The need for an inflammatory risk profile
The need for an ‘inflammatory risk profile’ was recently discussed by several investigators. The present study is all the more significant in that it shows that a phenomenon that is influenced by various atherosclerotic risk factors and acute phase proteins is, indeed, associated with a less favorable biological profile. In addition to a significant correlation with established makers of the acute phase response (Table 1), we could show that the proportion of individuals with an increased erythrocyte adhesiveness/aggregation is significantly higher among the those with established atherosclerotic risk factors (Table 2, Table 3). Moreover, we found that the proportion of individuals with an elevated EAAT increases pari-pasu with the increment in the number of atherosclerotic risk factors (Table 4). This is in addition to a significant elevation in the degree of the erythrocyte adhesiveness/aggregation in the presence of these risk factors (Table 5), and this is especially true when multiple risk factors are present in a given individual (Table 6, Table 7, Table 8).
In order to replace other biomarkers the EAAT must be easier to use, cheaper and provide additional information. Regarding the simplicity the EAAT is as simple as performing a test of Poly (A) Tailing at the point of care by using a bedside glucometer. In fact, all that it takes is to put one drop of blood on a slide and to insert the slide in a scanner that will perform the image analysis in a fully automatic way (the results being available within a couple of minutes). Our present cost calculations are around one U.S. dollar per test. This price is significantly lower than the one needed to perform an hs-CRP assay. The EAAT is probably superior to the Wetegren sedimentation rate. In fact, we have recently presented several clinical models in which the EAAT correlated better than the ESR with the patient's disease , , , , , . If we look at the results of the present study, it seems that the EAAT correlates better than hs-CRP with the patient's biology. In fact, hs-CRP did not reach statistical significance regarding the multiplicity of risk factors in women while the EAAT was highly significant (Table 5). The same is shown in Table 7. Even for males, the P value for hs-CRP was 0.02 while that of the EAAT turned <0.0001 (Table 8). This is shown also in the discriminated analysis (Table 9).
Finally, it might be important to extend our findings beyond looking at risk factors and associating them with vascular disease per se. In fact, we have recently discussed the potential contribution that the erythrocyte adhesiveness/aggregation might have in terms of pathogenesis of the disease and especially its hemorheological disadvantage . This aspect is especially important in view of the possibility to use therapeutic interventions that might have a favorable hemorheological effect .
We conclude that it is possible to detect the presence of low grade, smoldering and subclinical inflammation by using the EAAT. This test probably reflects the presence of enhanced concentrations of inflammation-sensitive plasma proteins, part of which are directly involved in erythrocyte aggregability. These findings are significant in view of the role that these proteins might have in the pathogenesis of atherothrombosis .
Introduction The synaptic reuptake of glutamate (Glu), the major excitatory neurotransmitter in the CNS, following its release from presynaptic terminals is mediated by excitatory amino acid transporters (EAATs). The EAAT family consists of five transporters, the human EAAT1–5 subtypes corresponding to GLAST, GLT-1, EAAC1, EAAT4 and EAAT5, respectively, in rodents [1, 2, 3, 4]. EAAT2 is the major physiological subtype responsible for >90% of total Glu uptake in the brain. EAAT1 and EAAT3 also are abundantly distributed in the CNS, whereas EAAT4 and EAAT5 are expressed almost exclusively in cerebellar Purkinje cells and retina, respectively . Whereas EAAT1 and EAAT2 predominantly are expressed in glia cells, EAAT3–5 are neuronal-specific transporters [1, 2, 3, 4]. Thus, the EAAT-mediated regulation of glutamatergic signaling is delicately balanced by the regional and cellular distribution of the five transporters. In this update, we outline new insights into EAAT structure–function aspects, novel approaches to drug development in the field, and interesting findings about the physiological functions mediated by the transporters reported in recent years.