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Related Experiment Videos

Regression of sclerosis in aging by an angiotensin inhibition-induced decrease in PAI-1.

L J Ma1, S Nakamura, J S Whitsitt

  • 1Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2561, USA.

Kidney International
|December 15, 2000
PubMed
Summary
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Angiotensin receptor blockers (ARBs) can reverse age-related kidney and vascular damage by reducing sclerosis and inhibiting plasminogen activator inhibitor-1 (PAI-1). This study shows ARBs promote regression of age-related sclerosis.

Area of Science:

  • Gerontology and Regenerative Medicine
  • Cardiovascular and Renal Physiology
  • Molecular Biology and Pharmacology

Background:

  • Aging is associated with increased glomerular and vascular sclerosis.
  • Angiotensin inhibitors are known to slow the progression of age-related kidney injury.
  • The potential for reversing existing sclerosis and the role of angiotensin type 1 receptor antagonists (AIIRAs) in this process require further investigation.

Purpose of the Study:

  • To investigate the potential for regression of age-related sclerosis using an AIIRA.
  • To elucidate the mechanisms by which AIIRAs may influence sclerosis remodeling.
  • To focus on plasminogen activator inhibitor-1 (PAI-1) as a key mediator due to its induction by angiotensin and inhibition of matrix degradation.

Main Methods:

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  • Male Sprague-Dawley rats (18 months old) were treated with the AIIRA losartan.
  • Animals were sacrificed at 21 and 24 months for comparison with age-matched controls.
  • Analyses included monitoring blood pressure and renal function, along with morphological, biochemical, and molecular assessments of aorta and kidney tissues.

Main Results:

  • AIIRA treatment significantly reduced aorta wall thickness and proteinuria compared to controls.
  • Glomerulosclerosis was decreased by AIIRA to levels below the initial baseline.
  • AIIRA reduced renal collagen content, tubular/interstitial cell apoptosis, and kidney PAI-1 mRNA and protein expression.

Conclusions:

  • AIIRA not only slows but also induces regression of age-related glomerular and vascular sclerosis.
  • Mechanisms involve modulation of cortical cell turnover and inhibition of PAI-1 expression.
  • These findings highlight the therapeutic potential of AIIRAs in combating age-related sclerosis.