title: Elastin in systemic and pulmonary hypertension.
abstract: Increased elastin production and accumulation is a rapid and sensitive response to elevated vascular wall stress in both systemic and pulmonary hypertension. While initially protecting the vessel wall, these structural changes may in the longer term result in reinforcement of the hypertensive state and contribute to the persistence of the pathology of hypertension. Rapid responses apparently uncorrelated with increased elastin mRNA, at least in the case of systemic vessels, suggest novel mechanisms perhaps including increased efficiency of message translation or matrix accumulation of the protein. Investigations using in vitro organ and cell culture models have indicated a role for phospholipases and protein kinases, including protein kinase C, in stretch-induced elastin synthesis. In addition, tyrosine phosphorylation of membrane/sub-membrane/cytoskeletal sensors, including focal adhesion kinase and members of the lipocortin family, have been shown to be important in this transduction mechanism. Because its turnover is normally very slow, additional vascular elastin accumulated during hypertensive episodes, together with its consequences for the physical properties of the vessel wall, may persist long after blood pressure is restored to normal levels. Thus, recent interest has been drawn to the possibility of achieving regression of accumulated matrix elastin by promoting turnover of this protein through activation of endogenous vascular elastase and collagenase activities.
authors.affiliation: Division of Cardiovascular Research, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: F W
authors.initials: FW
authors.lastname: Keeley
authors.forename: L A
authors.initials: LA
authors.lastname: Bartoszewicz
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001808:Blood Vessels / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism; D004549:Elastin / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000378:metabolism*
chemical_list: D004549:Elastin