Fibroblast growth factor 21 (FGF21), a hormone with multiple metabolic properties, has proven to be pleiotropic biological effects and may play pivotal role in numerous cardiovascular and metabolic diseases in the future. Vascular calcification (VC) is a concomitant pathological process of various cardiovascular and metabolic diseases. However, the effects of FGF21 on VC remain unclear. Therefore, in this research, we aimed to explore the roles and mechanisms of FGF21 in VC induced by vitamin D3 plus nicotine (VDN) treatment rats. After 28 days VDN treatment, the calcium overload was confirmed by blood pressure, ultrasound imaging, calcium content, ALP activity and aortic pathological characteristics. In terms of FGF21, exogenous FGF21 can ameliorate the elevation of blood pressure, aortic calcification and related injury in VC rats. To investigate the mechanisms of FGF21 on VC, the endoplasmic reticulum stress (ERS) mediated apoptosis pathways were tested. As a method to detect apoptosis, the increased positive TUNEL staining cells were alleviated by FGF21 treatment. Furthermore, exogenous FGF21 can suppress the increased ERS chaperone, GRP78, in the calcified aortas. In the three pathways of ERS mediated apoptosis, we found CHOP pathway and caspase-12 pathway were involved in the treatment of FGF21, but not p-JNK/JNK pathway. Our study proved for the first time that FGF21 can inhibit the progress of VC by alleviating ERS mediated apoptosis in rats. FGF21 might be a new target for preventing and treating VC.

Percutaneous coronary intervention (PCI), especially coronary stent implantation, has been shown to be an effective treatment for coronary artery disease. However, in-stent restenosis is one of the longstanding unsolvable problems following PCI. Although stents implanted inside narrowed vessels recover normal flux of blood flows, they instantaneously change the wall shear stress (WSS) distribution on the vessel surface. Improper stent implantation positions bring high possibilities of restenosis as it enlarges the low WSS regions and subsequently stimulates more epithelial cell outgrowth on vessel walls. To optimize the stent position for lowering the risk of restenosis, we successfully established a digital three-dimensional (3-D) model based on a real clinical coronary artery and analysed the optimal stenting strategies by computational simulation. Via microfabrication and 3-D printing technology, the digital model was also converted into in vitro microfluidic models with 3-D micro channels. Simultaneously, physicians placed real stents inside them; i.e., they performed “virtual surgeries”. The hydrodynamic experimental results showed that the microfluidic models highly inosculated the simulations. Therefore, our study not only demonstrated that the half-cross stenting strategy could maximally reduce restenosis risks but also indicated that 3-D printing combined with clinical image reconstruction is a promising method for future angiocardiopathy research.

It is suggested that cholesterol efflux mediated by ATP binding cassette transporter A1 (ABCA1) plays an important role in anti-atherogenesis. However, the effects of inflammatory cytokines on ABCA1 expression and cholesterol accumulation in foam cells are little known. This study investigates the effects of tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) on ABCA1 expression and cholesterol content in THP-1 macrophage-derived foam cells. ABCA1mRNA and protein levels were determined by RT-PCR and Western blot, respectively. The total cholesterol content in THP-1 macrophage-derived foam cells was detected by the zymochemistry method. Results revealed that TNF-alpha could increase cholesterol content by down-regulating ABCA1 expression in a time-dependent manner in THP-1 macrophage-derived foam cells, which may contribute to its pro-atherosclerotic effect. In addition IL-10 time-dependently decreased cholesterol accumulation by up-regulating ABCA1 expression and inhibited the down-regulation of ABCA1 by TNF-alpha in THP-1 macrophage-derived foam cells, which may be one of the mechanisms of IL-10 contributing to its anti-atherosclerotic action.