Impaired coronary tissue plasminogen activator release is associated with coronary atherosclerosis and cigarette smoking: direct link between endothelial dysfunction and atherothrombosis

D E Newby, A L McLeod, N G Uren, L Flint, C A Ludlam, D J Webb, K A Fox, N A Boon

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: The aim of the study was to establish the influence of proximal coronary artery atheroma and smoking habit on the stimulated release of tissue plasminogen activator (tPA) from the heart.

METHODS AND RESULTS: After diagnostic coronary angiography in 25 patients, the left anterior descending coronary artery (LAD) was instrumented, and the proximal LAD plaque volume was determined by use of intravascular ultrasound (IVUS). Blood flow and fibrinolytic responses to selective LAD infusion of saline, substance P (10 to 40 pmol/min; endothelium-dependent), and sodium nitroprusside (5 to 20 microgram/min; endothelium-independent) were measured by intracoronary IVUS and Doppler, combined with arterial and coronary sinus blood sampling. Mean plaque burden was 5.5+/-0.8 mm(3)/mm vessel (range 0.6 to 13.7 mm(3)/mm vessel). LAD blood flow increased with both substance P and sodium nitroprusside (P<0.001), although coronary sinus plasma tPA antigen and activity concentrations increased only during substance P infusion (P<0.006 for both). There was a strong inverse correlation between the LAD plaque burden and release of active tPA (r=-0.61, P=0.003). Cigarette smoking was associated with impaired coronary release of active tPA (current smokers, 31+/-23 IU/min; ex-smokers, 50+/-33 IU/min; nonsmokers 202+/-73 IU/min; P<0.05).

CONCLUSIONS: We found that both the coronary atheromatous plaque burden and smoking habit are associated with a reduced acute local fibrinolytic capacity of the heart. These important findings provide evidence of a direct link between endogenous fibrinolysis, endothelial dysfunction, and atherothrombosis in the coronary circulation and may explain the greater efficacy of thrombolytic therapy for myocardial infarction in cigarette smokers.

Original languageEnglish
Pages (from-to)1936-41
Number of pages6
JournalCirculation
Volume103
Issue number15
DOIs
Publication statusPublished - 17 Apr 2001

Keywords

  • Area Under Curve
  • Blood Flow Velocity
  • Cardiac Catheterization
  • Coronary Artery Disease
  • Coronary Circulation
  • Coronary Thrombosis
  • Coronary Vessels
  • Endosonography
  • Endothelium, Vascular
  • Female
  • Humans
  • Infusions, Intra-Arterial
  • Male
  • Middle Aged
  • Nitroprusside
  • Plasminogen Activator Inhibitor 1
  • Regression Analysis
  • Risk Factors
  • Smoking
  • Substance P
  • Tissue Plasminogen Activator
  • Vasodilator Agents

Fingerprint

Dive into the research topics of 'Impaired coronary tissue plasminogen activator release is associated with coronary atherosclerosis and cigarette smoking: direct link between endothelial dysfunction and atherothrombosis'. Together they form a unique fingerprint.

Cite this