Provided herein are compositions and methods for preventing, ameliorating, and / or reducing
tissue ischemia and / or
tissue damage due to
ischemia, increasing
blood vessel diameter,
blood flow and tissue
perfusion in the presence of
vascular disease including
peripheral vascular disease, atherosclerotic
vascular disease,
coronary artery disease,
stroke and influencing other conditions, by suppressing CD47 and / or blocking TSP1 and / or CD47 activity or interaction. Influencing the interaction of CD47-TSP1 in blood vessels allows for control of
blood vessel diameter and
blood flow, and permits modification of
blood pressure and cardiac function. Under conditions of decreased
blood flow, for instance through injury or atherosclerosis, blocking TSP1-CD47 interaction allows blood vessels to dilate and increases blood flow, tissue
perfusion and tissue survival. This in turn reduces or prevents
tissue necrosis and death. The therapeutics identified herein allow for precise regulation of blood flow to tissues and organs which need it, while substantially avoiding systemic complications. Methods and compositions described herein can be used to increase tissue survival under conditions of trauma and
surgery, as well as conditions of chronic vascular
disease. Also disclosed are methods for the treatment of elderly subjects using agents that affect TSP1 and CD47 and thereby affect tissue
perfusion. Additionally, provided herein are compositions and methods for influencing blood coagulation, allowing for controlled increased or decreased
blood clotting. Additionally, provided herein are compositions and methods for decreasing blood flow, as in the case of
cancer through mimicking the effects of TSP1 and CD47 on
blood vessel diameter and blood flow.