The Increased TIGIT-Expressing CD3+CD56+ Cells Are Associated with Coronary Artery Disease and Its Inflammatory Environment.

We aimed to examine the correlation of T-cell immunoglobulin and ITIM domain (TIGIT)-expressing CD3 + CD56 + cells (TNKS) with coronary artery disease (CAD), atherosclerotic lesion progression, and inflammatory environment. A total of 199 subjects, including 98 patients with acute coronary syndrome (ACS), 52 patients with chronic coronary syndrome (CCS), and 49 control subjects, were recruited in the study. The TIGIT-expressing TNKS were quantified by flow cytometric analysis; the severity of coronary artery lesions was evaluated by the Gensini score. Whole blood cells were stimulated with interleukin-2 (IL-2), interleukin-7 (IL-7), and interleukin-15 (IL-15) in presence or absence of STAT, PI3K, and P38 MAPK inhibitors, respectively. The TIGIT-expressing TNKS was significantly increased in patients with CAD, ACS, and CCS compared to the control group (P < 0.05). The TIGIT-expressing TNKS were independent predictors of CAD, ACS and CCS (P < 0.05). The TIGIT-expressing TNKS were positively associated with Gensini score (P < 0.05). The TIGIT-expressing TNKS was positively correlated with age, and being male (P < 0.05). The inflammatory microenviroment with increased IL-2, IL-7, and IL-15 contributed to upregulation of TIGIT expression in TNKS. PI3K and P38 MAPK inhibitors could inhibit the upregulation of TIGIT expression in TNKS induced by IL-2, IL-7, and IL-15. The TIGIT-expressing TNKS may be involved in common pathogenesis of ACS and CCS, and atherosclerotic lesion progression. Meanwhile, the increased TIGIT-expressing TNKS might be associated with a proatherogenic microenvironment or inflammatory microenvironment. PI3K and P38 MAPK signaling pathways were involved in the regulation of TIGIT expression.

Sex-Related Differences in Sitagliptin Treatment in Type 2 Diabetes: Results from the PROLOGUE Trial.

BACKGROUND At present, whether sitagliptin has sex-related differences in effect on atherosclerosis in type 2 diabetes mellitus (T2DM) patients is unknown. The purpose of this study was to investigate whether there is sex-related difference in the effect of sitagliptin on atherosclerosis in T2DM patients. MATERIAL AND METHODS In the PROLOGUE trial, 222 patients were allocated to the sitagliptin group and 220 patients were allocated to the conventional group. Carotid artery intima-media thickness (IMT) was assessed at baseline, 12 months, and 24 months. RESULTS In male patients, sitagliptin significantly reduced the mean IMT (0.84±0.41 mm vs 1.02±0.67 mm, P=0.013) and the maximum IMT (1.14±0.59 mm vs 1.39±0.88 mm, P=0.016) in the right internal carotid arteries (ICA) compared to the conventional group at 12 months. Similarly, sitagliptin significantly reduced the maximum IMT (1.09±0.52 mm vs 1.28±0.77 mm, P=0.049) in the right ICA compared to the conventional group at 24 months, but no difference was found in the mean IMT in the right ICA between groups at 24 months. In female patients, sitagliptin significantly reduced the mean IMT (1.01±0.47 mm vs 1.23±0.51 mm, P=0.049) and the maximum IMT (1.39±0.65 mm vs 1.71±0.77 mm, P=0.042) in the right bulb compared to the conventional group at 12 months. However, the group differences were not observed in mean IMT and maximum IMT at 24 months. CONCLUSIONS Our results suggest that sitagliptin slows the progression of right carotid IMT in male patients. However, more research is needed to validate this finding in female patients.