Injured Cardiac Tissue-Targeted Delivery of TGFβ1 siRNA by FAP Aptamer-Functionalized Extracellular Vesicles Promotes Cardiac Repair.

Purpose: Small-interfering RNA (siRNA) therapy holds significant potential for treating cardiac injury; however, its clinical application is constrained by poor blood stability and insufficient cellular uptake. Extracellular vesicles (EVs) have emerged as an effective delivery system for siRNA in vivo; but their lack of specific cell or tissue-targeting ability remains a major challenge. Thus, we aimed to develop an EV-based delivery system capable of targeted delivery of therapeutic siRNA to injured cardiac tissue for cardiac repair.

Establishment of a human-induced pluripotent stem cell line from a long QT syndrome type 2 patient harboring a KCNH2 mutation.

Long QT syndrome type 2 (LQT2) is a heart disorder resulting from a loss-of-function mutation in theKCNH2gene that causes loss of Kv11.1 channel function, potentially resulting in syncope, arrhythmias, and sudden death. We derived induced pluripotent stem cell line from PBMC of LQT2 patient carrying a variant of pathogenic variant (c.

Small extracellular vesicle-mediated CRISPR-Cas9 RNP delivery for cardiac-specific genome editing.

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Although clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) gene editing holds immense potential for genetic manipulation, its clinical application is hindered by the absence of an efficient heart-targeted drug delivery system. Herein, we developed CRISPR-Cas9 ribonucleoprotein (RNP)-loaded extracellular vesicles (EVs) conjugated with cardiac-targeting peptide (T) for precise cardiac-specific genome editing.

Engineered small extracellular vesicle-mediated NOX4 siRNA delivery for targeted therapy of cardiac hypertrophy.

Small-interfering RNA (siRNA) therapy is considered a powerful therapeutic strategy for treating cardiac hypertrophy, an important risk factor for subsequent cardiac morbidity and mortality. However, the lack of safe and efficient in vivo delivery of siRNAs is a major challenge for broadening its clinical applications. Small extracellular vesicles (sEVs) are a promising delivery system for siRNAs but have limited cell/tissue-specific targeting ability.

Generation of two PITX2 knock-out human induced pluripotent stem cell lines using CRISPR/Cas9 system.

PITX2 is a homeobox gene located in the human 4q25 locus and is commonly associated with atrial fibrillation (AF). Here, we generated two PITX2 knock-out human induced pluripotent stem cell (iPSC) lines using CRISPR/Cas9 genome editing. The edited iPSCs maintained fullpluripotency, normal karyotype and spontaneousdifferentiation capability.

Generation of three TTN knock-out human induced pluripotent stem cell lines using CRISPR/Cas9 system.

TTN mutations are the common genetic cause for various types of cardiomyopathies (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy) and skeletal myopathies.

Generation of a heterozygous TPM1-E192K knock-in human induced pluripotent stem cell line using CRISPR/Cas9 system.

E192K missense mutation of TPM1 has been found in different types of cardiomyopathies (e.g., hypertrophic cardiomyopathy, dilated cardiomyopathy, and left ventricular non-compaction), leading to systolic dysfunction, diastolic dysfunction, and/or tachyarrhythmias.

Serum exosomal long noncoding RNAs as a diagnostic biomarker for atrial fibrillation.

Background: Exosomal long noncoding RNAs (lncRNAs) are known as ideal diagnostic biomarkers of various diseases. However, there are no reports on the use of serum exosomal lncRNAs as diagnostic biomarkers for atrial fibrillation (AF).

Objective: The purpose of this study was to explore serum exosomal lncRNAs as a useful tool for diagnosing AF.

Small extracellular vesicles derived from patients with persistent atrial fibrillation exacerbate arrhythmogenesis via miR-30a-5p.

Small extracellular vesicles (sEVs) are nanometer-sized membranous vesicles that contribute to the pathogenesis of atrial fibrillation (AF). Here, we investigated the role of sEVs derived from patients with persistent AF in the pathophysiology of AF. First, we evaluated the pathological effects of sEVs derived from the peripheral blood of patients with persistent AF (AF-sEVs).

Improved cardiac-specific delivery of RAGE siRNA within small extracellular vesicles engineered to express intense cardiac targeting peptide attenuates myocarditis.

Small extracellular vesicles (sEVs) are nanometer-sized membranous vesicles secreted by cells, with important roles in physiological and pathological processes. Recent research has established the application of sEVs as therapeutic vehicles in various conditions, including heart disease. However, the high risk of off-target effects is a major barrier for their introduction into the clinic.

High Level of Real Urban Air Pollution Promotes Cardiac Arrhythmia in Healthy Mice.

Background And Objectives: Ambient particulate matter (PM) in real urban air pollution (RUA) is an environmental health risk factor associated with increased cardiac events. This study investigated the threshold level to induce arrhythmia, as well as arrhythmogenic mechanism of RUA that mainly consisted of PM <2.5 μm in aerodynamic diameter close to ultrafine particles.

Co-delivery of curcumin and miRNA-144-3p using heart-targeted extracellular vesicles enhances the therapeutic efficacy for myocardial infarction.

Curcumin exerts therapeutic effects in heart disease, but has limited bioavailability. Extracellular vesicles (EVs) have gained attention as nanovehicles; however, the poor targeting ability of systemically administered EVs still remains a crucial issue. Herein, we generated heart-targeted EVs (CTP-EVs) by functionalizing EVs surface with cardiac targeting peptide (CTP) using genetic modification of EVs-secreting cells, and further loaded curcumin into CTP-EVs (CTP-EVs-Cur).

Therapeutic potential of miR-21 regulation by human peripheral blood derived-small extracellular vesicles in myocardial infarction.

Small extracellular vesicles (sEVs) as natural membranous vesicles are on the frontiers of nanomedical research, due to their ability to deliver therapeutic molecules such as microRNAs (miRNAs). The miRNA-21 (miR-21) is thought to be involved in the initiation and development of myocardial infarction (MI). Here, we examined whether miR-21 regulation using human peripheral blood-derived sEVs (PB-sEVs) could serve as a potential therapeutic strategy for MI.

Calcium chloride enhances the delivery of exosomes.

Exosomes might have an unimproved potential to serve as effective delivery vehicles. However, when exosomes are developed for therapeutic applications, a method to enhance their delivery is important. This study aimed to evaluate wheather calcium chloride (CaCl2) or other chloride compounds could enhance exosome delivery to various cells without causing toxicity.

[Corrigendum] Human peripheral blood‑derived exosomes for microRNA delivery.

Exosomes serve important functions in cell‑to‑cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood‑derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR‑21 using a human peripheral blood derived‑exosome may influence the degree of remodeling following myocardial infarction (MI).

Human peripheral blood‑derived exosomes for microRNA delivery.

Exosomes serve important functions in cell‑to‑cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood‑derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR‑21 using a human peripheral blood derived‑exosome may influence the degree of remodeling following myocardial infarction (MI).

Expression of miRNAs in circulating exosomes derived from patients with persistent atrial fibrillation.

Atrial fibrillation (AF), the most common type of cardiac arrhythmia, is thought to be regulated by changes in microRNA (miRNA) expression. However, the evidence for this is inconsistent. The high stability and expression of circulating exosomal miRNAs may allow their use as candidate biomarkers.

Extracellular Vesicles Derived from Hypoxic Human Mesenchymal Stem Cells Attenuate GSK3β Expression via miRNA-26a in an Ischemia-Reperfusion Injury Model.

Purpose: Bioactive molecules critical to intracellular signaling are contained in extracellular vesicles (EVs) and have cardioprotective effects in ischemia/reperfusion (IR) injured hearts. This study investigated the mechanism of the cardioprotective effects of EVs derived from hypoxia-preconditioned human mesenchymal stem cells (MSCs).

Materials And Methods: EV solutions (0.

Cardiac-specific delivery by cardiac tissue-targeting peptide-expressing exosomes.

Naturally occurring RNA carriers such as exosomes might be an untapped source of effective delivery vehicles. However, if exosomes are to be exploited for therapeutic applications, they must target specific tissues or cell types to avoid off-target effects. This study evaluated whether genetic modification of exosomes could enhance exosome delivery to heart cells and heart tissue without toxicity.

The Role of Serotonin in Ventricular Repolarization in Pregnant Mice.

Purpose: The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy.

Sympathetic nerve blocks promote anti-inflammatory response by activating the JAK2-STAT3-mediated signaling cascade in rat myocarditis models: A novel mechanism with clinical implications.

Background: Left stellectomy has become an important therapeutic option for patients with potentially fatal arrhythmias. However, the antiarrhythmic mechanism of left stellectomy is not well known. The cholinergic anti-inflammatory pathway (CAIP) is a complex immune mechanism that regulates peripheral inflammatory responses.