ABSTRACT
There may be several reasons for the disparate results of the reported clinical trials of angiogenesis and the results from animal models. In addition to the issues of dose, mechanism of delivery, and endpoint, the choice of patient cohort to study may have confounded the clinical trials, making positive results unattainable. Unlike animal populations, the patient population of interest has demonstrated an inability to form or recruit adequate collateral vessels prior to inclusion in the trials. In addition, the response to simple growth factor delivery may differ in the presence of diffuse atherosclerosis and endothelial dysfunction, compared with the response in experimental ischemic models.116 Also, various cardiac medications and health states, including aspirin, captopril, lovastatin, furosemide, hypercholesterolemia, smoking, diabetes and age, inhibit negatively impact on the angiogenic response.32,112,117-121 Also impacting on the generalization of the results of the clinical trials is the recognition that patients enrolled in clinical trials of angiogenesis are highly selected on the basis of anatomy, symptoms, left ventricular function, concurrent disease and motivation.
