Development of a universal, oriented antibody immobilization method to functionalize vascular prostheses for enhanced endothelialization for potential clinical application.

Background: Thrombosis is a common cause of vascular prosthesis failure. Antibody coating of prostheses to capture circulating endothelial progenitor cells to aid endothelialization on the device surface appears a promising solution to prevent thrombus formation. Compared with random antibody immobilization, oriented antibody coating (OAC) increases antibody-antigen binding capacity and reduces antibody immunogenicity in vivo.

The Potential Role of MiRs-139-5p and -454-3p in Endoglin-Knockdown-Induced Angiogenic Dysfunction in HUVECs.

Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by aberrant angiogenesis and vascular malformations. Mutations in the transforming growth factor beta co-receptor, endoglin (), account for approximately half of known HHT cases and cause abnormal angiogenic activity in endothelial cells (ECs). To date, how ENG deficiency contributes to EC dysfunction remains to be fully understood.

Antibody functionalized intravascular devices combined with genetically engineered endothelial colony-forming cells for targeted drug delivery: A proof-of-concept study.

This study was designed to test the ability of ex vivo antibody-coated intravascular devices to capture genetically engineered pig endothelial colony-forming cells (ECFCs) as proof of concept for their potential for in vivo targeted drug delivery. Human α-calcitonin gene-related peptide (α-CGRP) was chosen as the therapeutic molecule as it is unsuitable for systemic administration due to its potent peripheral arterial vasodilatory effect and short half-life in blood, requiring local delivery to yield therapeutic benefit in a particular vascular bed. H-2Kk, a murine leukocyte surface antigen, served as the selection marker for genetically modified ECFCs.

Exploring Endothelial Colony-Forming Cells to Better Understand the Pathophysiology of Disease: An Updated Review.

Endothelial cell (EC) dysfunction has been implicated in a variety of pathological conditions. The collection of ECs from patients is typically conducted postmortem or through invasive procedures, such as surgery and interventional procedures, hampering efforts to clarify the role of ECs in disease onset and progression. In contrast, endothelial colony-forming cells (ECFCs), also termed late endothelial progenitor cells, late outgrowth endothelial cells, blood outgrowth endothelial cells, or endothelial outgrowth cells, are obtained in a minimally invasive manner, namely, by the culture of human peripheral blood mononuclear cells in endothelial growth medium.

MicroRNA-132-3p, Downregulated in Myeloid Angiogenic Cells from Hereditary Hemorrhagic Telangiectasia Patients, Is Enriched in the TGFβ and PI3K/AKT Signalling Pathways.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare, autosomal dominant genetic disorder characterized by life-threatening vascular dysplasia. Myeloid angiogenic cells (MACs), alternatively called early endothelial progenitor cells or circulating angiogenic cells, do not directly incorporate into developing blood vessels, but augment angiogenesis in a paracrine manner. MAC dysfunction has been reported in HHT.

An optimal non-viral gene transfer method for genetically modifying porcine bone marrow-derived endothelial progenitor cells for experimental therapeutics.

No currently available treatment is able to generate new contractile tissue or significantly improve cardiac function after myocardial infarction (MI), a leading cause of morbidity and mortality worldwide. Although gene transfer-enhanced endothelial progenitor cells (GTE-EPCs) show effectiveness in MI treatment in small animal models, no clinical trials using GTE-EPCs have been documented. Before the introduction of GTE-EPCs into human trials, gene-transfer-mediated augmentation of EPC function in animal models that reflect the human MI scenario should be tested.

Endoglin deficiency impairs VEGFR2 but not FGFR1 or TIE2 activation and alters VEGF-mediated cellular responses in human primary endothelial cells.

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease characterized by vascular dysplasia. Mutations of the endoglin (ENG) gene that encodes a co-receptor of the transforming growth factor β1 signaling pathway cause type I HHT. ENG is primarily expressed in endothelial cells (ECs), but its interaction with other key angiogenic pathways to control angiogenesis has not been well addressed.

Non-Coding RNAs and Hereditary Hemorrhagic Telangiectasia.

Non-coding RNAs (ncRNAs) are functional ribonucleic acid (RNA) species that include microRNAs (miRs), a class of short non-coding RNAs (∼21-25 nucleotides), and long non-coding RNAs (lncRNAs) consisting of more than 200 nucleotides. They regulate gene expression post-transcriptionally and are involved in a wide range of pathophysiological processes. Hereditary hemorrhagic telangiectasia (HHT) is a rare disorder inherited in an autosomal dominant fashion characterized by vascular dysplasia.

Cascade screening for familial hypercholesterolemia-identification of the C308Y mutation in multiple family members and relatives for the first time in mainland China.

Background: Familial hypercholesterolemia (FH), an autosomal dominant genetic disorder, is underdiagnosed and undertreated. The majority of FH cases are caused by low density lipoprotein receptor (LDL-R) gene mutations. The C308Y mutation in LDL-R results in approximately 70% loss of LDL-R activity, leading to the elevation of low density lipoprotein-cholesterol (LDL-C) and an increased risk of premature coronary heart disease (CHD).

MicroRNA signature of human blood mononuclear cells.

MicroRNAs (miRNAs) regulate a wide range of cellular processes and functions. Blood mononuclear cells (BMNCs) participate in the immune response, inflammatory reaction and angiogenesis. In 2010, a total of 157 miRNAs were quantified by RT-qPCR and a miRNA signature was determined for human peripheral BMNCs.

MicroRNA profiling of human myeloid angiogenic cells derived from peripheral blood mononuclear cells.

Human myeloid angiogenic cells (MACs), also termed early endothelial progenitor cells, play an important role in neovascularization and vascular repair. MicroRNAs (miRNAs) are a class of naturally occurring, noncoding, short (∼22 nucleotides), single-stranded RNAs that regulate gene expression post-transcriptionally. MiRNAs have been shown to regulate MAC function.

Myeloid angiogenic cells exhibit impaired migration, reduced expression of endothelial markers, and increased apoptosis in idiopathic pulmonary arterial hypertension .

Idiopathic pulmonary arterial hypertension (IPAH) is a rare and devastating condition. There is no known cure for IPAH, and current treatment options are not always effective. Autologous myeloid angiogenic cells (MACs) have been explored as a novel therapy for IPAH, but preliminary data from clinical trials show limited beneficial effects.

Decreased levels of miR-28-5p and miR-361-3p and increased levels of insulin-like growth factor 1 mRNA in mononuclear cells from patients with hereditary hemorrhagic telangiectasia .

Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disorder inherited in an autosomal dominant manner. Patients with HHT can develop vascular dysplasias called telangiectasias and arteriovenous malformations (AVMs). Our objective was to profile and characterize micro-RNAs (miRNAs), short noncoding RNAs that regulate gene expression posttranscriptionally, in HHT patient-derived peripheral blood mononuclear cells (PBMCs).

Association of Achilles tendon thickness and LDL-cholesterol levels in patients with hypercholesterolemia.

Background: Achilles tendons are the most common sites of tendon xanthomas that are commonly caused by disturbance of lipid metabolism. Achilles tendon thickening is the early characteristic of Achilles tendon xanthomas. The relationship between Achilles tendon thickness (ATT) and LDL-C levels, and risk factors of ATT in patients with hypercholesterolemia, have thus far been poorly documented.

Transcatheter Closure Versus Repeat Surgery for the Treatment of Postoperative Left-to-Right Shunts: A Single Center 15-Year Experience.

Background: Repeat surgery and the percutaneous approach (transcatheter closure (TCC)) have been used for the management of postoperative left-to-right shunts. In this study, we described our 15 years of experience in treating postoperative left-to-right shunts with these two approaches.

Methods: From February 2002 to February 2017, 50 patients with residual left-to-right shunts, following cardiac surgery, were treated using TCC or repeat surgery.

Transcatheter closure of calcified patent ductus arteriosus in older adult patients: Immediate and 12-month follow-up results.

Objective: To present our experience in transcatheter closure of calcified patent ductus arteriosus (PDA) in older adult patients, which has rarely been reported.

Patients: From 2009 to 2014, a total of 16 patients (median age 58 years) with calcified PDA underwent transcatheter closure in our center. All patients were symptomatic with major symptoms being exertional dyspnea (in 12), palpitations (in 8), and fatigue (in 5).

The Neurorepellent Slit2 Inhibits Postadhesion Stabilization of Monocytes Tethered to Vascular Endothelial Cells.

The secreted neurorepellent Slit2, acting through its transmembrane receptor, Roundabout (Robo)-1, inhibits chemotaxis of varied cell types, including leukocytes, endothelial cells, and vascular smooth muscle cells, toward diverse attractants. The role of Slit2 in regulating the steps involved in recruitment of monocytes in vascular inflammation is not well understood. In this study, we showed that Slit2 inhibited adhesion of monocytic cells to activated human endothelial cells, as well as to immobilized ICAM-1 and VCAM-1.

Circulating angiogenic cell dysfunction in patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder. Circulating angiogenic cells (CACs) play an important role in vascular repair and regeneration. This study was designed to examine the function of CACs derived from patients with HHT.

Coculture with Late, but Not Early, Human Endothelial Progenitor Cells Up Regulates IL-1 β Expression in THP-1 Monocytic Cells in a Paracrine Manner.

Endothelial progenitor cells (EPCs) have been used in clinical trials to treat ischemic heart disease. Monocyte infiltration plays an important role in inflammation, angiogenesis, and tissue repair during tissue ischemia. It is important to understand the interactions between EPCs and monocytes.

Angiographic and clinical outcomes after implantation of drug eluting stents in bifurcation lesions with crush or kissing stent technique.

Background: Long-term outcome after bifurcation stenting with drug-eluting stents (DES) for obstructive coronary artery disease is poorly understood. In this study, we report 6-9-month angiographic follow-up and long-term clinical outcomes after implantation of drug-eluting stents by crush and kissing stent technique for coronary bifurcation lesions.

Methods: Consecutive patients undergoing bifurcation stenting with DES by crush or kissing stent technique were enrolled in a prospective registry.

A direct comparison of endothelial progenitor cell dysfunction in rat metabolic syndrome and diabetes.

Objectives: Diabetes mellitus (DM) is associated with impairment of endothelial progenitor cells (EPCs), but the effects of metabolic syndrome (MS) on EPCs have been less well characterized. We hypothesized that in the presence of MS, the number and functionality of EPCs would be markedly reduced, and would be similar to DM.

Methods: Mononuclear cells were isolated from the bone-marrow (BM) and peripheral blood of lean Zucker, obese Zucker, a model of MS, and Zucker diabetic fatty rats.

Elevated circulating microRNA-210 levels in patients with hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations: a potential new biomarker.

Pulmonary arteriovenous malformations (PAVMs), which can lead to life-threatening bleeding and other complications, have been reported to occur in 30-50% of patients with hereditary hemorrhagic telangiectasia (HHT). Circulating microRNAs (miRNAs) have emerged as new biomarkers for human diseases. This study was conducted to explore circulating miRNAs as biomarkers for the screening of HHT patients with PAVMs.

Characterization of clopidogrel hypersensitivity reactions and management with oral steroids without clopidogrel discontinuation.

Objectives: The purpose of this study was to characterize clopidogrel hypersensitivity and describe its successful management with oral steroids without clopidogrel discontinuation.

Background: Hypersensitivity reactions to clopidogrel are poorly understood and present difficulty in management.

Methods: Patients diagnosed with clopidogrel hypersensitivity after percutaneous coronary intervention underwent evaluation and received oral prednisone without clopidogrel discontinuation.

Characterization of operator learning curve for transradial coronary interventions.

Background: Transradial percutaneous coronary intervention (TR-PCI) improves clinical outcomes compared to the transfemoral (TF) approach. However, inadequate training and experience has limited widespread adoption by interventional cardiologists.

Methods And Results: Clinical and procedural characteristics for TR-PCI were prospectively collected from 1999 to 2008.