Angiogenesis in Peripheral Artery Disease: Focus on Growth Factor Therapy

Lower extremity peripheral artery disease (PAD) is narrowing or occlusion of the lower extremity arteries primarily due to atherosclerosis. It is typically diagnosed in the vascular laboratory by an abnormally low ankle-brachial index (ABI) study which is the ratio of highest blood pressure in the ankle arteries (dorsalis pedis or posterior tibialis) and the highest blood pressure in the brachial arteries. The clinical manifestations of PAD range from asymptomatic disease to intermittent claudication to critical limb ischemia (CLI) depending on the degree of reduction in blood flow to the extremities. Intermittent claudication (IC) is when one experiences pain or cramping with exertion in the lower extremity that is relieved with rest. CLI is the most aggressive form of PAD presenting as rest pain or nonhealing ulcers and/or gangrene of the lower extremities, often resulting in amputation(Hirsch AT, Haskal ZJ, Hertzer NR et al. Circulation 2006;113(11): e463-e654.). PAD, particularly CLI, has a very high mortality especially due to cardiovascular causes (Hirsch AT, Haskal ZJ, Hertzer NR et al. Circulation 2006;113(11): e463-e654.). Although PAD has be underdiagnosed and underrecognized for a long time, it is now gaining significant recognition in the medical and general community as it is estimated to be present in up to 8-12 million people in USA itself and up to 20% of the population above the age of 65 years may have PAD (Diehm C, Allenberg JR, Pittrow D et al. Circulation 2009;120(21):2053-2061).