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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 19001

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Dr. Celestino Sardu

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Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 80138 Naples, Italy
Interests: clinical cardiology; myocardial infarction; cardiovascular genetics; clinical electrophysiology; molecular cardiology
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Dear Colleagues,

microRNAs (miRs) are biomarkers of cardiovascular diseases (CDVs), which have been evaluated for diagnostic approaches and monitoring the responsiveness to medical, interventional, and surgical treatments of patients with CVDs. This has led to the initiation of many clinical trials and to the development of antago-miRs and/or mimic-miRs therapies to block and/or to promote the expression of specific miRs. This Special Issue on miRs and CVDs is therefore a particularly topical addition to the field, providing up-to-date insight into delivery antago/mimic-miRs, safety-related issues, proof-of-principle in preclinical disease models, clinical trials in CVDs patients, and approval of miR therapy-based drugs.

Assoc. Prof. Celestino Sardu
Guest Editor

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Keywords

cardiovascular diseases
microRNAs
antago-microRNAs
mimic-microRNAs
diagnosis
therapy

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Related Special Issue

microRNAs as Biomarkers of Cardiovascular Diseases 2.0 in Biomedicines (2 articles)

Published Papers (6 papers)

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Research

12 pages, 1524 KiB

Open AccessArticle

Expression of miR-1-3p, miR-16-5p and miR-122-5p as Possible Risk Factors of Secondary Cardiovascular Events

by Rafał Badacz, Paweł Kleczyński, Jacek Legutko, Krzysztof Żmudka, Jacek Gacoń, Tadeusz Przewłocki and Anna Kabłak-Ziembicka

Biomedicines 2021, 9(8), 1055; https://doi.org/10.3390/biomedicines9081055 - 20 Aug 2021

Cited by 27 | Viewed by 3607

Abstract

Ischemic event in one arterial territory increases the risk of a subsequent ischemic event. Circulating microRNAs (miRs) emerge as a potential clinical tool to assess risk of subsequent atherothrombotic events such as cardiovascular death (CVD), myocardial infarction (MI) and ischemic stroke (IS). In this prospective study, we searched for athero-specific miRs related to cardiovascular event risk in patients with symptomatic coronary, carotid lesion, or both territories involvements. The choice of particular miRs was based on database research (Pub-Med, Bethesda, MD, USA) taking into consideration the relationship with development of atherosclerosis and potential prognostic value. Levels of circulating miRs (miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 and miR-499-5p) were compared in 142 patients with an acute ischemic event resulting from carotid and/or coronary artery stenosis, who underwent revascularization for symptomatic lesion. A 6-year prospective evaluation of CVD/MI/IS risk was performed. Patients with two-territory as compared to single-territory involvement differed in levels of miR-1-3p (p = 0.016), miR-16-5p (p < 0.001), miR-34a-5p (p = 0.018), miR-122-5p (p = 0.007), miR-124-3p (p < 0.001) and miR-499-5p (p < 0.001). During follow-up, 62 (43.7%) episodes of CVD/MI/IS occurred. In multivariate Cox analysis, miR-122-5p (HR = 1.0006, 95%CI = 1.0001–1.0011) and peripheral artery disease (PAD) (HR = 2.16, 95%CI = 1.26–3.70) were associated with CVD/MI/IS risk; miR-1-3p (HR = 2.73, 95%CI = 1.22–6.12) and PAD (HR = 3.47, 95%CI = 1.88–6.41) with CVD; miR-122-5p (HR = 1.0001, 95%CI = 1.000–1.0002) and creatinine level (HR = 1.02, 95%CI = 1.01–1.04) with IS, and miR-16-5p (HR = 1.0004, 95%CI = 1.0001–1.0008) with MI. Expression of miR-1-3p, miR-16-5p and miR-122-5p during incident ischemia may be possible risk factors of secondary cardiovascular event(s). Full article

(This article belongs to the Special Issue microRNAs as Biomarkers of Cardiovascular Diseases)

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17 pages, 3559 KiB

Open AccessArticle

Expression and Change of miRs 145, 221 and 222 in Hypertensive Subjects Treated with Enalapril, Losartan or Olmesartan

by Giuseppe Mandraffino, Alberto Lo Gullo, Maria Cinquegrani, Angela D’Ascola, Davide Sinicropi, Egidio Imbalzano, Giuseppe Blando, Giuseppe Maurizio Campo, Carmela Morace, Clemente Giuffrida, Salvatore Campo, Giovanni Squadrito and Michele Scuruchi

Biomedicines 2021, 9(8), 860; https://doi.org/10.3390/biomedicines9080860 - 22 Jul 2021

Cited by 5 | Viewed by 2485

Abstract

miR profile could be associated to CV risk, and also to prognosis/outcome in response to therapeutic approach. We aimed to evaluate if anti-hypertensive drugs enalapril, losartan or olmesartan have effects on monocyte miR profile in essential hypertensives without target organ involvement. For this purpose, 82 hypertensives and 49 controls were included; we evaluated SBP/DBP, lipid profile, glucose, CRP, fibrinogen, arterial stiffness indices (PWV; AIx), and cIMT at baseline (T0) and after 24 weeks of treatment (T1). Subjects with LDL-C ≥ 160 mg/dL, TG ≥ 200 mg/dL, BMI ≥ 30, and other additional CV risk factors were excluded. Patients who were prescribed to receive once-a-day enalapril 20 mg, losartan 100 mg or olmesartan 20 mg were eligible for the study. At T1, we found a significant improvement of SBP (−18.5%), DBP (−18%), HDL-C and LDL-C (+3% and −5.42%), glucose (−2.15%), BMI (−3.23%), fibrinogen (−11%), CRP (−17.5%,), AIx (−49.1%) PWV (−32.2%), and monocyte miR expression (miR-221: −28.4%; miR-222: −36%; miR-145: +41.7%) with respect to baseline. miR profile was compared to control subjects at baseline and at T1. We found some little difference in the behaviour of the three treatments on some variables: olmesartan was the most effective in reducing fibrinogen, DBP, CRP, and AIx (−13.1%, −19.3%, −21.4%, and −56.8%, respectively). Enalapril was the drug more significantly increasing the expression of miR-145. In conclusion, enalapril, losartan and olmesartan are effective in improving mechanical and humoral factors associated to AS and atherogenesis. These drugs appear to be able to modify miRs 221/222 and miR-145 expression in drug-naïve hypertensives, making it closer to that of control subjects; additionally, this provides a good blood pressure compensation, contributing to slow the progression of vascular damage. Full article

(This article belongs to the Special Issue microRNAs as Biomarkers of Cardiovascular Diseases)

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13 pages, 504 KiB

Open AccessEditor’s ChoiceArticle

Atherosclerotic Plaque Fissuration and Clinical Outcomes in Pre-Diabetics vs. Normoglycemics Patients Affected by Asymptomatic Significant Carotid Artery Stenosis at 2 Years of Follow-Up: Role of microRNAs Modulation: The ATIMIR Study

by Celestino Sardu, Pietro Modugno, Gaetano Castellano, Lucia Scisciola, Michelangela Barbieri, Lella Petrella, Mara Fanelli, Gabriella Macchia, Eugenio Caradonna, Massimo Massetti, Giuseppe Paolisso and Raffaele Marfella

Biomedicines 2021, 9(4), 401; https://doi.org/10.3390/biomedicines9040401 - 8 Apr 2021

Cited by 24 | Viewed by 3058

Abstract

Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, metformin therapy reducing the metabolic distress and the inflammatory burden could reduce MACE in ACAS patients with pre-diabetes. In this setting, the microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture, and worse prognosis in normoglycemics (NG) versus pre-diabetics metformin users (PDMU) versus pre-diabetics non-metformin users (PDNMU). However, our study aimed to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG versus PDMU versus PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. The study included 234 patients with ACAS divided into NG (n = 125), PDNMU (n = 73), and PDMU (n = 36). The miRs’ expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from the patients’ plasma samples from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG versus PDMU versus PDNMU. Prediabetics versus NG had over-inflammation (p < 0.05) and over expressed miR-24 and miR-27 at baseline. At 2 years of follow-up, PDNMU versus NG, PDMU versus NG, and PDNMU versus PDMU over-expressed inflammatory markers and miR-24, miR-27, miR-100, miR-126, and miR-133 (p < 0.05). Finally, at the end of follow-up, we observed a significant difference about MACE comparing PDNMU versus NG (n = 27 (36.9%) versus n = 8 (6.4%); p < 0.05), PDNMU versus PDMU (n = 27 (36.9%) versus n = 6 (16.6%); p < 0.05); and PDMU versus NG (n = 6 (16.6%) versus n = 8 (6.4%); p < 0.05). Admission glucose values (HR (hazard ratio) 1.020, CI (confidence of interval) 95% (1.001–1.038), p = 0.029), atheromatous carotid plaque (HR 5.373, CI 95% (1.251–11.079), p = 0.024), and miR-24 (HR 3.842, CI 95% (1.768–19.222), p = 0.011) predicted MACE at 2 years of follow-up. Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU versus PDMU after endarterectomy. MiR24, hyperglycemia, and atheromatous plaque could predict MACE at 2 years of follow-up. Full article

(This article belongs to the Special Issue microRNAs as Biomarkers of Cardiovascular Diseases)

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15 pages, 3443 KiB

Open AccessArticle

miR-30b-5p Downregulation as a Predictive Biomarker of Coronary In-Stent Restenosis

by Encarnación Gutierrez-Carretero, Isabel Mayoral-González, Francisco Jesús Morón, Mónica Fernández-Quero, Alejandro Domínguez-Rodríguez, Antonio Ordóñez and Tarik Smani

Biomedicines 2021, 9(4), 354; https://doi.org/10.3390/biomedicines9040354 - 30 Mar 2021

Cited by 5 | Viewed by 2523

Abstract

In-stent restenosis (ISR) is one of the main limitations of percutaneous coronary intervention (PCI) therapy with drug-eluting stents (DES) implantation. The aim of this study was to determine if circulating microRNAs (miRNAs) have diagnostic capability for determining ISR in a cohort of matched patients. Blood samples were collected from 55 patients who underwent previously PCI and were readmitted for a new coronary angiography. Patients were divided into subgroups comprising patients who presented ISR or not (non-ISR). A microarray analysis determined that up to 49 miRNAs were differentially expressed between ISR and non-ISR patients. Of these, 10 miRNAs are related to vascular smooth muscle and endothelial cells proliferation, migration, and differentiation, well-known hallmarks of vascular remodeling. Additionally, we identified that the expression of miR-30b-5p is significantly lower in serum samples of ISR patients, as compared to non-ISR. A further analysis demonstrated that miR-30b-5p provides better values of the receiver operator characteristic curve than other miRNAs and biochemical parameters. Finally, the in-silico analysis suggests that miR-30b-5p is predicted to target 62 genes involved in different signaling pathways involved in vascular remodeling. In conclusion, we determined for the first time that circulating mi-R30b-5p can reliably prognose restenosis in patient with implanted DES, which could be potentially helpful in the establishment of an early diagnosis and therapy of ISR. Full article

(This article belongs to the Special Issue microRNAs as Biomarkers of Cardiovascular Diseases)

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12 pages, 2520 KiB

Open AccessEditor’s ChoiceArticle

Differential Role of Circulating microRNAs to Track Progression and Pre-Symptomatic Stage of Chronic Heart Failure: A Pilot Study

by Yuri D’Alessandra, Mattia Chiesa, Maria Cristina Carena, Antonio Paolo Beltrami, Paola Rizzo, Marta Buzzetti, Veronica Ricci, Roberto Ferrari, Alessandro Fucili, Ugolino Livi, Aneta Aleksova, Giulio Pompilio and Gualtiero I. Colombo

Biomedicines 2020, 8(12), 597; https://doi.org/10.3390/biomedicines8120597 - 11 Dec 2020

Cited by 20 | Viewed by 3051

Abstract

(1)Background: Chronic heart failure (CHF) contributes to the overall burden of cardiovascular disease. Early identification of at-risk individuals may facilitate the targeting of precision therapies. Plasma microRNAs are promising circulating biomarkers for their implications with cardiac pathologies. In this pilot study, we investigate the possible exploitability of circulating micro-RNAs (miRNAs) to track chronic heart failure (CHF) occurrence, and progression from NYHA class I to IV. (2)Methods: We screened 367 microRNAs using TaqMan microRNA Arrays in plasma samples from healthy controls (HC) and CHF NYHA-class I-to-IV patients (5/group). Validation was performed by singleplex assays on 10 HC and 61 CHF subjects. Differences in the expression of validated microRNAs were evaluated through analysis of covariance (ANCOVA). Associations between N-terminal pro-BNP (NT-proBNP), left ventricular end-diastolic volume (LVEDV) or peak oxygen uptake (VO2 peak) and plasma microRNA were assessed by multivariable linear regression analysis. (3)Results: Twelve microRNAs showed higher expression in CHF patients vs. HC. Seven microRNAs were associated with NT-proBNP concentration; of these, miR-423-5p was also an independent predictor of LVEDV. Moreover, miR-499-5p was a predictor of the VO2 peak. Finally, a cluster of 5 miRNAs discriminated New York Heart Association (NYHA) class-I from HC subjects. (4)Conclusions: Our data suggest that circulating miRNAs have the potential to serve as pathophysiology-based markers of HF status and progression, and as indicators of pre-symptomatic individuals. Full article

(This article belongs to the Special Issue microRNAs as Biomarkers of Cardiovascular Diseases)

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21 pages, 2007 KiB

Open AccessArticle

Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling

by Theresa Aliwarga, Xiaoyun Guo, Eric A. Evangelista, Rozenn N. Lemaitre, Nona Sotoodehnia, Sina A. Gharib, Darryl C. Zeldin, Qinghang Liu and Rheem A. Totah

Biomedicines 2020, 8(6), 144; https://doi.org/10.3390/biomedicines8060144 - 30 May 2020

Cited by 10 | Viewed by 2929

Abstract

Elevated cis-epoxyeicosatrienoic acids (EETs) are known to be cardioprotective during ischemia-reperfusion injury in cardiomyocyte-specific overexpressing cytochrome P450 2J2 (CYP2J2) transgenic (Tr) mice. Using the same Tr mice, we measured changes in cardiac and erythrocyte membranes EETs following myocardial infarction (MI) to determine if they can serve as reporters for cardiac events. Cardiac function was also assessed in Tr vs. wild-type (WT) mice in correlation with EET changes two weeks following MI. Tr mice (N = 25, 16 female, nine male) had significantly higher cardiac cis- and trans-EETs compared to their WT counterparts (N = 25, 18 female, seven male). Total cardiac cis-EETs in Tr mice were positively correlated with total cis-EETs in erythrocyte membrane, but there was no correlation with trans-EETs or in WT mice. Following MI, cis- and trans-EETs were elevated in the erythrocyte membrane and cardiac tissue in Tr mice, accounting for the improved cardiac outcomes observed. Tr mice showed significantly better myocardial remodeling following MI, evidenced by higher % fractional shortening, smaller infarct size, lower reactive oxygen species (ROS) formation, reduced fibrosis and apoptosis, and lower pulmonary edema. A positive correlation between total cardiac cis-EETs and total erythrocyte membrane cis-EETs in a Tr mouse model suggests that erythrocyte cis-EETs may be used as predictive markers for cardiac events. All cis-EET regioisomers displayed similar trends following acute MI; however, the magnitude of change for each regioisomer was markedly different, warranting measurement of each individually. Full article

(This article belongs to the Special Issue microRNAs as Biomarkers of Cardiovascular Diseases)

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