Tissue factor mRNA isoforms expression and modulation in lymphomonocytes and platelets of patients with acute coronary syndromes

Tissue Factor (TF), the key initiator of the coagulation cascade, is responsible for the thrombogenicity of the atherosclerotic plaque. Studies on patients with acute coronary syndrome (ACS) showed that TF plasma levels, monocyte- and platelet-associated TF are higher than in stable angina (SA) patients. Recently, an alternative spliced form of TF (asTF) has been discovered, which is soluble, circulates in the blood and exhibits procoagulant activity. Purpose. To examine TF and asTF mRNA expression in lymphomonocytes and platelets of patients with ACS, SA and in control subjects. Methods. We studied 16 patients with ACS, 14 patients with SA and 12 healthy subjects. The three groups were matched for age, gender and other clinical variables. Total RNA was extracted from peripheral lymphomonocytes and from washed platelets free of leukocyte contamination and full length TF as well as asTF mRNA levels were assessed by RT-PCR and real time PCR. Results. TF mRNA expression in resting lymphomonocytes was barely detectable in all subjects. Conversely, a consistent expression of asTF mRNA levels was observed in ACS (rel. exp: 0.38 ± 0.06, p<0.05) compared to in SA patients (rel. exp: 0.19 ± 0.04) and controls (rel. exp: 0.12 ± 0.05). In vitro lipopolysaccharide stimulation of lymphomonocytes upregulated TF mRNA expression in all samples with the highest induction observed in ACS patients (TF rel. exp. vs unstimulated sample: 151.4 ± 24.3 in ACS, 57.8 ± 5.2 in SA and 26.8 ± 3.4 in control subjects; p<0.05 vs control). By contrast, the asTF induction by lipopolysaccharide was similar in ACS and SA patients and in control subjects, (asTF rel. exp. vs unstimulated samples: 38.3 ± 13 in ACS, 54.8 ± 6.7 in SA and 56.7 ± 9.4 in control subjects). Platelet associated TF mRNA levels were significantly higher in ACS patients (rel. exp: 3.11 ± 0.51, p<0.05) compared to SA (rel. exp: 2.5 ± 0.87) and control subjects (rel. exp: 0.7 ± 0.1). No asTF mRNA was detectable in any platelet sample. Conclusions. These data provide evidence for the first time that different TF mRNA isoforms present in linfomonocytes and platelets of ACS patients can contribute to the hypercoagulability associated with the disease.