The role of inflammation in heart failure with preserved ejection fraction / 生理学报

Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure characterized by left ventricular diastolic dysfunction with preserved ejection fraction. With the aging of the population and the increasing prevalence of metabolic diseases, such as hypertension, obesity and diabetes, the prevalence of HFpEF is increasing. Compared with heart failure with reduced ejection fraction (HFrEF), conventional anti-heart failure drugs failed to reduce the mortality in HFpEF due to the complex pathophysiological mechanism and multiple comorbidities of HFpEF. It is known that the main changes of cardiac structure of in HFpEF are cardiac hypertrophy, myocardial fibrosis and left ventricular hypertrophy, and HFpEF is commonly associated with obesity, diabetes, hypertension, renal dysfunction and other diseases, but how these comorbidities cause structural and functional damage to the heart is not completely clear. Recent studies have shown that immune inflammatory response plays a vital role in the progression of HFpEF. This review focuses on the latest research progress in the role of inflammation in the process of HFpEF and the potential application of anti-inflammatory therapy in HFpEF, hoping to provide new research ideas and theoretical basis for the clinical prevention and treatment in HFpEF.

Hypoxia amplifies lipopolysaccharide-induced IL-1β expression in macrophages / 基础医学与临床

Objective To investigate the effect of hypoxia on the expression of IL-1βin macrophages.Methods RAW264.7 cells were treated with normoxia(21%O2),hypoxia(2%O2), normoxia(21%O2)plus LPS and hypoxia(2%O2)plus LPS.RT-qPCR was used to detect the mRNA expression of Vegf,Nlrp3 and Il1b.Western blot was used to detect the protein expression of HIF-1α,NLRP3,caspase-1,cleaved caspase-1,Pro-IL-1βand IL-1β.The peritoneal macrophages of Vhlfl/fl/Apoe-/-mice and VhlΔMac/Apoe-/-mice were treated with or without LPS.RT-qPCR was used to detect the mRNA expression of Vhl,Nlrp3,Il1b and Il6.Results Compared with nor-moxia, hypoxia significantly increased mRNA of Vegf, Nlrp3 and Il1b in RAW264.7(P<0.01).Hypoxia increased mRNA and protein of NLRP 3 and IL-1βin RAW264.7 induced with LPS comparing with normoxia(P<0.01).Hypoxia had no effects on the activation of caspase-1 and the subsequent maturation of Pro-IL-1βinduced with LPS in RAW264.7.Compared with Vhlfl/fl/Apoe-/-peritoneal macrophages,VhlΔMac/Apoe-/-peritoneal macro-phages showed significantly increased mRNA levels of Nlrp3,Il1b and Il6 induced with LPS(P<0.05).Conclu-sions Hypoxia amplifies lipopolysaccharide-induced IL-1βexpression in macrophages.

Synergistic proliferation induced by insulin and glycated serum albumin in rat vascular smooth muscle cells / 生理学报

Hyperglycemia, advanced glycation end products (AGEs), hyperinsulinemia and dyslipidemia may play roles in the development of diabetes-associated atherosclerosis and post-angioplasty restenosis. Clinically, their effects seem to be synergic. However, few studies have focused on the synergistic action of these factors. In the present study, we investigated whether glycated serum albumin (GSA) has a synergistic effect with insulin on the proliferation of vascular smooth muscle cells (VSMCs). VSMCs were isolated from rat thoracic aortas and cultured in fetal bovine serum (FBS)-free medium for 24 h, then exposed to GSA, insulin or GSA + insulin for 48 h with or without pretreatment of mitogen-activated protein kinase (MAPK) inhibitors or the antioxidant N-acetylcysteine (NAC). Cell growth rate was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay or cell counting. The changes of phosphorylated-p38 MAPK and phosphorylated-C-Jun N-terminal kinase 1/2 (JNK1/2) were measured by Western blot analysis. The results showed that only p38 MAPK, but not JNK was activated by GSA and insulin co-incubation. VSMC proliferation was increased by insulin (10-1000 nmol/L) or GSA (10, 100 microg/mL). Co-incubation of insulin (100 nmol/L) and GSA (100 mug/mL) caused a more potent increase in VSMC proliferation than insulin or GSA incubation alone. p38 MAPK inhibitor, SB203580, as well as NAC, could inhibit the VSMC proliferation induced by co-incubation of GSA and insulin. The results show that insulin enhances GSA-induced VSMC proliferation, which may be mediated through a reactive oxygen species (ROS)-p38 MAPK pathway. The synergism of AGEs and insulin may play a detrimental role in the pathogenesis of diabetic atherosclerosis and post-angioplasty restenosis.