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(Circulation. 2004;109:1926-1929.)
© 2004 American Heart Association, Inc.

Brief Rapid Communications

Upregulation of the CD40/CD40 Ligand Dyad and Platelet-Monocyte Aggregation in Cigarette Smokers

S.A. Harding, MD; J. Sarma, MD; D.H. Josephs, BSc; N.L. Cruden, MD; J.N. Din, MD; P.J. Twomey, MD; K.A.A. Fox, MD; D.E. Newby, MD

From the Centre for Cardiovascular Sciences (S.A.H., J.S., D.H.J., N.L.C., J.N.D., K.A.A.F., D.E.N.) and Department of Clinical Biochemistry (P.J.T.), Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.

Correspondence to Dr David Newby, BHF Reader in Cardiology, The Chancellor’s Building, 49 Little France Crescent, Edinburgh, EH16 4SB, United Kingdom. E-mail d.e.newby{at}ed.ac.uk

Received October 8, 2003; de novo received December 31, 2003; revision received February 26, 2004; accepted March 2, 2004.

Background— Smoking is a potent cardiovascular risk factor and is associated with proinflammatory and prothrombotic responses. The CD40/CD40 ligand (CD40L) dyad and platelet-monocyte aggregation mediate a range of proinflammatory and prothrombotic processes thought to be important in atherothrombosis. We investigated whether expression of the CD40/CD40L dyad and platelet-monocyte aggregation are altered in cigarette smokers.

Methods and Results— C-reactive protein (CRP), soluble (s) CD40L, and surface expression of CD40L on platelets and T cells and of CD40 on monocytes and platelet-monocyte aggregates were compared in 25 cigarette smokers and 25 age- and gender-matched nonsmokers. Cigarette smokers had increased serum CRP (2.47±2.60 versus 0.94±0.96 mg/L, P=0.008) and appeared to have elevated plasma sCD40L (0.8±1.09 versus 0.37±0.21 ng/mL, P=0.07) concentrations. Smokers also had increased surface expression of CD40 on monocytes (45.9±7.7% versus 39.9±6.5%, P=0.006), of CD40L on platelets (2.9±1.0% versus 2.3±0.6%, P=0.03), and of platelet-monocyte aggregates (26.6±10.9% versus 19.7±8.6%, P=0.02). Plasma cotinine concentrations correlated with monocyte CD40 expression, platelet CD40L expression, and platelet-monocyte aggregates.

Conclusions— Cigarette smokers have upregulation of the CD40/CD40L dyad and platelet-monocyte aggregation that may account for the atherothrombotic consequences of this major cardiovascular risk factor.

Key Words: smoking • inflammation • leukocytes • platelets

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