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.
Sobel
Burton E
BE
University of Vermont, Cardiovascular Research Institute, Colchester Research Facility, 208 South Park Drive, Colchester, VT 05446, USA. burt.sobel@vtmednet.org
Lee
Yong-Ho
YH
Pratley
Richard E
RE
Schneider
David J
DJ
D000375:Aging / Q000502:physiology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D005355:Fibrosis / Q000378:metabolism; D005951:Glucose Tolerance Test; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism*; D006579:Heterozygote; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*
D001057:Apolipoproteins E; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526295:Irs1 protein, mouse; C526298:Irs2 protein, mouse; D010750:Phosphoproteins; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors