PURPOSE: Pathologic remodeling of the extracellular matrix is a critical mechanism in the development and progression of abdominal aortic aneurysms (AAAs). Although angiotensin-converting enzyme (ACE) inhibitors are known to alter vascular wall remodeling in other conditions, their effects on AAAs are unknown. In this study we assessed the effect of ACE inhibitors in a rodent model of aneurysm development. METHODS: Male Wistar rats underwent transient aortic perfusion with porcine pancreatic elastase, followed by treatment with one of three ACE inhibitors (captopril [CP], lisinopril [LP], or enalapril [EP]), an angiotensin (AT)1 receptor antagonist (losartan [LOS]), or water alone (9 rats in each group). Blood pressure and aortic diameter (AD) were measured before elastase perfusion and on day 14, with an AAA defined as an increase in AD (DeltaAD) of more than 100%. The structural features of the aortic wall were examined by means of light microscopy. RESULTS: Aneurysmal dilatation consistently developed within 14 days of elastase perfusion in untreated rats, coinciding with the development of a transmural inflammatory response and destruction of the elastic media (mean DeltaAD, 223% +/- 28%). All three ACE inhibitors prevented AAA development (mean DeltaAD: CP, 67% +/- 4%; LP, 18% +/- 12%; and EP, 14% +/- 3%; each P <.05 vs controls). ACE inhibitors also attenuated the degradation of medial elastin without diminishing the inflammatory response. Surprisingly, the aneurysm-suppressing effects of ACE inhibitors were dissociated from their effects on systemic hemodynamics, and LOS had no significant effect on aneurysm development compared with untreated controls (mean DeltaAD, 186% +/- 19%). CONCLUSION: Treatment with ACE inhibitors suppresses the development of elastase-induced AAAs in the rat. Although this is associated with the preservation of medial elastin, the mechanisms underlying these effects appear to be distinct from hemodynamic alterations alone or events mediated solely by AT1 receptors. Further studies are needed to elucidate how ACE inhibitors influence aortic wall matrix remodeling during aneurysmal degeneration.
PURPOSE: Pathologic remodeling of the extracellular matrix is a critical mechanism in the development and progression of abdominal aortic aneurysms (AAAs). Although angiotensin-converting enzyme (ACE) inhibitors are known to alter vascular wall remodeling in other conditions, their effects on AAAs are unknown. In this study we assessed the effect of ACE inhibitors in a rodent model of aneurysm development. METHODS: Male Wistar rats underwent transient aortic perfusion with porcine pancreatic elastase, followed by treatment with one of three ACE inhibitors (captopril [CP], lisinopril [LP], or enalapril [EP]), an angiotensin (AT)1 receptor antagonist (losartan [LOS]), or water alone (9 rats in each group). Blood pressure and aortic diameter (AD) were measured before elastase perfusion and on day 14, with an AAA defined as an increase in AD (DeltaAD) of more than 100%. The structural features of the aortic wall were examined by means of light microscopy. RESULTS:Aneurysmal dilatation consistently developed within 14 days of elastase perfusion in untreated rats, coinciding with the development of a transmural inflammatory response and destruction of the elastic media (mean DeltaAD, 223% +/- 28%). All three ACE inhibitors prevented AAA development (mean DeltaAD: CP, 67% +/- 4%; LP, 18% +/- 12%; and EP, 14% +/- 3%; each P <.05 vs controls). ACE inhibitors also attenuated the degradation of medial elastin without diminishing the inflammatory response. Surprisingly, the aneurysm-suppressing effects of ACE inhibitors were dissociated from their effects on systemic hemodynamics, and LOS had no significant effect on aneurysm development compared with untreated controls (mean DeltaAD, 186% +/- 19%). CONCLUSION: Treatment with ACE inhibitors suppresses the development of elastase-induced AAAs in the rat. Although this is associated with the preservation of medial elastin, the mechanisms underlying these effects appear to be distinct from hemodynamic alterations alone or events mediated solely by AT1 receptors. Further studies are needed to elucidate how ACE inhibitors influence aortic wall matrix remodeling during aneurysmal degeneration.
Authors: Amanda Soler; Ian Hunter; Gregory Joseph; Rebecca Hutcheson; Brenda Hutcheson; Jenny Yang; Frank Fan Zhang; Sachindra Raj Joshi; Chastity Bradford; Katherine H Gotlinger; Rachana Maniyar; John R Falck; Spencer Proctor; Michal Laniado Schwartzman; Sachin A Gupte; Petra Rocic Journal: J Mol Cell Cardiol Date: 2018-02-08 Impact factor: 5.000
Authors: Steven J Forrester; George W Booz; Curt D Sigmund; Thomas M Coffman; Tatsuo Kawai; Victor Rizzo; Rosario Scalia; Satoru Eguchi Journal: Physiol Rev Date: 2018-07-01 Impact factor: 37.312