Growth Factor Therapy in Atherosclerotic Disease-Friend or Foe

Imo   E.   Hoefer; Leo      Timmers; Jan   J.   Piek

Abstract

Stimulation of neovascularization (angiogenesis, arteriogenesis) has emerged as a promising new strategy to treat patients with coronary disease. These strategies aim to improve cardiac function by ensuring myocardial perfusion and to reduce the risk of myocardial infarction. While angiogenesis describes a de-novo formation of small caliber capillary vessels, arteriogenesis leads to the outgrowth of pre-existing arterioles into large conductance collateral arteries. Inflammatory cells (e.g. monocytes), which can produce and secrete growth factors and cytokines, mediate both processes. Several trials have shown that intra-coronary infusion of growth factors or progenitor cells can improve left ventricular function after arterial occlusion. Despite these encouraging results, potential unfavorable effects on plaque progression and stability should not be neglected. Destabilization of atherosclerotic plaques leads to plaque rupture, intravascular thrombosis and tissue infarction. Increased neovascularization of the plaque (e.g. by angiogenesis) is thought to arise from the adventitial vasa vasorum, leading to an abnormal vascular development. This network of immature vessels is a viable source of invading inflammatory cells that can contribute to plaque instability. Furthermore, intra-plaque hemorrhages can lead to accumulation of erythrocyte membranes in the plaque that are rich in phospholipids and free cholesterol, promoting lesion instability through necrotic core expansion. Future angiogenic and arteriogenic approaches need to take these pitfalls into account and should focus on stimulation of vessel growth in combination with neutral or even beneficial effects on plaque formation and composition. This review discusses the delicate balance between the benefits and the drawbacks of therapeutic strategies to influence angiogenesis and arteriogenesis.

Keywords: Atherosclerosis, angiogenesis, arteriogenesis, growth factors, plaque stability

« Previous Next »