IS) and transient ischaemic attack (TIA) [36], familial hypercholesterolemia [11,37], sickle cell disease [38], gastric cancer [39], carotid artery stenting [40], and ageing [41]. The literature regarding alltype cEVs in cHF is generally scarce [19,28,42,43] and there is no information on PS − -EVs. We have previously studied the role of PS + -EVs released by platelets [12] and immunity cells [26] in cHF patients.…”

Section: Discussionmentioning

confidence: 99%

Red Blood Cells and Endothelium Derived Circulating Extracellular Vesicles in Health and Chronic Heart Failure: A Focus on Phosphatidylserine Dynamics in Vesiculation

Suades

Vilella-Figuerola

Padró

et al. 2023

IJMS

View full text Add to dashboard Cite

Circulating extracellular microvesicles (cEVs) are characterised by presenting surface antigens of parental cells. Since their biogenesis involves the translocation of phosphatidylserine (PS) from the inner to the outer leaflet of the plasma membrane, exposed PS has been considered as a recognition hallmark of cEVs. However, not all cEVs externalise PS. In this study, we have phenotypically and quantitatively characterised cEVs by flow cytometry, paying special attention to the proportions of PS in chronic heart failure patients (cHF; n = 119) and a reference non-HF group (n = 21). PS−-cEVs were predominantly found in both groups. Parental markers showed differential pattern depending on the PS exposure. Endothelium-derived and connexin 43-rich cEVs were mainly PS−-cEVs and significantly increased in cHF. On the contrary, platelet-derived cEVs were mostly PS+ and were increased in the non-HF group. We observed similar levels of PS+- and PS−-cEVs in non-HF subjects when analysing immune cell-derived Evs, but there was a subset-specific difference in cHF patients. Indeed, those cEVs carrying CD45+, CD29+, CD11b+, and CD15+ were mainly PS+-cEVs, while those carrying CD14+, CD3+, and CD56+ were mainly PS−-cEVs. In conclusion, endothelial and red blood cells are stressed in cHF patients, as detected by a high shedding of cEVs. Despite PS+-cEVs and PS−-cEVs representing two distinct cEV populations, their release and potential function as both biomarkers and shuttles for cell communication seem unrelated to their PS content.

show abstract

“…It has been widely documented that the number of small EVs is increased in the serum of patients with HF. The origin of these small EVs is not exclusive from the damaged myocardium, since hallmarks present on the surface of the small EVs reveal that they are also derived from ECs as well as from immune cells, contributing to the development of this syndrome, promoting the inflammatory process [315][316][317][318][319][320]. Small EVs' cargo can thus be a source of HF diagnostic biomarkers.…”

Section: Small Extracellular Vesicle Transcriptomic Analyses In Heart...mentioning

confidence: 99%

Unraveling the Signaling Dynamics of Small Extracellular Vesicles in Cardiac Diseases

Caño-Carrillo,

Castillo-Casas,

Franco

et al. 2024

Cells

View full text Add to dashboard Cite

Effective intercellular communication is essential for cellular and tissue balance maintenance and response to challenges. Cellular communication methods involve direct cell contact or the release of biological molecules to cover short and long distances. However, a recent discovery in this communication network is the involvement of extracellular vesicles that host biological contents such as proteins, nucleic acids, and lipids, influencing neighboring cells. These extracellular vesicles are found in body fluids; thus, they are considered as potential disease biomarkers. Cardiovascular diseases are significant contributors to global morbidity and mortality, encompassing conditions such as ischemic heart disease, cardiomyopathies, electrical heart diseases, and heart failure. Recent studies reveal the release of extracellular vesicles by cardiovascular cells, influencing normal cardiac function and structure. However, under pathological conditions, extracellular vesicles composition changes, contributing to the development of cardiovascular diseases. Investigating the loading of molecular cargo in these extracellular vesicles is essential for understanding their role in disease development. This review consolidates the latest insights into the role of extracellular vesicles in diagnosis and prognosis of cardiovascular diseases, exploring the potential applications of extracellular vesicles in personalized therapies, shedding light on the evolving landscape of cardiovascular medicine.

show abstract

Extracellular vesicles in heart failure – A study in patients with heart failure with preserved ejection fraction or heart failure with reduced ejection fraction characteristics undergoing elective coronary artery bypass grafting

Cited by 7 publications

References 39 publications

Tipifarnib Reduces Extracellular Vesicles and Protects From Heart Failure

Tipifarnib Reduces Extracellular Vesicles and Protects From Heart Failure

Red Blood Cells and Endothelium Derived Circulating Extracellular Vesicles in Health and Chronic Heart Failure: A Focus on Phosphatidylserine Dynamics in Vesiculation

Unraveling the Signaling Dynamics of Small Extracellular Vesicles in Cardiac Diseases

Contact Info

Product

Resources

About