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Adeno-associated viral (AAV) vector-mediated therapeutics for diabetic cardiomyopathy - current and future perspectives.

ABSTRACT: Diabetes increases the prevalence of heart failure by 6-8-fold, independent of other comorbidities such as hypertension and coronary artery disease, a phenomenon termed diabetic cardiomyopathy. Several key signalling pathways have been identified that drive the pathological changes associated with diabetes-induced heart failure. This has led to the development of multiple pharmacological agents that are currently available for clinical use. While fairly effective at delaying disease progression, these treatments do not reverse the cardiac damage associated with diabetes. One potential alternative avenue for targeting diabetes-induced heart failure is the use of adeno-associated viral vector (AAV) gene therapy, which has shown great versatility in a multitude of disease settings. AAV gene therapy has the potential to target specific cells or tissues, has a low host immune response and has the possibility to represent a lifelong cure, not possible with current conventional pharmacotherapies. In this review, we will assess the therapeutic potential of AAV gene therapy as a treatment for diabetic cardiomyopathy.

SUBMITTER: Prakoso D

PROVIDER: S-EPMC8187922 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Adeno-associated viral (AAV) vector-mediated therapeutics for diabetic cardiomyopathy - current and future perspectives.

Prakoso Darnel D Tate Mitchel M Blasio Miles J De MJ Ritchie Rebecca H RH

Clinical science (London, England : 1979) 20210601 11

Diabetes increases the prevalence of heart failure by 6-8-fold, independent of other comorbidities such as hypertension and coronary artery disease, a phenomenon termed diabetic cardiomyopathy. Several key signalling pathways have been identified that drive the pathological changes associated with diabetes-induced heart failure. This has led to the development of multiple pharmacological agents that are currently available for clinical use. While fairly effective at delaying disease progression, ...[more]

PMID: 34076247

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Project description:Diabetes mellitus and the associated complications represent a global burden on human health and economics. Cardiovascular diseases are the leading cause of death in diabetic patients, who have a 2-5 times higher risk of developing heart failure than age-matched non-diabetic patients, independent of other comorbidities. Diabetic cardiomyopathy is defined as the presence of abnormal cardiac structure and performance in the absence of other cardiac risk factors, such coronary artery disease, hypertension, and significant valvular disease. Hyperglycemia, hyperinsulinemia, and insulin resistance mediate the pathological remodeling of the heart, characterized by left ventricle concentric hypertrophy and perivascular and interstitial fibrosis leading to diastolic dysfunction. A change in the metabolic status, impaired calcium homeostasis and energy production, increased inflammation and oxidative stress, as well as an accumulation of advanced glycation end products are among the mechanisms implicated in the pathogenesis of diabetic cardiomyopathy. Despite a growing interest in the pathophysiology of diabetic cardiomyopathy, there are no specific guidelines for diagnosing patients or structuring a treatment strategy in clinical practice. Anti-hyperglycemic drugs are crucial in the management of diabetes by effectively reducing microvascular complications, preventing renal failure, retinopathy, and nerve damage. Interestingly, several drugs currently in use can improve cardiac health beyond their ability to control glycemia. GLP-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors have been shown to have a beneficial effect on the cardiovascular system through a direct effect on myocardium, beyond their ability to lower blood glucose levels. In recent years, great improvements have been made toward the possibility of modulating the expression of specific cardiac genes or non-coding RNAs in vivo for therapeutic purpose, opening up the possibility to regulate the expression of key players in the development/progression of diabetic cardiomyopathy. This review summarizes the pathogenesis of diabetic cardiomyopathy, with particular focus on structural and molecular abnormalities occurring during its progression, as well as both current and potential future therapies.

Dataset Information

Adeno-associated viral (AAV) vector-mediated therapeutics for diabetic cardiomyopathy - current and future perspectives.

Publications

Adeno-associated viral (AAV) vector-mediated therapeutics for diabetic cardiomyopathy - current and future perspectives.

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