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Coronary artery disease (CAD) is the primary critical cardiovascular event. Endothelial cell and monocyte dysfunction with subsequent extravagant inflammation are the main causes of vessel damage in CAD. Thus, strategies that repress cell death and manage unsuitable pro-inflammatory responses in CAD are potential therapeutic strategies for improving the clinical prognosis of patients with CAD. SIRT1 (Sirtuin 1) plays an important role in regulating cellular physiological processes. SIRT1 is also thought to protect the cardiovascular system by means of its antioxidant, anti-inflammation and anti-apoptosis activities. In the present study, we found that the SIRT1 expression levels were repressed and the acetylated p53 expression levels were enhanced in the monocytes of patients with CAD. LOX-1/oxidative stress was also up-regulated in the monocytes of patients with CAD, thereby increasing pro-apoptotic events and pro-inflammatory responses. We also demonstrated that monocytes from CAD patients caused endothelial adhesion molecule activation and the adherence of monocytes and endothelial cells. Our findings may explain why CAD patients remain at an increased risk of long-term recurrent ischemic events and provide new knowledge regarding the management of clinical CAD patients.

Coronary artery disease (CAD) is a critical cardiovascular disease and a cause of high morbidity and mortality in this world. Hyperhomocysteinemia (HHcy) has been suggested as a risk factor for CAD. In addition, SIRT1 (sirtuin 1) has been reported to play a protective role in a variety of diseases, especially in the cardiovascular system. The main purpose of this study was to investigate the effects of exercise training on apoptosis and inflammation in HHcy animals. We also tested whether exercise protected against Hhcy-induced dysfunction of endothelium through modulation of SIRT1. C57BL mice (8 in each group) were fed with or without 1% L-methionine (w/w) in water for 4 months to induce HHcy. We found that Hhcy repressed SIRT1 and AMPK expression and increased NADPH oxidase activity. Plasma MDA, endothelium LOX-1 and p-p38 were up-regulated by Hhcy induction. NF-κB and it downstream molecules were activated under Hhcy situation, thereby promoting pro-inflammatory responses. Moreover, we also reported that Hhcy caused endothelium apoptosis involving Akt inhibition and mitochondria-dependent apoptotic pathways. Exercise training significantly protected against endothelium from Hhcy caused oxidative injuries. In addition, EX527 (SIRT1 inhibitor) reduced the therapeutic effects by exercise. Our results had indicated that exercise training prevent the development of atherosclerosis through SIRT1 activation and oxidative stress inhibition under Hhcy situation.

BackgroundPulmonary hypertension (PH) is a rare but fatal condition. Large‐scale studies to examine the prognostic factors are lacking. In the present study, we aimed to investigate the factors associated with overall mortality in PH patients.Methods and ResultsBased on Taiwan's National Health Insurance Database, we identified 1092 newly identified PH patients between 1999 and 2011. These patients were matched with 8736 healthy subjects based on propensity score calculated with age, sex, and chronic cardiovascular risk factors. Overall mortality, death incidence rate ratio, and hazard ratio were calculated. Patients with PH had a higher mortality than controls (56.45 versus 18.51 per 1000 person‐years, P<0.0001), with hazard ratio at 3.3 (95% CI: 2.92–3.73, P<0.001). The long‐term survival rates of the PH patients at 1, 5, and 10 years were 87.9%, 72.5%, and 62.6%, respectively, which were significantly lower than controls with 98.4%, 90.8%, and 83.6% at 1, 5, and 10 years, respectively. Among patients with PH, the mortality rate was higher in the older and male patients. However, after stratifying by age and sex, the younger (<50 years) and female patients had a higher risk. Regarding different etiologies of PH, chronic obstructive pulmonary disease and pulmonary embolism led to most cases of mortality (adjusted hazard ratio: 3.2, 95% CI: 2.76–3.71 and 4.64, 95% CI: 2.74–7.87, P<0.05).Conclusions PH has high mortality, especially in females, and patients with younger age and with chronic diseases. Chronic obstructive pulmonary disease and pulmonary embolism contributed to an increased risk of mortality in PH patients.

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