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Circulation. 1996;94:2248-2253.)
© 1996 American Heart Association, Inc
K.A. Roberts, PhD; A.A.
Rezai, BS; K.E. Pinkerton, PhD; J.C. Rutledge, MD
the Departments of Internal Medicine and Veterinary Anatomy,
Physiology, and Cell Biology, University of California, Davis.
Correspondence to John C. Rutledge, MD, Division of Cardiovascular
Medicine, T.B. 172, Bioletti Way, University of California, Davis, CA 95616.
Background Previous research has shown that exposure to environmental
tobacco smoke (ETS) increases the risk of atherosclerosis.
To test the hypothesis that exposure to ETS increases LDL accumulation in the artery wall, we developed
a model to measure the rate of LDL accumulation in individually perfused rat carotid arteries after
the artery had been perfused with plasma taken from rats exposed to ETS (ETS-plasma).
Methods and Results Rats were exposed to ETS in a chamber in which
steady-state sidestream smoke was continuously circulating. After exposure, blood from the animals was collected.
Carotid arteries from unexposed rats were perfused first with normal plasma containing fluorescently
labeled LDL. Then, the same arteries (10 arteries from five rats) were perfused with ETS-plasma plus
fluorescently labeled LDL. Photometric measurements were made during perfusion of the arteries with fluorescently
labeled LDL, and rate of LDL accumulation (mV/min) and lumen volume (mV) (volume of fluorescently labeled
LDL solution) were determined. Perfusion with ETS-plasma increased the rate of LDL accumulation (mean±SEM,
6.9±1.8 mV/min) compared with control (1.6±0.40 mV/min, P
.02). LDL
accumulation was primarily dependent on LDL interaction with ETS-plasma rather than the interaction
of ETS-plasma with the artery wall. Also, ETS-plasma significantly increased lumen volume (43.3±5.1 mV) compared
with control (35.1±4.4 mV, P .005).
Conclusions Exposure to ETS acutely increased LDL accumulation in
perfused arteries. Repeated exposure to ETS may represent important early events in atherogenesis.
Key Words: smoking • lipoproteins • arteries
• atherosclerosis
AMERICAN HEART ASSOCIATION AT
http://www.circ.ahajournals.org/cgi/content/abstract/99/11/1411
Endothelial Dysfunction, Impaired Endogenous Fibrinolysis,
and Cigarette Smoking
A Mechanism for Arterial Thrombosis and Myocardial Infarction
David E. Newby, BA, BSc, BM, MRCP ; Robert A. Wright, MB, ChB, MRCP; Catherine Labinjoh, BSc, MB, ChB,
MRCP; Christopher A. Ludlam, PhD, FRCP, FRCPath; Keith A. A. Fox, BSc, MB, ChB, FRCP, FESC;
Nicholas A. Boon, MD, FRCP; David J. Webb, MD, FRCP, FRCPE, FFPM
From the Clinical Pharmacology Unit and Research Centre, University
of Edinburgh, Western General Hospital (D.E.N., C.L., D.J.W.), and the Departments of Cardiology (D.E.N., R.A.W., C.L., K.A.A.F.,
N.A.B.) and Haematology (C.A.L.), University of Edinburgh, Royal Infirmary, Edinburgh, Scotland, UK. Dr Wright is now at the
Department of Cardiology, The Ayr Hospital, Ayr, Scotland, UK.
Correspondence to Dr D.E. Newby, Clinical Pharmacology Unit
and Research Centre, University of Edinburgh, Western General Hospital, Crewe Rd, Edinburgh EH4 2XU, Scotland, UK. E-mail
d.e.newby@ed.ac.uk
Background—Effective
endogenous fibrinolysis requires rapid release of tissue plasminogen activator (tPA) from the vascular endothelium.
Smoking is a known risk factor for arterial thrombosis and myocardial infarction, and it causes endothelial
dysfunction. We therefore examined the effects of cigarette smoking on substance P–induced tPA
release in vivo in humans.
Methods and Results—Blood
flow and plasma fibrinolytic factors were measured in both forearms of 12 smokers and 12 age- and sex-matched
nonsmokers who received unilateral brachial artery infusions of substance P (2 to 8 pmol/min). In both smokers and nonsmokers, substance P caused dose-dependent
increases in blood flow and local release of plasma tPA antigen and activity (P<0.001 for
all) but had no effect on the local release of plasminogen activator inhibitor type 1. Compared with nonsmokers,
increases in forearm blood flow (P=0.03) and release of tPA antigen (P=0.04) and activity
(P<0.001) caused by substance P were reduced in smokers. The area under the curve for release of tPA
antigen and activity decreased by 51% and 53%, respectively.
Conclusions—Cigarette
smoking causes marked inhibition of substance P–induced tPA release in vivo in humans. This provides
an important mechanism whereby endothelial dysfunction may increase the risk of atherothrombosis through a reduction
in the acute fibrinolytic capacity.
Carotid arteriosclerosis
in identical twins discordant for cigarette smoking
Circulation, Vol 80, 10-16, Copyright © 1989 by American Heart Association
Plaque found to bed 3.2 times greater in smoking twins--jk
A Haapanen, M Koskenvuo, J Kaprio, YA Kesaniemi and K Heikkila
Department of Public Health, University of Turku, Finland. From a nationwide twin panel, identical twin pairs with highest discordance
in cigarette smoking were selected for a study
of arteriosclerosis (49 pairs with a mean
age of 52 years). Smoking history was obtained in
1975, 1981, and 1986. The mean life-long smoking
dose of the smoking cotwins was 20 package-years.
The smoking and nonsmoking cotwins had similar systolic and diastolic blood pressures, total
plasma cholesterol level, body mass index, and some psychosocial factors; the only difference was found in use
of alcohol, which was greater among smoking
cotwins. Duplex sonography of carotid arteries was performed. Carotid artery stenoses (narrowing of area of
the lumen with 15-60%) were found in nine pairs: in nine smoking
twins and in two of their nonsmoking cotwins
(p = 0.036). The
total area of carotid plaques was 3.2 times larger in smoking
cotwins (p less than 0.001). The thickness of the
inner layer of carotid arteries was more marked in smoking
cotwins (p less than 0.001). The size of plaques and the degree of inner layer thickening correlated with the dose
of smoking (NS). The association of smoking with carotid arteriosclerosis was highly significant even after the adjustment for age, total plasma
cholesterol level, diastolic blood pressure, and body mass index in multiple logistic regression analyses.
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