Journal Article

ACE Inhibitors Potently Reduce Vascular Inflammation, Results of an Open Proof-Of-Concept Study in the Abdominal Aortic Aneurysm

Meijer, C. Arnoud, Hamming, Jaap F., Kortekaas, Kim E., Xu, Baohui, Hinnen, Jan Willem, Dalman, Ronald L., Lindeman, Jan H.

2014

Overview

Independent of their blood pressure lowering effect, ACE inhibitors are thought to reduce vascular inflammation. The clinical relevance of this effect is unclear with the current knowledge. Abdominal aortic aneurysms (AAA) are characterized by a broad, non-specific inflammatory response, and thus provide a clinical platform to evaluate the anti-inflammatory potential of ACE inhibitors. Eleven patients scheduled for open AAA repair received ramipril (5 mg/day) during 2-4 weeks preceding surgery. Aortic wall samples were collected during surgery, and compared to matched samples obtained from a biobank. An anti-inflammatory potential was evaluated in a comprehensive analysis that included immunohistochemistry, mRNA and protein analysis. A putative effect of ACE inhibitors on AAA growth was tested separately by comparing 18-month growth rate of patients on ACE inhibitors (n = 82) and those not taking ACE inhibitors (n = 204). Ramipril reduces mRNA expression of multiple pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, TNF -α, Interferon-[Formula: see text], and MCP-1, as well as aortic wall IL-8 and MCP-1 (P = 0.017 and 0.008, respectively) protein content. The is followed by clear effects on cell activation that included a shift towards anti-inflammatory macrophage (M2) subtype. Evaluation of data from the PHAST cohort did not indicate an effect of ACE inhibitors on 18-month aneurysm progression (mean difference at 18 months: -0.24 mm (95% CI: -0.90-0.45, P = NS). ACE inhibition quenches multiple aspects of vascular inflammation in AAA. However, this does not translate into reduced aneurysm growth. Nederlands Trial Register 1345.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Abdomen / ACE inhibitors / Aged / Analysis / Aneurysm / Aneurysms / Angiotensin-Converting Enzyme Inhibitors - administration & dosage / Aorta - drug effects / Aorta - pathology / Aortic Aneurysm, Abdominal - drug therapy / Aortic Aneurysm, Abdominal - metabolism / Aortic Aneurysm, Abdominal - pathology / Aortic aneurysms / Atherosclerosis / Biological response modifiers / Biology and Life Sciences / Blood pressure / Blood Vessels - drug effects / Blood Vessels - physiopathology / Cardiovascular disease / Diabetes / Drug dosages / Enzymes / Female / Gene Expression Regulation - drug effects / Growth factors / Humans / Hypertension / IL-1β / Immunohistochemistry / Inflammation / Inflammation - drug therapy / Inflammation - metabolism / Inflammation - pathology / Inhibitors / Interleukin-6 - biosynthesis / Interleukin-8 - biosynthesis / Macrophages / Macrophages - drug effects / Male / Medicine and Health Sciences / Middle Aged / Patients / Ramipril / Ramipril - administration & dosage / RNA / RNA, Messenger - biosynthesis / Studies / Vascular surgery