Advance in the pharmacological and comorbidities management of heart failure with preserved ejection fraction: evidence from clinical trials.

The prevalence of heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of the total heart failure population, and with the aging of the population and the increasing prevalence of hypertension, obesity, and type 2 diabetes (T2DM), the incidence of HFpEF continues to rise and has become the most common subtype of heart failure. Compared with heart failure with reduced ejection fraction, HFpEF has a more complex pathophysiology and is more often associated with hypertension, T2DM, obesity, atrial fibrillation, renal insufficiency, pulmonary hypertension, obstructive sleep apnea, and other comorbidities. HFpEF has generally been considered a syndrome with high phenotypic heterogeneity, and no effective treatments have been shown to reduce mortality to date. Diuretics and comorbidity management are traditional treatments for HFpEF; however, they are mostly empirical due to a lack of clinical evidence in the setting of HFpEF. With the EMPEROR-Preserved and DELIVER results, sodium-glucose cotransporter 2 inhibitors become the first evidence-based therapies to reduce rehospitalization for heart failure. Subgroup analyses of the PARAGON-HF, TOPCAT, and CHARM-Preserved trials suggest that angiotensin receptor-neprilysin inhibitors, spironolactone, and angiotensin II receptor blockers may be beneficial in patients at the lower end of the ejection fraction spectrum. Other potential pharmacotherapies represented by non-steroidal mineralocorticoid receptor antagonists finerenone and antifibrotic agent pirfenidone also hold promise for the treatment of HFpEF. This article intends to review the clinical evidence on current pharmacotherapies of HFpEF, as well as the comorbidities management of atrial fibrillation, hypertension, T2DM, obesity, pulmonary hypertension, renal insufficiency, obstructive sleep apnea, and iron deficiency, to optimize the clinical management of HFpEF.

Liraglutide ameliorates oxidized LDL-induced endothelial dysfunction by GLP-1R-dependent downregulation of LOX-1-mediated oxidative stress and inflammation.

OBJECTIVE: To investigate the effects of glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide on endothelial dysfunction in LDL receptor-deficient (LDLR-KO) mice and ox-LDL-challenged human umbilical vein endothelial cells (HUVECs) and its possible mechanism. METHODS: LDLR-KO mice were randomly treated with normal saline, liraglutide, or liraglutide plus a GLP-1R antagonist exendin-9 for four weeks. In parallel, HUVECs were cultured with ox-LDL alone or combined with liraglutide, in the presence or absence of lectin-like ox-LDL receptor-1(LOX-1) overexpression or GLP-1R knockdown. Endothelial-dependent relaxation and LOX-1 protein expression of thoracic aorta, circulating levels of oxidative and inflammatory markers in mice, and cell survival, reactive oxygen species production, and expression of adhesion molecules and signal regulators in ox-LDL cultured endothelial cells were measured. RESULTS: liraglutide effectively enhanced acetylcholine-induced vasodilation, reduced LOX-1 expression in aortas, and decreased circulatory oxidative and inflammatory levels in LDLR-KO mice, which were abolished by cotreatment with exendin-9. HUVECs exposed to ox-LDL exhibited reduced cell viability, increased reactive oxygen species production and apoptosis, and elevated protein expression of ICAM-1, VCAM-1, LOX-1, NOX4, and NF-κB, which were markedly ameliorated by liraglutide treatment. The protective effects of liraglutide against ox-LDL-induced cell injury were abrogated in HUVECs overexpressing LOX-1 or silencing GLP-1R. CONCLUSIONS: Liraglutide improved oxidized LDL-induced endothelial dysfunction via GLP-1R-dependent downregulation of LOX-1-mediated oxidative stress and inflammation.

Dynamic changes of myocardial collagen metabolism in pressure-overloaded rats / 中国病理生理杂志

AIM: To observe the dynamic changes of myocardial collagen metabolism in pressure-overloaded rats.METHODS: The pressure-overloaded rat model was established by partial abdominal aortic coarctation.The rats underwent surgery but not constrictive were used as sham-operated control group.The rats were euthanized at 3, 4, 8 and 12 weeks.The body mass, heart mass and left ventricular mass were weighed, and the heart mass index (HMI) and left ventricle mass index (LVMI) were calculated.Masson trichrome staining was used on the myocardial sections, alkaline hydrolysis was used to detect the content of myocardial hydroxyproline (HYP), and the serum levels of procollagen type I carboxy-terminal peptide (PICP), procollagen type III amino-terminal peptide (PIIINT), and collagen C telopeptide type I (CTX-I) were also measured.RESULTS: Compared with sham-operated control group, the collagen deposition was evident, and collagen volume fraction (CVF) was increased significantly in model group (P<0.01), which further increased over time.HMI, LVMI and HYP significantly increased in model group (P<0.05), and HYP showed a tendency to increase over time.In addition, the serum concentration of PICP was increased significantly in model group, and the difference was significant at 4, 8 and 12 weeks (P<0.05).The serum concentration of PIIINP was increased significantly, but CTX-I was lowered significantly in model group (P<0.01).CONCLUSION: In the state of pressure overload, myocardial collagen metabolism is in disorder, and myocardial fibrosis is the major pathological change, which further increases over time.

Pharmacodynamic Study of Chongcaodihuang Syrupus / 中国药房

OBJECTIVE:To study the effects of Chongcaodihuang(CCDH)syrupus on immune function and antistress ability.METHODS:The experiments were carried out to investigate the effects of CCDH on weight of immune organs,the phagocytization of the monocytes by using the method of carbon particles expurgation,the content of antibody of hemolysin in serum,and time of swimming and hypoxia tolerance in mice.RESULTS:CCDH could enhance weight of immune organs,the phagocytization of the monocytes and increase the content of antibody of hemolysin in serum.It can also delay the time of swimming and strengthen hypoxia tolerance in mice.CONCLUSION:CCDH significantly improve immune function and antistress ability of mice.