Gene and cell therapy for heart disease.
Heart disease is the most common cause of morbidity and mortality in Western society and the incidence is projected to increase significantly over the next few decades as our population ages. Heart failure occurs when the heart is unable to pump blood at a rate to commensurate with tissue metabolic requirements and represents the end stage of a variety of pathological conditions. Causes of heart failure include ischemia, hypertension, coronary artery disease, and idiopathic dilated cardiomyopathy. Hypertension and ischemia both cause infarction with loss of function and a consequent contractile deficit that promotes ventricular remodeling. Remodeling results in dramatic alterations in the size, shape, and composition of the walls and chambers of the heart and can have both positive and negative effects on function. In 30-40% of patients with heart failure, left ventricular systolic function is relatively unaffected while diastolic dysfunction predominates. Recent progress in our understanding of the molecular and cellular bases of heart disease has provided new therapeutic targets and led to novel approaches including the delivery of proteins, genes, and cells to replace defective or deficient components and restore function to the diseased heart. This review focuses on three such strategies that are currently under development: (a) gene transfer to modulate contractility, (b) therapeutic angiogenesis for the treatment of ischemia, and (c) embryonic and adult stem cell transfer to replace damaged myocardium.
Graham
Regina M
RM
Department of Molecular and Cellular Pharmacology, University of Miami Medical Center, Florida 33136, USA.
Bishopric
Nanette H
NH
Webster
Keith A
KA
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006331:Heart Diseases / Q000628:therapy*; D006801:Humans; D006973:Hypertension / Q000150:complications; D008954:Models, Biological; D017202:Myocardial Ischemia / Q000150:complications / Q000209:etiology / Q000628:therapy; D018919:Neovascularization, Physiologic; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D033581:Stem Cell Transplantation; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D011943:Receptors, Adrenergic, beta; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban