Gene-therapeutic Strategies in Cardiovascular Disease

A special issue of Medicines (ISSN 2305-6320). This special issue belongs to the section "Cardiology and Vascular Disease".

Deadline for manuscript submissions: closed (31 March 2018) | Viewed by 10600

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Guest Editor
Department of Advanced Molecular Therapy, Graduate School of Medicine, Faculty of Medicine, Osaka University, Japan Center of Medical Innovation and Translational Research 2-2 Yamada-oka, Suita City, Osaka 565-0871, Japan
Interests: periostin regulates inflammatory disease; hypertension; gene therapy; periostin & cancer
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Special Issue Information

Dear Colleagues,

Cardiovasucular diseases remain a large health problem. Gene therapy is a potential treatment of inherited and acquired cardivascular diseases with unmet medical needs. Initially, angiogenic gene therapy was performed for ischemic disease, but almost clinical trials at phase III failed. Only hepatocye growth factor (HGF) gene therapy, for peripheral artery disease, successfully showed a prefarable effect in phase III clinical trials; however, the results were not good enough. Fibroblast growth factor (FGF)-2 with Sendai virus is also going on; though we need to wait for the results of large clinical trials. Second, gene therapy for heart failure, to enhance myocardial contractile force, is being performed. There are some candidates, such as sarcoplasmic endoplasmic reticulum Ca (CERCA2a), adenylyl cyclase 6 (AC6), stromal cell-derived factor-1 (SDF-1), or β-adrenergic receptor kinase, and phase I and II clinical trials, at least, show the safety of gene therapy. Third, direct reprograming by several gene transfers produces myocytes from cardiac fibroblasts in animal models. Myocardial regeneration by gene transfer may be a promising modality for clinical heart failure.  In addition, the development of virus vectors is progressing rapidly, and vaccine using gene transfer may be acceptable for heart failure.

In this Special Issue, we want to integrate recent advances in gene therapy for cardiovascular disease.

Assoc. Prof. Dr. Yoshiaki Taniyama
Guest Editor

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Keywords

  • heart failure

  • angiogenesis

  • gene therapy

  • vaccine

  • drug delivery

  • myocyte regeneration

  • virus vector development

Published Papers (3 papers)

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Review

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15 pages, 698 KiB  
Review
Direct Reprograming to Regenerate Myocardium and Repair Its Pacemaker and Conduction System
by Saritha Adepu, Erik F. J. Oosterwerff, Vincent M. Christoffels and Gerard J. J. Boink
Medicines 2018, 5(2), 48; https://doi.org/10.3390/medicines5020048 - 04 Jun 2018
Cited by 3 | Viewed by 3560
Abstract
The regenerative medicine field has been revolutionized by the direct conversion of one cell type to another by ectopic expression of lineage-specific transcription factors. The direct reprogramming of fibroblasts to induced cardiac myocytes (iCMs) by core cardiac transcription factors (Gata4, Mef2c, Tbx5) both [...] Read more.
The regenerative medicine field has been revolutionized by the direct conversion of one cell type to another by ectopic expression of lineage-specific transcription factors. The direct reprogramming of fibroblasts to induced cardiac myocytes (iCMs) by core cardiac transcription factors (Gata4, Mef2c, Tbx5) both in vitro and in vivo has paved the way in cardiac regeneration and repair. Several independent research groups have successfully reported the direct reprogramming of fibroblasts in injured myocardium to cardiac myocytes employing a variety of approaches that rely on transcription factors, small molecules, and micro RNAs (miRNAs). Recently, this technology has been considered for local repair of the pacemaker and the cardiac conduction system. To address this, we will first discuss the direct reprograming advancements in the setting of working myocardium regeneration, and then elaborate on how this technology can be applied to repair the cardiac pacemaker and the conduction system. Full article
(This article belongs to the Special Issue Gene-therapeutic Strategies in Cardiovascular Disease)
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12 pages, 306 KiB  
Review
Gene-Therapeutic Strategies Targeting Angiogenesis in Peripheral Artery Disease
by Fumihiro Sanada, Yoshiaki Taniyama, Jun Muratsu, Rei Otsu, Hideo Shimizu, Hiromi Rakugi and Ryuichi Morishita
Medicines 2018, 5(2), 31; https://doi.org/10.3390/medicines5020031 - 30 Mar 2018
Cited by 14 | Viewed by 3763
Abstract
The World Health Organization announced that cardiovascular disease is the number one cause of death globally, representing 31% of all global deaths. Coronary artery disease (CAD) affects approximately 5% of the US population aged 40 years and older. With an age-adjusted prevalence of [...] Read more.
The World Health Organization announced that cardiovascular disease is the number one cause of death globally, representing 31% of all global deaths. Coronary artery disease (CAD) affects approximately 5% of the US population aged 40 years and older. With an age-adjusted prevalence of approximately 12%, peripheral artery disease (PAD) affects at least 8 to 12 million Americans. Both CAD and PAD are caused by mainly atherosclerosis, the hardening and narrowing of arteries over the years by lipid deposition in the vascular bed. Despite the significant advances in interventions for revascularization and intensive medical care, patients with CAD or PAD who undergo percutaneous transluminal angioplasty have a persistent high rate of myocardial infarction, amputation, and death. Therefore, new therapeutic strategies are urgently needed for these patients. To overcome this unmet need, therapeutic angiogenesis using angiogenic growth factors has evolved in an attempt to stimulate the growth of new vasculature to compensate for tissue ischemia. After nearly 20 years of investigation, there is growing evidence of successful or unsuccessful gene therapy for ischemic heart and limb disease. This review will discuss basic and clinical data of therapeutic angiogenesis studies employing angiogenic growth factors for PAD patients and will draw conclusions on the basis of our current understanding of the biological processes of new vascularization. Full article
(This article belongs to the Special Issue Gene-therapeutic Strategies in Cardiovascular Disease)

Other

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5 pages, 586 KiB  
Case Report
Takotsubo as Initial Manifestation of Non-Myopathic Cardiomyopathy Due to the Titin Variant c.1489G > T
by Hans Keller, Ulrike Neuhold, Franz Weidinger, Edmund Gatterer, Claudia Stöllberger, Klaus Huber and Josef Finsterer
Medicines 2018, 5(3), 80; https://doi.org/10.3390/medicines5030080 - 30 Jul 2018
Cited by 5 | Viewed by 2955
Abstract
Background: Whether patients with subclinical cardiomyopathy (CMP) are more prone to experience Takotsubo syndrome (TTS) than patients without CMP, is unknown. We present a patient with TTS as the initial manifestation of a hitherto unrecognized genetic CMP. Method: case report. Results [...] Read more.
Background: Whether patients with subclinical cardiomyopathy (CMP) are more prone to experience Takotsubo syndrome (TTS) than patients without CMP, is unknown. We present a patient with TTS as the initial manifestation of a hitherto unrecognized genetic CMP. Method: case report. Results: At age 55 after the unexpected death of her father, a now 61-year-old female had developed precordial pressure. Work-up revealed moderately reduced systolic function, dyskinesia of the interventricular septum, and indications for a TTS. Coronary angiography was normal but ventriculography showed TTS. Cardiac MRI confirmed reduced systolic function and TTS. TTS resolved without treatment and sequelae. At age 57 atrial fibrillation was recorded. After deterioration of systolic function at age 59 dilated CMP was diagnosed. Despite application of levosimendan, sacubitril, valsartan, and ivabradine, complete remission could not be achieved. Upon genetic work-up by means of a gene panel, the heterozygous mutation c.1489G > T (p. E497X) in exon 9 of the titin gene was detected and made responsible for the phenotype. Neurological work-up precluded involvement of the skeletal muscles. The further course was complicated by ventricular arrhythmias, requiring implantation of an implantable cardioverter defibrillator (ICD). Conclusions: previously subclinical CMP may initially manifest as TTS. Since patients with titin CMP are at risk of developing ventricular arrhythmias and thus to experience sudden cardiac death, appropriate anti-arrhythmic therapy needs to be established. Full article
(This article belongs to the Special Issue Gene-therapeutic Strategies in Cardiovascular Disease)
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