Mechanical Myocardial Injury and Angiogenesis: An Association with Therapeutic Potential for Advanced Ischemic Coronary Artery Disease.
The healing response of tissue after mechanical injury is a highly evolved complex response that serves as a natural defense mechanism. Tissue wounds typically heal in a temporal sequence of stages. A vital phase of wound healing is the generation of loose reparative tissue that is neovascularized and rich in angiogenic substrates--that of granulation tissue formation. A therapeutic strategy that has emerged for the treatment of patients with advanced atherosclerotic ischemic coronary disease is to therapeutically manipulate the wound healing process and induce injury in the myocardium to stimulate islands of neovascularization. This paper reviews the response of tissue, particularly the myocardium, to various forms of injury. Also discussed is the emerging hypothesis of a threshold of injury (balancing adequate injury to induce neovascularizatioin versus excessive injury resulting in adjacent myocardial damage with contractile dysfunction without additional angiogenic benefit). Initial animal and human studies from our laboratory and that of collaborators, with a new method of injury-induced angiogenesis referred to as mechanical myocardial channeling, are reviewed.
Slepian
Marvin J.
MJ
Sarver Heart Center, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA. slepian@u.arizona.edu