Salivary and plasma levels of matrix metalloproteinase-9 and myeloperoxidase at rest and after acute physical exercise in patients with coronary artery disease

Abstract

22 Background 23 Low-grade systemic inflammation is a predictor of recurrent cardiac events in patients with coronary 24 artery disease (CAD). Plasma proteins such as matrix metalloproteinase (MMP)-9 and 25 myeloperoxidase (MPO) have been shown to reflect basal as well as stress-induced inflammation in 26 CAD. Measurements of MMP-9 and MPO in saliva might pose several advantages. Therefore, we 27 investigated whether salivary levels of MMP-9 and MPO corresponded to plasma levels in patients 28 with CAD, both at rest and after acute physical exercise. 29 Methods 30 An acute bout of physical exercise on a bicycle ergometer was used as a model for stress-induced 31 inflammation. Twenty-three CAD patients performed the test on two occasions 3-6 months apart. 32 Whole unstimulated saliva was collected before, directly after and 30 min after exercise while plasma 33 was collected before and after 30 min. MMP-9 and MPO in saliva and plasma were determined by 34 Luminex. 35 Results 36 MMP-9 and MPO levels were 2-to 4-fold higher in saliva than in plasma. Within the saliva 37 compartment, and also to a great extent within the plasma compartments, MMP-9 and MPO showed 38 strong intercorrelations at all time points. However, there were no (or weak) correlations between 39 salivary and plasma MMP-9 and none between salivary and plasma MPO. 40 Conclusion 41 We conclude that salivary diagnostics cannot be used to assess systemic levels of MMP-9 and MPO in 42 CAD patients, neither at rest nor after acute physical exercise. 43 44 Key words 45 Coronary artery disease; inflammation; matrix metalloproteinase-9; myeloperoxidase; saliva 46 3 47 Introduction 48 49 Inflammation is an important component of atherosclerosis, from the formation of atherosclerotic 50 plaques to plaque destabilization eventually leading to plaque rupture and atherothrombotic events, 51 such as myocardial infarction [1]. Systemic levels of inflammatory markers can be useful to assess 52 cardiovascular risk and monitor disease activity and over the years, great efforts have been made to 53 identify relevant and easily available markers. The predictive value of markers like C-reactive protein 54 (CRP) and interleukin (IL)-6 in determining the risk of myocardial infarction is well-documented [2].55 Moreover, a number of epidemiological and clinical studies have shown that neutrophil-associated 56 proteins in plasma, such as matrix metalloproteinase (MMP)-9 and myeloperoxidase (MPO), predict 57 cardiovascular outcome [3, 4] and also relate to the extent and severity of atherosclerosis [5]. Overall, 58 there is emerging evidence that the presence of low-grade systemic inflammation should be considered 59 in clinical praxis when assessing a patient´s risk of recurrent cardiovascular events. 60 61 Low-grade inflammation is however not always detectable in plasma measures taken at rest. As has 62 been shown in various settings, stress provocation tests may add important information on the 63 individual´s susceptibility to inflammatory response [6][7][8][9]. A gr...