STIMULATION OF ARTERIAL COLLATERAL GROWTH AND LYMPHOGENESIS

摘要

Compositions and method for stimulating and controlling arteriogenesis and lymphatic vasculature by preventing and/or reducing the cellular interaction between RAF1 and AKT have been developed. The compositions include molecules that increase the bioavailability of non-phosphorylated RAF1, for example, the RAF1 Ser259 to Ala259 mutant in (RAF1 S259A), and AKT1 inhibitory molecules. Defects, disorders or diseases of insufficient blood or lymphatic vasculature are treated by administering to a patient in need thereof, a pharmaceutical composition comprising a molecule specifically blocking RAF 1- AKT crosstalk in a pharmaceutically acceptable carrier or excipient in an amount effective to enhance the growth of blood or lymphatic vasculature in the patient in need thereof, for example, in patients with advanced vascular diseases such as atherosclerosis, diabetes or other conditions associated with defective arterial development or arterial insufficiency such as advanced coronary, peripheral or cerebral artery diseases and ischemic cardiomyopathy. Compositions can be administered by injection or by controlled or sustained release devices, coating on devices or implants, microparticles, bulking agents or depots, or other techniques providing controlled or sustain release over a period of time effective to induce blood or lymphatic vasculature growth as desired.