Atorvastatin mediates increases in intralesional BAX and BAK expression in human end-stage abdominal aortic aneurysms

Morris Schweitzer, Benjamin Mitmaker, Daniel Obrand, Nathan Sheiner, Cherrie Abraham, Stevan Dostanic, Lorraine E. Chalifour

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Chronic apoptosis activation may participate in abdominal aortic aneurysm (AAA) expansion. Statin treatment slows AAA progression independent of cholesterol lowering. We hypothesized that Atorvastatin treatment alters apoptosis protein expression and activation in AAAs. Protein was isolated from the central and distal portions of end-stage human AAA tissue obtained during surgical repair from non-statin (NST) and Atorvastatin-treated (AT) patients. Expression was compared using immunoblots. Bcl-2 expression was unchanged but Bak (4-fold, p < 0.013) and Bax (3-fold, p < 0.035) expression was increased in AT (n = 12) versus NST (n = 15) patients. No cytochrome c release or caspase 3 activation was detected and Clusterin, GRP78, and BNIP1 expression was similar in NST and AT samples. Bcl-2 and Bax cDNA sequences from AAA tissue (n = 10) and the general population were identical. Thus, the increase in Bax and Bak in AT-treated AAAs did not activate the mitochondria or endoplasmic reticulum mediated apoptosis pathways. Bcl-2, Bax, and Bak have non-apoptosis related functions that include maintenance of endoplasmic reticulum (ER), homeostasis, and adaptation to stress. We speculate that Atorvastatin-mediated increases in Bax and Bak may positively affect their non-apotosis related cell functions to account for the beneficial effect of statins to slow AAA expansion.

Original languageEnglish (US)
Pages (from-to)915-922
Number of pages8
JournalCanadian Journal of Physiology and Pharmacology
Volume87
Issue number11
DOIs
StatePublished - Nov 1 2009

Keywords

  • Abdominal aortic aneurysm
  • Apoptosis
  • Atorvastatin
  • Bak
  • Bax
  • Bcl-2

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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