title: ACE inhibitors increase type III collagen synthesis: a potential explanation for reduction in acute vascular events by ACE inhibitors.
abstract: BACKGROUND
  Large trials have shown that angiotensin converting enzyme inhibitor (ACE-I) therapy reduces the risk of myocardial infarction and stroke. Acute vascular events are thought to be initiated by plaque rupture. Animal models of atherosclerosis show an increase in extra cellular matrix when given ACE-I therapy. ACE-I therapy could influence collagen synthesis, one of the major constituents of the atherosclerotic cap.
  
  
  METHODS
  A nested case-control study was performed within the Huntingdon Aneurysm Screening Project. Subjects were assessed for arterial disease, drug history and smoking. Blood samples were taken for a measure of collagen synthesis, the amino-terminal propeptide of type III procollagen (PIIINP), lipid levels, iron metabolism and cotinine levels.
  
  
  RESULTS
  Information was available for 420 subjects. Thirty-five were taking ACE-I therapy and 385 were not. Mean serum PIIINP level was 3.5 microg/l (sd 1.3 microg/l, range: 1.7-16.5 microg/l. There was a marked increase in mean collagen turnover between subjects taking ACE-I therapy compared to those not. Mean PIIINP level for cases and controls was 4.26 microg/l (95% CI: 3.73-4.79 microg/l) versus 3.61 microg/l (95% CI: 3.48-3.75 microg/l). No differences were found for patients taking other antihypertensive drugs. After adjusting for age, weight, height, lipid levels and ferritin, PIIINP levels remained significantly higher in cases than controls: 4.14 microg/l (95% CI: 3.72-4.57 microg/l) versus 3.62 microg/l (95% CI: 3.49-3.75 microg/l) (P-value 0.02).
  
  
  CONCLUSIONS
  These results suggest that ACE-I therapy up-regulates collagen synthesis, and could improve plaque stabilisation. This may provide an explanation for the decrease in acute vascular events observed in patients on ACE-I therapy.
authors.affiliation: University of Birmingham, Birmingham Heartlands Hospital, Birmingham, UK.
authors.forename: M W
authors.initials: MW
authors.lastname: Claridge
authors.forename: S D
authors.initials: SD
authors.lastname: Hobbs
authors.forename: C R
authors.initials: CR
authors.lastname: Quick
authors.forename: N E
authors.initials: NE
authors.lastname: Day
authors.forename: A W
authors.initials: AW
authors.lastname: Bradbury
authors.forename: A B M
authors.initials: AB
authors.lastname: Wilmink
mesh_terms: D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D024061:Collagen Type III / Q000096:biosynthesis* / Q000187:drug effects*; D004739:England; D005293:Ferritins / Q000097:blood / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000188:drug therapy / Q000378:metabolism; D040242:Risk Reduction Behavior; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D002121:Calcium Channel Blockers; D008076:Cholesterol, HDL; D024061:Collagen Type III; D005293:Ferritins