Endothelial cells microparticle-associated protein disulfide isomerase promotes platelet activation in metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a common challenge in the world, and the platelet activation is enhanced in MetS patients. However, the fundamental mechanism that underlies platelet activation in MetS remains incompletely understood. Endothelial cells are damaged seriously in MetS patients, then they release more endothelial microparticles (EMPs). After all, whether the EMPs participate in platelet activation is still obscure. If they were, how did they work? RESULTS: We demonstrated that the levels of EMPs, PMPs (platelet derived microparticles) and microparticle-carried-PDI activity increased in MetS patients. IR endothelial cells released more EMPs, the EMP-PDI was more activated. EMPs can enhance the activation of CD62P, GPIIb/IIIa and platelet aggregation and this process can be partly inhibited by PDI inhibitor such as RL90 and rutin. Activated platelets stimulated by EMPs expressed more PDI on cytoplasm and released more PMPs. MATERIALS AND METHODS: We obtained plasma from 23 MetS patients and 8 normal healthy controls. First we built insulin resistance (IR) model of human umbilical vein endothelial cells (HUVECs), and then we separated EMPs from HUVECs culture medium and used these EMPs to stimulate platelets. Levels of microparticles, P-selectin(CD62P), Glycoprotein IIb/IIIa (GPIIb/IIIa) were detected by flow cytometry and levels of EMPs were detected by enzyme-linked immunosorbent assay (ELISA). The protein disulfide isomerase (PDI) activity was detected by insulin transhydrogenase assay. Platelet aggregation was assessed by turbidimetry. CONCLUSION: EMPs can promote the activation of GPIIb/IIIa in platelets and platelet aggregation by the PDI which is carried on the surface of EMPs.

The impact of metabolic syndrome and hypertension on medical costs of patients with acute myocardial infarction at hospital.

OBJECTIVE: This study aimed to find out the impact of metabolic syndrome (MS) and hypertension on medical costs of patients with acute myocardial infarction (AMI) at hospital. METHODS: Patients with AMI at Qilu Hospital of Shandong University during January 2011 to May 2013 were separated into four groups according to whether with MS or history of hypertension. Comparison of medical costs, complication rate and cost-effectiveness ratio were analyzed. RESULTS: We found that total costs, each day costs, medical treatment costs, chemical examination costs and drug costs were significantly different in four groups. In variance analysis, MS led to high medical costs without significance. Hypertension was a significant factor influencing medical costs and lead to low medical costs. In multiple linear regression, we found that body mass index (BMI) and percutaneous coronary intervention (PCI) were important predictors of total costs and each day costs. With higher BMI and utilization rate of PCI, medical costs were increased. Trend of total costs in four groups is similar to that of the rate of PCI utilization. CONCLUSIONS: Metabolic syndrome has no impact on medical costs because of discordance in MS components. Hypertension will lead to lower PCI utilization rate, which results in less medical costs and bad hospital outcomes.

Gas6 delays senescence in vascular smooth muscle cells through the PI3K/ Akt/FoxO signaling pathway.

BACKGROUND/AIMS: Growth arrest-specific protein 6 (Gas6) is a cytokine that can be synthesized by a variety of cell types and secreted into the extracellular matrix. Previous studies have confirmed that Gas6 is involved in certain pathophysiological processes of the cardiovascular system through binding to its receptor, Axl. In the present study, we investigated the role of Gas6 in cellular senescence and explored the mechanisms underlying its activity. METHODS: We used vascular smooth muscle cells (VSMCs) to create two cellular senescence models, one for replicative senescence (RS) and one for induced senescence (IS), to test the hypothesis that Gas6 delays senescence. RESULTS: Gas6-treated cells appear relatively younger compared with non-Gas6-treated cells. In particular, Gas6-treated cells displayed decreased staining for SA-ß-Gal, fewer G1 phase cells, and decreased levels of p16(INK4a) and p21(Cip1) expression; conversely, Gas6-treated cells displayed more S phase cells and significantly increased proliferation indexes. Furthermore, in both the IS and RS models with Gas6 treatment, the levels of PI3K, p-Akt, and p-FoxO3a decreased following Axl inhibition by R428; similarly, the levels of p-Akt and p-FoxO3a also decreased following PI3K inhibition by LY294002. CONCLUSION: Gas6/Axl signaling is essential for delaying the cellular senescence process regulated by the PI3K/Akt/FoxO signaling pathway.

A medical costs study of older patients with acute myocardial infarction and metabolic syndrome in hospital.

BACKGROUND: Older patients with acute myocardial infarction (AMI) usually have a poor prognosis, but whether this poor prognosis leads to high hospital costs remains unclear. This study investigated the clinical outcomes of and costs incurred by older patients with AMI and metabolic syndrome (MS) in hospital. METHODS AND RESULTS: Patients with AMI seen at Qilu Hospital of Shandong University between January 2011 and May 2013 were separated into four groups: young non-MS patients (n=282), older non-MS patients (n=324), young MS patients (n=217), and older MS patients (n=174). We found that advanced age was significantly associated with worse clinical outcomes, and that the clinical outcomes in patients with AMI and MS are also worsened. At the same cost (RMB¥10,000), older patients with and without MS had a markedly increased number of cardiovascular incidences compared with younger patients without MS. In a comparison of the incremental cost-effectiveness ratio (ICER) of percutaneous coronary intervention, older patients without MS had a lower ICER for cardiovascular incidences and a higher ICER for cardiac event-free survival rate when compared with young patients without MS, but a lower ICER for cardiovascular incidences and a higher ICER for cardiac event-free survival rate when compared with older MS patients. CONCLUSION: Older AMI patients have poor clinical outcomes and their treatment is not cost-effective; however, the results are worse in patients with AMI and MS. Percutaneous coronary intervention is a cost-effective therapy in older patients with AMI, but its cost-effectiveness decreases in patients with AMI and MS.

Impact of type 2 diabetes mellitus on hospitalization costs in older patients with acute myocardial infarction.

BACKGROUND: The purpose of this study was to evaluate the impact of type 2 diabetes mellitus on hospitalization costs in older patients with acute myocardial infarction (MI). METHODS: Retrospective analysis of data from the case retrieval system of Qilu Hospital of Shandong University located in Jinan city of Shandong Province was done for patients with acute MI from January 1, 2011 to December 31, 2012. RESULTS: Stenting was an important factor affecting older patients' total hospitalization costs (ß=0.685, P=0.000) and treatment costs during the follow-up period (duration of hospital stay only, ß=0.508, P=0.000). Stenting was also a protective factor in the prevention of acute heart failure (HF) in older patients with acute MI during the follow-up period (odds ratio 0.189, 95% confidence interval 0.059-0.602, P=0.005). Implementation of percutaneous coronary intervention reduced the incidence of acute HF in older inpatients with acute MI (27.8% versus 4.3%, P=0.001) and without diabetes (18.2% versus 3.8%, P=0.001). Moreover, among the elderly, the incremental cost-effectiveness ratio estimate for implementing percutaneous coronary intervention in diabetic patients was higher than in nondiabetic patients. CONCLUSION: Stenting was a protective factor for preventing acute HF in the elderly during the follow-up period. From the perspective of reducing the incidence of acute HF in inpatients, implementation of percutaneous coronary intervention after an acute MI is more cost-effective in older patients with diabetes mellitus than in those without it.