Gene therapy for ischaemic heart disease and heart failure

Abstract

Gene therapy has been expected to become a novel treatment method since the structure of DNA was discovered in 1953. The morbidity from cardiovascular diseases remains remarkable despite the improvement of percutaneous interventions and pharmacological treatment, underlining the need for novel therapeutics. Gene therapy-mediated therapeutic angiogenesis could help those who have not gained sufficient symptom relief with traditional treatment methods. Especially patients with severe coronary artery disease and heart failure could benefit from gene therapy. Some clinical trials have reported improved myocardial perfusion and symptom relief in CAD patients, but few trials have come up with disappointing negative results. Translating preclinical success into clinical applications has encountered difficulties in successful transduction, study design, endpoint selection, and patient selection and recruitment. However, promising new methods for transducing the cells, such as retrograde delivery and cardiac-specific AAV vectors, hold great promise for myocardial gene therapy. This review introduces gene therapy for ischaemic heart disease and heart failure and discusses the current status and future developments in this field.

MicroRNAs in Cancer and Cardiovascular Disease

“…In cancer, angiogenesis allows for a tumor to grow as new vessels provide nutrients and oxygen to malignant cells [ 59 , 60 ]. In cardiovascular disease, therapeutic angiogenesis aims to provide the blood flow to the ischemic heart tissue [ 61 , 62 ]. Thus, in both diseases, angiogenesis is an important therapeutic target, although the opposite effects are observed.…”

Deciphering the Basis of Molecular Biology of Selected Cardiovascular Diseases: A View on Network Medicine

“…Gene therapy’s main goal is to help patients refractory to traditional therapies. There are several reported techniques for cardiovascular gene delivery, and these include myocardial injections, intracoronary perfusion, and epicardial painting, with each having its own advantages and disadvantages [ 122 ]. Some human and animal preclinical trials studying several angiogenic growth factors including VEGF, FGF, HGF, PDGF, and HIF have shown increased capillary growth, increased myocardial perfusion, and improved exercise capacity in participants with coronary artery disease (CAD) [ 123 , 124 , 125 , 126 ].…”

The role of lymphangiogenesis in cardiovascular diseases and heart transplantation

“…Although tissue specific AAVs can increase therapeutic transgene levels even up to one year, adenoviruses and plasmids provide only short-term transgene expression. Also, neutralizing antibodies might limit the therapeutic effect and cause a detrimental immune response [136]. Therefore, behind the gene therapeutic processes, great attention should be paid on the basic biology and fundamental aspects.…”