More recently, patients with exacerbation of idiopathic pulmonary fibrosis were reported to be associated with increased OEC proliferation. In our study, we did not find a relationship between OEC proliferation and CAD severity, although this disparate result may be related to distinct pathogenic mechanisms underlying CAD and pulmonary disease. There are a number of potential reasons for the conflicting results. Firstly, the previous studies relied solely on angiography to assess CAD severity, a technique which may have limited correlation with the physiological significance of disease severity. Although EPC number and functionality are assumed to reflect the endogenous vascular protective capacity, an alternative explanation for these conflicting BMN673 1207456-01-6 results may be that severe CAD results in ischemia and a pro-inflammatory state, thus leading to EPC mobilization. This explanation is supported by studies showing increased EPC number and clonogenic expansion capacity in vitro in patients suffering from acute coronary syndrome. These results support our findings, where we found that higher OEC levels were associated with less severe CAD. Lastly, other potential reasons for the conflicting results include significant variability between studies in the time point at which early EPC counts were performed, ranging from 4 to 12 days post culture, and the fact that EPC levels may exhibit diurnal variation, so that the differing relationships reported may simply reflect different blood collection times. Our study also explored the relationship between EPCs and the physiologic status of the coronary microcirculation, a critical determinant of cardiovascular outcomes. Previous studies on patients with cardiac syndrome X have yielded conflicting results with regards to EPC levels, with one study reporting higher EPC levels, and another reporting decreased levels and adhesive function of circulating EPCs, when compared to normal controls. Another more recent study involving patients post myocardial infarction reported that the presence of OEC was associated with reduced microvascular obstruction and infarct size, as assessed by cardiac magnetic resonance imaging, suggesting that OEC may be a marker of microvascular integrity. Additionally, EPCs have been shown to correlate with the extent of coronary collateralization by qualitative angiography. Apart from the non-uniform EPC definitions, a possible reason for the disparate results between our present study and the previous studies was that the state of the coronary microcirculation was not physiologically assessed in the previous studies. In the studies involving patients with cardiac syndrome X, the diagnosis of microcirculatory dysfunction was presumed on the basis of exclusion. Assessment of coronary microvascular dysfunction by cardiac MRI may also be compounded by the presence of concomitant epicardial coronary disease.