Granzymes in age-related cardiovascular and pulmonary diseases

Chronic inflammation is a hallmark of age-related cardiovascular and pulmonary diseases. Granzymes are a family of serineproteasesthathavebeentraditionallyviewedasinitiatorsofimmune-mediatedcelldeath.However,recentfindingssuggestthatthe pathophysiological role of granzymes is complex. Emerging functions for granzymes in extracellular matrix degradation,autoimmunity, and inflammation suggests a multifactorial mechanism by which these enzymes are capable of mediating tissuedamage.Recentdiscoveriesshowingthatgranzymescanbeproducedandsecretedbynonimmunecellsduringdiseaseprovidean additional layer of intricacy. This review examines the emerging biochemical and clinical evidence pertaining to intracellularand/or extracellular granzymes in the pathogenesis of aging and cardiopulmonary diseases.Cell Death and Differentiation (2010) 17, 596–606; doi:10.1038/cdd.2010.5; published online 5 February 2010