Abstract
Cardiovascular diseases (CVDs) are responsible for enormous socio-economic impact and the highest mortality globally. The standard of care for CVDs, which includes medications and surgical interventions, in most cases, can delay but not prevent the progression of disease. Gene therapy has been considered as a potential therapy to improve the outcomes of CVDs as it targets the molecular mechanisms implicated in heart failure. Cardiac reprogramming, therapeutic angiogenesis using growth factors, antioxidant, and anti-apoptotic therapies are the modalities of cardiac gene therapy that have led to promising results in preclinical studies. Despite the benefits observed in animal studies, the attempts to translate them to humans have been inconsistent so far. Low concentration of the gene product at the target site, incomplete understanding of the molecular pathways of the disease, selected gene delivery method, difference between animal models and humans among others are probable causes of the inconsistent results in clinics. In this review, we discuss the most recent applications of the aforementioned gene therapy strategies to improve cardiac tissue regeneration in preclinical and clinical studies as well as the challenges associated with them. In addition, we consider ongoing gene therapy clinical trials focused on cardiac regeneration in CVDs.
Highlights
Cardiovascular diseases (CVDs) remain the principal cause of mortality and morbidity worldwide
The substantial health and economic burden of CVDs could be alleviated in the future with the advancement of novel therapeutic strategies that target pathogenetic mechanisms of the diseases
Gene therapy has been considered as a promising treatment option for a variety of CVDs
Summary
Cardiovascular diseases (CVDs) remain the principal cause of mortality and morbidity worldwide. Since these therapies are targeted towards the molecular cause of a specific CVD, they could hold a promising approach to cure the disease Such treatments include cell-based therapies, therapies with growth factors and other bioactive molecules, biomaterials, and others [5–8]. There were several clinical trials for gene therapy, which showed positive results in terms of safety and certain therapeutic efficiency (trials for CAD, PAD, and HF), many other randomizedcontrolled studies failed to show the benefits of gene therapy over standard treatments [9] This lack of consistent results in clinical trials can be attributed to multiple reasons including low concentration of the transferred gene or its product at the target site, incomplete knowledge of the disease mechanism and wrong gene therapy strategy, significant differences between animal models and human subjects, and others [4,9]. We consider how cardiac gene therapy can be used to enhance angiogenesis, remodel scar tissue, alleviate production of reactive oxygen species, and prevent apoptosis
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