Identification of differentially expressed proteins in blood plasma of control and cigarette smoke-exposed mice by 2-D DIGE/MS.

Cigarette smoke exposure is known to induce obstructive lung disease and several cardiovascular disease states in humans and also in animal models. Smoking leads to oxidative stress and inflammation that are important in triggering pulmonary and cardiovascular disease. The objective of the current study was to quantify differences in expression levels of plasma proteins of cigarette smoke -exposed and control mice, at the time of disease onset, and identify these proteins for use as potential biomarkers of the onset of smoking-induced disease. We utilized 2-D DIGE/MS to characterize these proteomic changes. 2-D DIGE of plasma samples identified 11 differentially expressed proteins in cigarette smoke -exposed mice. From these 11 proteins, 9 were downregulated and 2 were upregulated. The proteins identified are involved in vascular function, coagulation, metabolism and immune function. Among these, the alterations in fibrinogen (2.2-fold decrease), α-1-antitrypsin (1.8-fold increase) and arginase (4.5-fold decrease) are of particular interest since these have been directly linked to cardiovascular and lung pathology. Differences in expression levels of these proteins were also confirmed by immunoblotting. Thus, we observe that chronic cigarette smoke exposure in mice leads to prominent changes in the protein expression profile of blood plasma and these changes in turn can potentially serve as markers predictive of the onset and progression of cardiovascular and pulmonary disease.