Sacubitril/valsartan attenuates myocardial inflammation, hypertrophy, and fibrosis in rats with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) represents a multifaceted syndrome related to complex pathologic mechanisms. Sacubitril/valsartan (Sac/val) has demonstrated therapeutic efficacy in HFpEF treatment. However, additional research is required to elucidate its pharmacological mechanisms. Accordingly, this study aimed to explore the potential therapeutic effects of Sac/val in HFpEF rats and the underlying molecular mechanisms. In this study, rats with HFpEF were induced by subjecting spontaneously hypertensive rats to a diet rich in fats, salts, and sugars, along with administering streptozotocin. Subsequently, they were administered Sac/val at a daily dosage of 18 mg/kg. Finally, cardiac structure and function were assessed using echocardiography; Hematoxylin and eosin staining and Masson's trichrome staining were employed to evaluate the pathological changes; Quantitative real-time polymerase chain reaction and Western blot analysis were conducted to determine the expression of pertinent mRNA and proteins. Sac/val treatment attenuated left ventricular (LV) remodeling and diastolic dysfunction in HFpEF rats, possibly related to its anti-inflammatory, anti-hypertrophic, and anti-fibrotic efficacy. Mechanistically, Sac/val might inhibit inflammation by down-regulating cell adhesion molecule (intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial cell adhesion molecule-1 (VCAM-1)) expression. Additionally, it blocked the phosphorylation of glycogen synthase kinase 3ß (GSK-3ß) to prevent cardiomyocyte hypertrophy. Furthermore, it effectively suppressed myocardial fibrosis by inhibiting the transforming growth factor-beta1 (TGF-ß1)/Smads pathway. Our findings suggest that Sac/val improved LV remodeling and diastolic dysfunction, potentially attributed to its anti-inflammatory, anti-hypertrophic, and anti-fibrotic effects. These results provide a sound theoretical rationale for the clinical application of Sac/val in patients with HFpEF.

Targeting epicardial adipose tissue: A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various comorbidities, multiple cardiac and extracardiac pathophysiologic abnormalities, and diverse phenotypic presentations. Since HFpEF is a heterogeneous disease with different phenotypes, individualized treatment is required. HFpEF with type 2 diabetes mellitus (T2DM) represents a specific phenotype of HFpEF, with about 45%-50% of HFpEF patients suffering from T2DM. Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM, which is intimately related to the expansion and dysfunction (inflammation and hypermetabolic activity) of epicardial adipose tissue (EAT). EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms. Therefore, suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM. Although there is no treatment specifically for EAT, lifestyle management, bariatric surgery, and some pharmaceutical interventions (anti-cytokine drugs, statins, proprotein convertase subtilisin/kexin type 9 inhibitors, metformin, glucagon-like peptide-1 receptor agonists, and especially sodium-glucose cotransporter-2 inhibitors) have been shown to attenuate the inflammatory response or expansion of EAT. Importantly, these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF. Accordingly, well-designed randomized controlled trials are needed to validate the efficacy of current therapies. In addition, more novel and effective therapies targeting EAT are needed in the future.

Effect of Kuanxiong Aerosol () on Patients with Angina Pectoris: A Non-inferiority Multi-center Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris. METHODS: Block randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina. RESULTS: The 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01). CONCLUSIONS: KA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).

[Effect of Kuanxiong aerosol on coronary heart disease angina patients: a multicenter randomized controlled clinical study].

OBJECTIVE: To evaluate the anginal attack-relieving efficacy and safety of Kuanxiong Aerosol (KA) in patients with coronary heart disease (CHD). METHODS: A total of 780 patients confirmatively diagnosed as CHD angina from November 2011 to December 2012 in 13 medical centers in the mainland area were assigned to 2 groups by blocked randomization, the treatment group (376 cases) and the control group (374 cases). When the angina attacked, patients in the treatment group received sublingual spray three times, 0.6 mL each time, while those in the control group sublingually dissolved Nitroglycerin Tablet (NT), 0.5 mg each tablet. The effective rate of angina relief, efficacy of electrocardiogram (ECG), and the incidence of adverse reactions were observed. RESULTS: The 3 min and 5 min remission rates of angina attack were 53.72% (202/376) and 94.41% (355/376) in the treatment group, and 47.86% (179/374) and 90.64% (339/374) in the control group. The 95% confidence interval (CI) of the difference between the 2 groups of 3 min and 5 min remission rates of angina attacks were [(-1.84%, 12.32%) and (-1.33%, 6.85%) respectively, P > 0.05]. The total improvement rates of ST-T changes in the treatment group and the control group after treatment were 74.07% and 73.13% respectively (P > 0.05). The adverse reaction rate was 9.31 (35/376 cases) in the treatment group and 22.46% (84/374 cases) in the control group (P < 0.01). CONCLUSION: KA was not inferior to NT in relieving anginal attacks and improving ischemic ECG changes, and had obviously less adverse reaction.

[Application of patient-reported outcome in Chinese medical therapeutic efficacy assessment of cardiovascular diseases and some considerations on it].

Patient-reported outcome (PRO) is one of the important measures for clinical therapeutic efficacy assessment. The current application and development of PRO in China and abroad were introduced in this paper, put stress on the application of PRO in Chinese medical therapeutic efficacy assessment of cardiovascular diseases. Moreover, some suggestions on its further application were offered.

[Effects of water extractives of a qi and blood regulating prescription on early atherosclerosis of apolipoprotein E-deficient mice].

OBJECTIVE: To investigate whether the water extractives of regulating qi and blood prescription (WQBP) had effects on early atherosclerosis of apolipoprotein E-deficient mice (ApoE-mice) at the age of 19 weeks or not, and to explore the possible mechanisms. METHODS: Forty ApoE-mice, six weeks of age, were given high-fat diet and randomly divided into four groups: high-dose WQBP-treated group (360 mg/kg), low-dose WQBP-treated group (72 mg/kg), simvastatin-treated group (25 mg/kg) and untreated group, with ten mice in each group. Meanwhile, ten C57BL/6 mice of same genetic background were allocated to normal control group. Mice in the high- and low-dose WQBP-treated groups and simvastatin-treated group were administered with corresponding drugs from the 15 to 19 weeks. Mice in the untreated and normal control groups were administered with isovolumic water. Sacrificed at 19 weeks, the level of blood-lipid, the plaque construction, plaque integral, and the contents of plaque macrophages and vessel smooth muscle cells of the mice were analyzed by immunohistochemical method and a computer picture processing system. RESULTS: Compared to the untreated group, high-dose WQBP group could obviously decrease the level of low-density lipoprotein cholesterol (LDL-C). Simvastatin group could decrease the levels of LDL-C and total cholesterol (TC) (P<0.01). In high-dose WQBP-treated group and simvastatin-treated group, the thickness of fiber cap and the quantities of vessel smooth muscle cells increased (P<0.05), the quantities of plaque macrophages and the ratio of lipid and plaque reduced (P<0.01). CONCLUSION: WQBP and simvastatin can interfere in early atherosclerosis of ApoE-mice, attenuate and stabilize plaque in some extent. The mechanisms may include adjusting blood lipid, decreasing macrophage number and increasing the quantities of vessel smooth muscle cells.

[Effect of purified xuefu capsule on ultrasonographic figures in patients with carotid atherosclerosis].

OBJECTIVE: To investigate the effect of Purified Xuefu Capsule (PXC) on ultrasonographic figures in patients with carotid atherosclerosis (CAS). METHODS: Ninety-two patients with CAS were randomly divided into two groups, the 45 patients in the treated group were treated by conventional western medicine with additional PXC, the 47 patients in the control group were given conventional western medicine alone. One month's treatment was regarded as one course, and three courses of treatment were given successively to both groups. Carotid ultrasonography was performed before and after treatment, and the figures were compared. RESULTS: The thickness of endangium, average number of plaques, plaque scores, plaque volume index and length of the biggest soft plaque or mixed plaques, stenosis rate of vascular area, and the resistant index of blood vessels were decreased after treated with PXC for 3 months in the treated group. The differences of these indexes in the treated group before and after treatment, and that between the treated group and the control group after treatment were significant (P < 0.01). CONCLUSION: PXC can improve hemodynamics and eliminate atherosclerotic plaque to a certain degree, so it has definite effect for prevention and treatment of CAS.