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Article ; Online: miRNA-346-3p/CaMKIId axis: In'DEX'ing a new pharmacological strategy for cardioprotection.

Suades, Rosa

2021 Volume 334, Page(s) 102–103

MeSH term(s)	Calcium ; Dexmedetomidine ; Humans ; MicroRNAs/genetics ; Myocardial Reperfusion Injury ; RNA, Long Noncoding
Chemical Substances	MIRN346 microRNA, human ; MicroRNAs ; RNA, Long Noncoding ; Dexmedetomidine (67VB76HONO) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-04-20
Publishing country	Netherlands
Document type	Editorial ; Comment
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2021.04.026
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Article: Platelet-released extracellular vesicles: the effects of thrombin activation

Suades, Rosa / Padró, Teresa / Vilahur, Gemma / Badimon, Lina

Cellular and molecular life sciences. 2022 Mar., v. 79, no. 3

2022

Abstract: Platelets exert fundamental roles in thrombosis, inflammation, and angiogenesis, contributing to different pathologies from cardiovascular diseases to cancer. We previously reported that platelets release extracellular vesicles (pEVs) which contribute to ...

Abstract	Platelets exert fundamental roles in thrombosis, inflammation, and angiogenesis, contributing to different pathologies from cardiovascular diseases to cancer. We previously reported that platelets release extracellular vesicles (pEVs) which contribute to thrombus formation. However, pEV composition remains poorly defined. Indeed, pEV quality and type, rather than quantity, may be relevant in intravascular cross-talk with either circulating or vascular cells. We aimed to define the phenotypic characteristics of pEVs released spontaneously and those induced by thrombin activation to better understand their role in disease dissemination. pEVs obtained from washed platelets from healthy donor blood were characterized by flow cytometry. pEVs from thrombin-activated platelets (T-pEVs) showed higher levels of P-selectin and active form of glycoprotein IIb/IIIa than baseline non-activated platelets (B-pEVs). Following mass spectrometry-based differential proteomic analysis, significant changes in the abundance of proteins secreted in T-pEVs compared to B-pEVs were found. These differential proteins were involved in coagulation, adhesion, cytoskeleton, signal transduction, metabolism, and vesicle-mediated transport. Interestingly, release of proteins relevant for cell adhesion, intrinsic pathway coagulation, and platelet activation signalling was significantly modified by thrombin stimulation. A novel pEV-associated protein (protocadherin-α4) was found to be significantly reduced in T-pEVs showing a shift towards increased expression in the membranes of activated platelets. In summary, platelet activation induced by thrombin triggers the shedding of pEVs with a complex proteomic pattern rich in procoagulant and proadhesive proteins. Crosstalk with other vascular and blood cells in a paracrine regulatory mode could extend the prothrombotic signalling as well as promote proteostasic changes in other cellular types.
Keywords	adhesion ; angiogenesis ; cell adhesion ; coagulation ; cytoskeleton ; flow cytometry ; glycoproteins ; inflammation ; mass spectrometry ; metabolism ; phenotype ; platelet activation ; proteomics ; signal transduction ; thrombin ; thrombosis
Language	English
Dates of publication	2022-03
Size	p. 190.
Publishing place	Springer International Publishing
Document type	Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-022-04222-4
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Article ; Online: Bioinformatic platforms for clinical stratification of natural history of atherosclerotic cardiovascular diseases.

Benincasa, Giuditta / Suades, Rosa / Padró, Teresa / Badimon, Lina / Napoli, Claudio

European heart journal. Cardiovascular pharmacotherapy

2023 Volume 9, Issue 8, Page(s) 758–769

Abstract: Although bioinformatic methods gained a lot of attention in the latest years, their use in real-world studies for primary and secondary prevention of atherosclerotic cardiovascular diseases (ASCVD) is still lacking. Bioinformatic resources have been ... ...

Abstract	Although bioinformatic methods gained a lot of attention in the latest years, their use in real-world studies for primary and secondary prevention of atherosclerotic cardiovascular diseases (ASCVD) is still lacking. Bioinformatic resources have been applied to thousands of individuals from the Framingham Heart Study as well as health care-associated biobanks such as the UK Biobank, the Million Veteran Program, and the CARDIoGRAMplusC4D Consortium and randomized controlled trials (i.e. ODYSSEY, FOURIER, ASPREE, and PREDIMED). These studies contributed to the development of polygenic risk scores (PRS), which emerged as novel potent genetic-oriented tools, able to calculate the individual risk of ASCVD and to predict the individual response to therapies such as statins and proprotein convertase subtilisin/kexin type 9 inhibitor. ASCVD are the first cause of death around the world including coronary heart disease (CHD), peripheral artery disease, and stroke. To achieve the goal of precision medicine and personalized therapy, advanced bioinformatic platforms are set to link clinically useful indices to heterogeneous molecular data, mainly epigenomics, transcriptomics, metabolomics, and proteomics. The DIANA study found that differential methylation of ABCA1, TCF7, PDGFA, and PRKCZ significantly discriminated patients with acute coronary syndrome from healthy subjects and their expression levels positively associated with CK-MB serum concentrations. The ARIC Study revealed several plasma proteins, acting or not in lipid metabolism, with a potential role in determining the different pleiotropic effects of statins in each subject. The implementation of molecular high-throughput studies and bioinformatic techniques into traditional cardiovascular risk prediction scores is emerging as a more accurate practice to stratify patients earlier in life and to favour timely and tailored risk reduction strategies. Of note, radiogenomics aims to combine imaging features extracted for instance by coronary computed tomography angiography and molecular biomarkers to create CHD diagnostic algorithms useful to characterize atherosclerotic lesions and myocardial abnormalities. The current view is that such platforms could be of clinical value for prevention, risk stratification, and treatment of ASCVD.
MeSH term(s)	Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/prevention & control ; Atherosclerosis/diagnosis ; Atherosclerosis/drug therapy ; Atherosclerosis/genetics ; Coronary Disease/drug therapy ; Computational Biology
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors
Language	English
Publishing date	2023-08-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2808613-2
ISSN	2055-6845 ; 2055-6837
ISSN (online)	2055-6845
ISSN	2055-6837
DOI	10.1093/ehjcvp/pvad059
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Article ; Online: Platelet-released extracellular vesicles: the effects of thrombin activation.

Suades, Rosa / Padró, Teresa / Vilahur, Gemma / Badimon, Lina

Cellular and molecular life sciences : CMLS

2022 Volume 79, Issue 3, Page(s) 190

Abstract	Platelets exert fundamental roles in thrombosis, inflammation, and angiogenesis, contributing to different pathologies from cardiovascular diseases to cancer. We previously reported that platelets release extracellular vesicles (pEVs) which contribute to thrombus formation. However, pEV composition remains poorly defined. Indeed, pEV quality and type, rather than quantity, may be relevant in intravascular cross-talk with either circulating or vascular cells. We aimed to define the phenotypic characteristics of pEVs released spontaneously and those induced by thrombin activation to better understand their role in disease dissemination. pEVs obtained from washed platelets from healthy donor blood were characterized by flow cytometry. pEVs from thrombin-activated platelets (T-pEVs) showed higher levels of P-selectin and active form of glycoprotein IIb/IIIa than baseline non-activated platelets (B-pEVs). Following mass spectrometry-based differential proteomic analysis, significant changes in the abundance of proteins secreted in T-pEVs compared to B-pEVs were found. These differential proteins were involved in coagulation, adhesion, cytoskeleton, signal transduction, metabolism, and vesicle-mediated transport. Interestingly, release of proteins relevant for cell adhesion, intrinsic pathway coagulation, and platelet activation signalling was significantly modified by thrombin stimulation. A novel pEV-associated protein (protocadherin-α4) was found to be significantly reduced in T-pEVs showing a shift towards increased expression in the membranes of activated platelets. In summary, platelet activation induced by thrombin triggers the shedding of pEVs with a complex proteomic pattern rich in procoagulant and proadhesive proteins. Crosstalk with other vascular and blood cells in a paracrine regulatory mode could extend the prothrombotic signalling as well as promote proteostasic changes in other cellular types.
MeSH term(s)	Animals ; Atherosclerosis/metabolism ; Blood Platelets/cytology ; Blood Platelets/metabolism ; Extracellular Vesicles/metabolism ; Humans ; Platelet Activation/physiology ; Proteins/analysis ; Proteins/metabolism ; Swine ; Thrombin/metabolism ; Thrombosis/metabolism
Chemical Substances	Proteins ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2022-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-022-04222-4
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Article ; Online: Red Blood Cells and Endothelium Derived Circulating Extracellular Vesicles in Health and Chronic Heart Failure: A Focus on Phosphatidylserine Dynamics in Vesiculation.

Suades, Rosa / Vilella-Figuerola, Alba / Padró, Teresa / Mirabet, Sonia / Badimon, Lina

International journal of molecular sciences

2023 Volume 24, Issue 14

Abstract: 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, ... ...

Abstract	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;
MeSH term(s)	Humans ; Phosphatidylserines/metabolism ; Erythrocytes/metabolism ; Extracellular Vesicles/metabolism ; Endothelium/metabolism ; Heart Failure
Chemical Substances	Phosphatidylserines
Language	English
Publishing date	2023-07-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241411824
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Article ; Online: Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis.

Suades, Rosa / Greco, Maria Francesca / Padró, Teresa / Badimon, Lina

Cells

2022 Volume 11, Issue 11

Abstract: Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality all over the world. Extracellular vesicles (EVs), small lipid-bilayer membrane vesicles released by most cellular types, exert pivotal and multifaceted roles in ... ...

Abstract	Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality all over the world. Extracellular vesicles (EVs), small lipid-bilayer membrane vesicles released by most cellular types, exert pivotal and multifaceted roles in physiology and disease. Emerging evidence emphasizes the importance of EVs in intercellular communication processes with key effects on cell survival, endothelial homeostasis, inflammation, neoangiogenesis, and thrombosis. This review focuses on EVs as effective signaling molecules able to both derail vascular homeostasis and induce vascular dysfunction, inflammation, plaque progression, and thrombus formation as well as drive anti-inflammation, vascular repair, and atheroprotection. We provide a comprehensive and updated summary of the role of EVs in the development or regression of atherosclerotic lesions, highlighting the link between thrombosis and inflammation. Importantly, we also critically describe their potential clinical use as disease biomarkers or therapeutic agents in atherothrombosis.
MeSH term(s)	Atherosclerosis/pathology ; Extracellular Vesicles/pathology ; Humans ; Inflammation ; Plaque, Atherosclerotic ; Thrombosis/pathology
Language	English
Publishing date	2022-06-05
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11111845
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Article ; Online: The environment, epigenetic landscape and cardiovascular risk.

Suades, Rosa / Cosentino, Francesco

Cardiovascular research

2019 Volume 115, Issue 13, Page(s) e147–e150

MeSH term(s)	Animals ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/genetics ; Environmental Exposure/adverse effects ; Epigenesis, Genetic ; Epigenome ; Epigenomics ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Humans ; Risk Assessment ; Risk Factors
Language	English
Publishing date	2019-06-20
Publishing country	England
Document type	Journal Article
ZDB-ID	80340-6
ISSN	1755-3245 ; 0008-6363
ISSN (online)	1755-3245
ISSN	0008-6363
DOI	10.1093/cvr/cvz150
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Article ; Online: miR-619-5p and cardiogenic shock in patients with ST-segment elevation myocardial infarction.

Escate, Rafael / Padró, Teresa / Suades, Rosa / Sans-Roselló, Jordi / Devaux, Yvan / Lakkisto, Päivi / Harjola, Veli-Pekka / Sionis, Alessandro / Badimon, Lina

European journal of clinical investigation

2024 , Page(s) e14186

Abstract: Background: Cardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST-segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic ... ...

Abstract	Background: Cardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST-segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic determinants in CS. Here, we investigated plasma miRNAs in relation to CS stratification in STEMI-patients. Methods: STEMI-patients (n = 49), with (CS, n = 25) and without CS (non-CS, n = 24) fulfilling inclusion criteria were included from HSCSP-cohort (Derivation-cohort). CS-miRNAs were analysed by Affymetrix-microarray and RT-PCR. Results were validated in a second cohort of CS-patients (CardShock: n = 35) with similar inclusion/exclusion criteria as the derivation cohort. In silico analysis were performed to identify potential miRNA target genes. Results: Of the 5-miRNA signature obtained from microarray analysis, miR-619-5p showed higher levels in CS than in Non-CS patients (p = .003) and discriminating power for CS by ROC (AUC: .752, p = .003). miR-619-5p directly associated with risk scores [GRACE, p = .001; CardShock, p < .001]. Furthermore, miR-619-5p showed discrimination power for death in CS. Thus, miRNA levels were significantly higher in patients with mortality outcome both in the Derivation HSCSP-cohort (p = .02; AUC: .78 ± .095) and the Validation CardShock-cohort (p = .017; AUC: .737 ± .086) By in silico analysis, miR-619-5p target genes and TNF-alpha were involved in the regulation of inflammation. miR-619-5p and TNF-alpha levels discriminated mortality outcome in CS-patients during 30-day follow-up (Validation-Cohort: ROC: .812, p = .002; HR: 9.99, p = .003). Conclusions: Up-regulation of miR-619-5p is found in the plasma of STEMI-patients with CS and mortality outcome. These findings highlight the specificity of epigenetic regulation of inflammation on the disease severity of MI.
Language	English
Publishing date	2024-02-20
Publishing country	England
Document type	Journal Article
ZDB-ID	186196-7
ISSN	1365-2362 ; 0014-2972 ; 0960-135X
ISSN (online)	1365-2362
ISSN	0014-2972 ; 0960-135X
DOI	10.1111/eci.14186
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Article ; Online: Extracellular vesicles in atherothrombosis: From biomarkers and precision medicine to therapeutic targets

Badimon, Lina / Padro, Teresa / Arderiu, Gemma / Vilahur, Gemma / Borrell‐Pages, Maria / Suades, Rosa

Immunological Reviews 2022 Nov., v. 312, no. 1, p. 6-19

2022 , Page(s) 6–19

Abstract: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of global mortality. Extracellular vesicles (EVs) are small phospholipid vesicles that convey molecular bioactive cargoes and play essential roles in intercellular communication and, ...

Abstract	Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of global mortality. Extracellular vesicles (EVs) are small phospholipid vesicles that convey molecular bioactive cargoes and play essential roles in intercellular communication and, hence, a multifaceted role in health and disease. The present review offers a glimpse into the current state and up‐to‐date concepts on EV field. It also covers their association with several cardiovascular risk factors and ischemic conditions, being subclinical atherosclerosis of utmost relevance for prevention. Interestingly, we show that EVs hold promise as prognostic and diagnostic as well as predictive markers of ASCVD in the precision medicine era. We then report on the role of EVs in atherothrombosis, disentangling the mechanisms involved in the initiation, progression, and complication of atherosclerosis and showing their direct effect in the context of arterial thrombosis. Finally, their potential use for therapeutic intervention is highlighted.
Keywords	atherosclerosis ; biomarkers ; cell communication ; mortality ; phospholipids ; precision medicine ; risk ; thrombosis
Language	English
Dates of publication	2022-11
Size	p. 6-19.
Publishing place	John Wiley & Sons, Inc
Document type	Article ; Online
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.13127
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Article ; Online: Sirtuin 1/soluble guanylyl cyclase: a nitric oxide-independent pathway to rescue ageing-induced vascular dysfunction.

Suades, Rosa / Cosentino, Francesco

Cardiovascular research

2018 Volume 115, Issue 3, Page(s) 485–487

MeSH term(s)	Guanylate Cyclase ; Myocytes, Smooth Muscle ; Nitric Oxide ; Sirtuin 1 ; Soluble Guanylyl Cyclase ; Vasodilator Agents
Chemical Substances	Vasodilator Agents ; Nitric Oxide (31C4KY9ESH) ; Sirtuin 1 (EC 3.5.1.-) ; Guanylate Cyclase (EC 4.6.1.2) ; Soluble Guanylyl Cyclase (EC 4.6.1.2)
Language	English
Publishing date	2018-11-29
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80340-6
ISSN	1755-3245 ; 0008-6363
ISSN (online)	1755-3245
ISSN	0008-6363
DOI	10.1093/cvr/cvy297
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