Angiogenesis in the adult heart.

We have studied the development of the collateral circulation in the heart in response to gradual and progressive coronary artery occlusion. When the coronary stenosis becomes critical, tissue ischemia occurs, which we believe leads to the production (and probably to release from storage sites) of tissue hormones (mitogens) that lead to mitosis of endothelial and smooth muscle cells. We have identified from hearts several known mitogens (aFGF, bFGF), non-mitogenic angiogenic factors (TGF-beta), a new anti-mitogen, and a new myocyte-derived growth factor (structures of the last two not yet elucidated). An important principle in the development of collaterals is the remodeling of pre-existing small vessels into the much larger vascular structure. To accommodate new cells old structures have to be removed by controlled proteolysis (tPA, uPA, elastase).