The rising prevalence of cardiovascular disease has become a global health concern. The occurrence of cardiovascular disease is the result of long-term interaction of many risk factors, one of which is diabetes. As a novel anti-diabetic drug, DPP4 inhibitor has been proven to be cardiovascular safe in five recently completed cardiovascular outcome trials. Accumulating studies suggest that DPP4 inhibitor has potential benefits in a variety of cardiovascular diseases, including hypertension, calcified aortic valve disease, coronary atherosclerosis, and heart failure. On the one hand, in addition to improving blood glucose control, DPP4 inhibitor is involved in controlling cardiovascular risk factors. On the other hand, DPP4 inhibitor directly regulates the occurrence and progression of cardiovascular diseases through a variety of mechanisms. In this review, we summarize the recent advances of DPP4 in cardiovascular disease, aiming to discuss DPP4 inhibitor as a potential option for cardiovascular therapy.
Fournier's gangrene (FG) is a life-threatening and special form of necrotizing fasciitis, characterized by occult onset, rapid progress and high mortality, occurring mainly in men over 50 years of age. Risk factors of FG include diabetes, HIV infection, chronic alcoholism and other immunosuppressive state. FG was previously considered as an idiopathic disease, but in fact, three quarters of the infections originated from the skin, urethra and gastrointestinal tract. Initial symptoms of FG are often inconsistent with severity and can progress promptly to fatal infection. Although the treatment measures of FG have been improved in recent years, the mortality does not seem to have decreased significantly and remains at 20% -30%. The time to identify FG and the waiting period before surgical debridement are directly related to the prognosis. Therefore, in addition to the combination of intensive fluid resuscitation and broad-spectrum antibiotics, treatment of FG should particularly emphasize the importance of early surgical debridement assisted with fecal diversion and skin reconstruction when necessary. This paper is to briefly summarize the progress in the definition, epidemiology, clinical manifestations, diagnosis, treatment and prognosis of Fournier's gangrene in recent years, more importantly, illustrates the importance of multidisciplinary cooperation in the management of FG.
The local heterogeneity in the distribution of atherosclerotic lesions is caused by local flow patterns. The integrin family plays crucial regulatory roles in diverse biological processes, but knowledge of integrin β4 (ITGB4) in shear stress-induced atherosclerosis is limited. This study clarified that low shear stress (LSS) regulates the generation of ITGB4 in endothelial cells with atheroprone phenotype to identify ITGB4’s role in atherosclerosis. We found that LSS led to an increase in ITGB4 protein expression both in vitro and in vivo. ITGB4 knockdown attenuated inflammation and ROS generation in human umbilical vein endothelial cells (HUVECs) and reduced atherosclerotic lesion areas in ApoE-/- mice fed with HFD, largely independent of effects on the lipid profile. Mechanistically, ITGB4 knockdown altered the phosphorylation levels of SRC, FAK, and NFκB in HUVECs under LSS conditions. In addition, the knockdown of NFκB inhibited the production of ITGB4 and SRC phosphorylation, and the knockdown of SRC downregulated ITGB4 protein expression and NFκB activation. These data demonstrate a critical role of ITGB4 in atherosclerosis via modulation of endothelial cell inflammation, and ITGB4/SRC/NFκB might form a positive feedback loop in the regulation of endothelial cell inflammation.
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