Increased plasminogen activator inhibitor type-1 (PAI-1) in the heart as a function of age
Burton E Sobel1, Yong-Ho Lee, Richard E Pratley
1University of Vermont, Cardiovascular Research Institute, Colchester Research Facility, 208 South Park Drive, Colchester, VT 05446, USA. burt.sobel@vtmednet.org
Insights
Cardiac fibrosis, a contributor to heart failure, is linked to aging and insulin resistance. This study found that heart PAI-1 (Plasminogen activator inhibitor-1) increases with age, potentially worsening fibrosis, especially with insulin resistance.
Area of Science:
- Cardiovascular Biology
- Aging Research
- Metabolic Disease
Background:
- Heart failure is linked to aging, insulin resistance, and cardiac fibrosis.
- Plasminogen activator inhibitor-1 (PAI-1) is implicated in fibrosis across various organs.
- Elevated PAI-1 levels and expression are associated with insulin resistance.
Purpose of the Study:
- To investigate if cardiac PAI-1 expression increases with age in normal and insulin-resistant mice.
- To determine the relationship between age, insulin resistance, and cardiac PAI-1 levels.
Main Methods:
- Comparison of PAI-1 levels in the hearts of 10-week-old and 20-week-old normal and insulin-resistant transgenic mice.
- Measurement of PAI-1 concentrations in plasma for comparison with cardiac levels.
Main Results:
- Cardiac PAI-1 content significantly increased by over 60% with age.
- Age-related increases in cardiac PAI-1 were disproportionately larger than plasma PAI-1 increases.
- Elevated cardiac PAI-1 was observed in both insulin-resistant and non-insulin-resistant mice.
Conclusions:
- Cardiac PAI-1 expression increases with age, independent of insulin resistance status.
- Age-related increases in cardiac PAI-1 may contribute to cardiac fibrosis and predispose to heart failure.
- The presence of insulin resistance may exacerbate age-related cardiac fibrosis and heart failure risk.
Abstract:
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.
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