Secondhand Smoking Is Associated With Vascular Inflammation

Abstract

Background: The relative risk for cardiovascular diseases in passive smokers is similar to that of active smokers despite almost a 100-fold lower dose of inhaled cigarette smoke. However, the mechanisms underlying the surprising susceptibility of the vascular tissue to the toxins in secondhand smoke (SHS) have not been directly investigated. The aim of this study was to investigate directly vascular endothelial cell function in passive smokers.

Methods: Using a minimally invasive method of endothelial biopsy, we investigated directly the vascular endothelium in 23 healthy passive smokers, 25 healthy active smokers, and 23 healthy control subjects who had never smoked and had no regular exposure to SHS. Endothelial nitric oxide synthase (eNOS) function (expression of basal eNOS and activated eNOS [phosphorylated eNOS at serine1177 (P-eNOS)]) and expression of markers of inflammation (nuclear factor-κB [NF-κB]) and oxidative stress (nitrotyrosine) were assessed in freshly harvested venous endothelial cells by quantitative immunofluorescence.

Results: Expression of eNOS and P-eNOS was similarly reduced and expression of NF-κB was similarly increased in passive and active smokers compared with control subjects. Expression of nitrotyrosine was greater in active smokers than control subjects and similar in passive and active smokers. Brachial artery flow-mediated dilation was similarly reduced in passive and active smokers compared with control subjects, consistent with reduced endothelial NO bioavailability.

Conclusions: Secondhand smoking increases vascular endothelial inflammation and reduces active eNOS to a similar extent as active cigarette smoking, indicating direct toxic effects of SHS on the vasculature.

Figure 1 –

Expression of markers of endothelial reactivity, inflammation, and oxidative stress. Expression of eNOS, P-eNOS, nitrotyrosine, and NFκB was similar in venous endothelial cells harvested from passive (n = 23) and active smokers (n = 25). Expression of eNOS and P-eNOS was reduced whereas expression of NFκB was greater in passive smokers compared with control subjects (n = 23). Expression of nitrotyrosine was borderline significantly different between passive smokers and control subjects. eNOS = endothelial nitric oxide synthase; NFκB = nuclear factor-κB; P-eNOS = phosphorylated endothelial nitric oxide synthase.

Figure 2 –

Representative endothelial cell images from active and passive smokers and control subjects. Expression of eNOS and P-eNOS in harvested venous endothelial cells was lower in active and passive smokers than in control subjects, while expression of nitrotyrosine and NFκB was greater. Cell images were analyzed with a fluorescent microscope and captured by digital camera (× 100 magnification). See Figure 1 legend for expansion of abbreviations.

Figure 3 –

Brachial artery flow-mediated vasodilation was similar in passive (n = 23) and active smokers (n = 25) and was significantly reduced in active and passive smokers compared with control subjects (n = 23).