Defining symptomatic and asymptomatic by transcriptional profile

Morphological features, although clearly indicators of a potentially vulnerable plaque may not auger the onset of clinical symptoms.

Objectives. We studied whether the thrombomodulatory transcriptional profile of carotid lesions are a more accurate measure of plaque vulnerability.

Methods. Patients were stratified into three groups: Group I (n=9), had a recorded event within one month of surgery, Group II (n=10), had a recorded event greater than one month before surgery, and Group III (n=11), had been symptom free for at least six months prior to surgery.mRNA was extracted from carotid plaques.Expression of thrombomodulatory factors; tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and thrombomodulin (TM), was measured using quantitative RT-PCR.

Results. Expression was analysed between the three groups using Kruskal-Wallis test.Values given below represent the median and interquartile range (x 1000)

                                                        Group I                         Group II                          Group III

                                                        (n=9)                            (n=10)                             (n=11)

TF(p = 0.036)                                17 (4 — 60)                 7 (0.2 — 1.7)                 1.2 (0.1 — 5)

PAI-1 (p = 0.046)                          134 (66 — 280)          6 (2.1 — 57)                  6 (1.4 — 101)

tPA(p = 0.026)                               60 (23.3 — 106)        3 (0.6 — 7.1)                 3 (1.8 — 14.9)

TM(p = 0.033)                                24 (11.4 — 10.7)       2 (0.3 10.7)                    3 (0.9 — 7.9)

Conclusions. (1) Elevated expression of TM, PAI-1, TF and tPA define the more unstable plaques.

(2) Within one month following a clinical event, homeostatic processes have restored the thrombomodulatory status of the culprit lesion(s) such that they are indistinguishable from that of quiescent plaques from asymptomatic patients.