Increased plasminogen activator inhibitor type-1 (PAI-1) in the heart as a function of age

Heart failure is associated with advanced age and insulin resistance and is thought to be exacerbated by cardiac fibrosis. Plasminogen activator inhibitor type-1 (PAI-1) has been strongly implicated as a determinant of fibrosis in diverse organs and tissues. Its concentration is increased in blood, and its expression is increased in vessel walls in association with insulin resistance. Accordingly, we sought to determine whether expression of PAI-1 in the heart increases as a function of age of 10 week old and 20 week old normal and insulin resistant transgenic mice thereby potentially predisposing to heart failure. Results obtained indicate that PAI-1 content increases significantly in the heart as a function of age by more than 60%. The increases are much greater than those that can be accounted for by the modest, and statistically insignificant increases in the concentrations of PAI-1 in plasma that were observed to occur as a function of age as well. Thus, PAI-1 increases in the heart is a function of age, occurs in insulin resistant and non-insulin resistant mice, and may contribute to fibrosis predisposing to heart failure associated with advanced age, particularly when insulin resistance is present. (c) 2006 Elsevier Inc. All rights reserved.