In coronary arteries, plaque disruption, the major acute clinical manifestations of atherosclerosis, leads to a subsequent cardiac event, such as acute myocardial infarction (AMI) and unstable angina pectoris (UA). Numerous reports have shown that high expression of MMP-9 (matrix metalloproteinase-9), MMP-13 (matrix metalloproteinase-13) and EMMPRIN (extracellular matrix metalloproteinase induce) in monocyte/macrophage results in the plaque progression and destabilization. Curcumin exerts well-known anti-inflammatory and antioxidant effects and probably has a protective role in the atherosclerosis. The purpose of our study was to investigate the molecular mechanisms by which curcumin affects MMP-9, MMP13 and EMMPRIN in PMA (phorbol 12-myristate 13-acetate) induced macrophages. Human monocytic cells (THP-1 cells) were pretreated with curcumin or compound C for 1 h, and then induced by PMA for 48 h. Total RNA and proteins were collected for real-time PCR and Western blot analysis, respectively. In the present study, the exposure to curcumin resulted in attenuated JNK, p38, and ERK activation and decreased expression of MMP-9, MMP-13 and EMMPRIN in PMA induced macrophages. Moreover, we demonstrated that AMPK (AMP-activated protein kinase) and PKC (Protein Kinase C) was activated by PMA during monocyte/macrophage differentiation. Furthermore, curcumin reversed PMA stimulated PKC activation and suppressed the chronic activation of AMPK, which in turn reduced the expression of MMP-9, MMP-13 and EMMPRIN. Therefore, it is suggested that curcumin by inhibiting AMPK-MAPK (mitogen activated protein kinase) and PKC pathway may led to down-regulated EMMPRIN, MMP-9 and MMP-13 expression in PMA-induced THP-1 cells.

Background: Rapid reperfusion of ST-segment elevation myocardial infarction (STEMI) has been challenging during the coronavirus disease 2019 (COVID-19) outbreak. Whether and to what degree there will be a residual impact when the COVID-19 pandemic has passed is unclear. Methods: This nationwide retrospective study was based on electronic records of STEMI patients registered in the Chinese Cardiovascular Association Database. Results: We analyzed 141,375 STEMI patients (including 4871 patients in Hubei province, where 80% of COVID-19 cases in China occurred in 2019–2020) during the pre-outbreak (23 October 2019–22 January 2020), outbreak (23 January 2020–22 April 2020), and post-outbreak (23 April 2020–22 July 2020) periods. In the post-outbreak period in Hubei province, the increased in-hospital mortality dropped to become insignificant (adjusted odds ratio compared to the pre-outbreak level (aOR) 1.40, [95% confidential interval (CI): 0.97–2.03]) and was lower than that in the outbreak period (1.62 [1.09–2.41]). The decreased odds of primary percutaneous coronary intervention (PCI) (0.73 [0.55–0.96]) and timely reperfusion (0.74 [0.62–0.88]) persisted, although they were substantially improved compared to the outbreak period (aOR of primary PCI: 0.23 [0.18–0.30] and timely reperfusion: 0.43 [0.35–0.53]). The residual impact of COVID-19 on STEMI in the post-outbreak period in non-Hubei provinces was insignificant. Conclusions: Residual pandemic impacts on STEMI management persisted after the first wave of the COVID-19 outbreak in Hubei province, the earliest and hardest hit area in China.