Trimetazidine offers myocardial protection in elderly coronary artery disease patients undergoing non-cardiac surgery: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Trimetazidine (TMZ) pretreatment protects cardiomyocytes during cardiac surgery. TMZ may protect elderly patients with ischaemic heart disease (IHD) undergoing non-cardiac surgery. METHODS: This was a randomized, double-blind, placebo-controlled trial (registration #ChiCTR1900025018) of patients with IHD scheduled to undergo non-cardiac surgery at Shenzhen People's Hospital (Shenzhen, Guangdong Province, China) between June 2014 and September 2015, randomized to 60 mg TMZ or placebo 12 h before surgery. The primary endpoint was the occurrence of in-hospital cardiovascular events. The secondary endpoints were myocardial ischaemia on five-lead electrocardiogram (cECG), cardiac troponin I (cTnI) elevation, cardiac death, acute coronary events, heart failure, and arrhythmia requiring treatments. RESULTS: Compared with the placebo group, the TMZ group showed a lower occurrence of in-hospital cardiovascular events (primary endpoint, 20.0% vs. 37.5%, P = 0.02), myocardial ischaemia (15.0% vs. 32.5%, P < 0.01), cTnI elevation (2.5% vs. 10%, P < 0.01), acute coronary events (10.0% vs. 20.0%, P < 0.05), heart failure (0% vs. 2.5%, P < 0.05), and arrhythmia requiring treatment (17.5% vs. 35.0%, P < 0.05). There was no acute myocardial infarction during the 30-day postoperative period. CONCLUSIONS: In elderly patients with IHD undergoing non-cardiac surgery, TMZ pretreatment was associated with myocardial protective effects. Trial registration The trial was prospectively registered at http://www.chictr.org.cn/showproj.aspx?proj=41909 with registration number [ChiCTR1900025018] (7/8/2019).

[Annexin A5 inhibits homocysteine-induced tissue factor expression and activity in vascular smooth muscle cells].

OBJECTIVE: The expression of tissue factor (TF) in vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of artherosclerosis (AS) and thrombosis. Hyperhomocysteinemia is a risk factor for AS. Annexin A5, a calcium-dependent anionic-phospholipid-binding protein has anticoagulant effect mediated by its interaction with phosphatidylserine. We investigated the effects of Annexin A5 on homocysteine (Hcy)-induced TF expression and activity in VSMCs. METHODS: Human umbilical artery VSMCs were cultured by tissue explanting method, incubated with Hcy at various concentrations in the absence and presence of Annexin A5 (50 microg/ml)/mono-TFAb (10 microg/ml). Flow Cytometry (FCM) was used to detect the expression of TF on the surface of VSMCs. Protein expression of TF was detected by Western blot. Determination of TF activity by factor Xa generation. RESULTS: The expression level of TF protein on the surface of the resting VSMCs was low [the positive rate was (4.01 +/- 2.11)%] and could be upregulated by Hcy [peaked at 1000 micromol/L, the positive rate was (37.67 +/- 4.96)%]. Annexin A5, as well as mono-TFAb could significantly inhibit Hey-induced TF membrane expression, release activity and protein expression. CONCLUSIONS: These results suggest that Annexin A5 could inhibit Hcy-induced expression and activity of TF in VSMCs as well as TF release of VSMCs. Annexin A5 might play an active role on attenuating AS and reducing coronary thrombosis by inhibiting TF pathway.