Role of elastases in vascular and lung tissue destruction

Elastin is a highly inert, long-lived, protein that is required for the structural integrity and function of the vasculature and lung. Few proteinases have the capacity to degrade elastic fibers, but once perturbed, the process of elastic fiber assembly is complex and inefficient in the adult. Two major health problems associated with elastic fiber destruction are pulmonary emphysema and abdominal aortic aneurysms. These disorders are both characterized by their association with cigarette smoking followed by macrophage accumulation with expression of matrix metalloproteinases (MMPs). Use of animal models of disease and genetically engineered mutant mice have demonstrated a role for MMPs in the pathogenesis of these destructive diseases. Proteolytic elastin fragments appear to play a major role in macrophage recruitment in these chronic inflammatory disorders. In addition, macrophage MMPs may be pivotal in causing plaque rupture leading to myocardial infarction, which is followed by acute neutrophilic inflammation with further proteolytic and oxidant-mediated tissue damage.