Hyperlipidemia is a common metabolic disorder and one of risk factors for cardiovascular disease. Clinical studies have shown that hyperlipidemia increases the risk of non-ischemic heart failure, while decreasing serum lipids can reverse heart dysfunction. Apart from indirectly affecting the function of the heart by promoting the development of atherosclerosis, hyperlipidemia also affects the systolic function and cardiac electrophysiological response of the heart directly, which may be related to gradual accumulation of cardiac lipids and consequent systemic oxidative stress, proinflammatory state and mitochondrial dysfunction. However, the mechanism underlying direct effects of hyperlipidemia on the heart are not fully understood. In this review, we provide an updated summary of recent experimental and clinical studies that focus on elucidating the mechanisms of the action of hyperlipidemia on cardiac function, the relationship between heart failure and serum lipids, and protective effects of lipid-lowering drugs on the heart. The exciting progress in this field supports the prospect of guiding early protection of the heart to benefit the patients with chronic hyperlipidemia and familial hyperlipidemia.

/pdf/mechanisms-underlying-direct-actions-of-hyperlipidemia-on-562dl7f49j.pdf

Mechanisms underlying direct actions of hyperlipidemia on myocardium: An updated review

https://espace.library.uq.edu.au/view/UQ:dffe82f/UQdffe82f_OA.pdf

Danhong injection in cardiovascular and cerebrovascular diseases: Pharmacological actions, molecular mechanisms, and therapeutic potential.

https://doi.org/10.1016/j.apsb.2023.02.005

The traditional Chinese medicines treat chronic heart failure and their main bioactive constituents and mechanisms

Astragaloside IV (AGS IV) is the most important bioactive constituent of Radix Astragali. However, its disappointing clinical application is mainly caused by its very low solubility in biologic fluids, resulting in poor bioavailability after oral administration. We recently obtained a novel water-soluble derivative of AGS IV (astragalosidic acid, LS-102) that displayed significant cardioprotective potential against hypoxia-induced injury. The objective of this study was to investigate the intestinal absorption, main pharmacokinetic parameters and acute toxicity of LS-102 in rodents compared with AGS IV. An oral dose of LS-102 and AGS IV (20 mg/kg) was administered to Sprague-Dawley (SD) rats, and blood samples were collected at predetermined time points. The plasma concentrations were detected by a validated UHPLC-MS/MS method, and pharmacokinetic parameters were calculated using a compartmental model. In the intestinal permeability study, the transport of LS-102 across Caco-2 cell monolayers was investigated at six concentrations from 6.25 to 250 µM. Moreover, the acute toxicity of LS-102 (40–5000 mg/kg) via a single oral administration was investigated in BALB/c mice. LS-102 was rapidly absorbed, attaining a maximum concentration of 248.7 ± 22.0 ng/ml at 1.0 ± 0.5  h after oral administration. The relative bioavailability of LS-102 was twice that of AGS IV. LS-102 had a Papp (mean) of 15.72–25.50 × 10−6 cm/s, which was almost 500-fold higher than that of AGS IV, showing that LS-102 had better transepithelial permeability and could be better absorbed in the intestinal tract. The acute toxicity study showed no abnormal changes or mortality in mice treated with LS-102 even at the single high dose of 5000 mg/kg body weight. Oral LS-102 produced a pharmacokinetic profile different from AGS IV with higher bioavailability, while the toxic tolerance was similar to previous estimates. Thus, we speculated that LS-102 might provide better clinical efficacy and be a potential candidate for the new drug development of Radix Astragali.

Pharmacokinetics Comparison, Intestinal Absorption and Acute Toxicity Assessment of a Novel Water-Soluble Astragaloside IV Derivative (Astragalosidic Acid, LS-102)

Meta-analyses of randomized controlled trials (RCTs) have shown the beneficial effect of exercise on HDL-cholesterol (HDL-C) levels. However, systematic reviews are not free of bias, and this could call into question their results. The aim of this work was to conduct a critical assessment of meta-analyses of RCTs that analyze the association between exercise and HDL-C levels, evaluating their results and the risk of bias (RoB). This systematic review of MEDLINE and EMBASE included meta-analyses of RCTs that studied the effects of exercise on HDL-C levels in healthy adults or patients at cardiovascular risk. The RoB was determined using AMSTAR-2, and information was obtained on exercise and the variation in HDL-C levels. Twenty-three meta-analyses were included. Great variability was found in exercise (different types, frequencies or intensities in the studied interventions). All the analyses found an improvement in HDL-C levels, ranging from 0.27 to 5.41 mg/dl, in comparison with the control group (no exercise). The RoB was very high, with 18 reviews obtaining a critically low confidence level and the remaining works obtaining the highest confidence level. Only one meta-analysis showed good quality, in which HDL-C levels increased by 3.09 mg/dl in healthy adults and patients at high cardiovascular risk who practiced yoga. The rest had high RoB. Therefore, new systematic reviews with low RoB are needed to apply the results to clinical practice. Register: CRD42020158471 (PROSPERO).

Which Physical Exercise Interventions Increase HDL-Cholesterol Levels? A Systematic Review of Meta-analyses of Randomized Controlled Trials.

Dyslipidaemia is a major risk factor for coronary heart disease (CHD). Danhong and Huangqi injections, two traditional Chinese medicine prescriptions, have been widely studied regarding their lipid-lowering properties. However, the results were inconsistent and inconclusive. Thus, we conducted this meta-analysis of clinical controlled trials to clarify the lipid-lowering effects of Danhong and Huangqi injections. The databases including PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang Database, CNKI and VIP were searched. The following information was obtained from each study: first author, age, gender, ethnicity, health condition, treatment dose, treatment duration, sample size, mean and standard deviation or standard error of lipid variables before and after treatment. The changes in lipid levels from pre- to post-treatment were calculated and compared between the control groups and the treatment groups in this meta-analysis. Forty-four studies (5021 subjects) and 7 studies (542 subjects) were respectively identified for Danhong and Huangqi injections. Compared with the control groups, Danhong injection yielded a significant reduction in triglycerides (TG) [standardized mean difference (SMD) = − 0.76, 95% confidence interval (CI) = (− 0.91, − 0.61), P <  0.001], total cholesterol (TC) [SMD = − 1.29, 95% CI = (− 1.56, − 1.03), P <  0.001] and low-density lipoprotein cholesterol (LDL-C) [SMD = − 0.76, 95% CI = (− 0.93, − 0.59), P <  0.001], and a significant elevation in high-density lipoprotein cholesterol (HDL-C) [SMD = 0.70, 95% CI = (0.41, 0.98), P <  0.001]. Regarding Huangqi injection, it yielded a significant reduction in TC [SMD = − 1.13, 95% CI = (− 2.09, − 0.16), P = 0.02] and marginally in TG [SMD = − 1.27, 95% CI = (− 2.53, 0.00), P = 0.05] comparing with the control groups. Danhong injection can effectively decrease the plasma levels of TG, TC and LDL-C, and increase HDL-C levels. Huangqi injection also has significant effects on TG and TC reduction, but not as powerful as Danhong injection.

/pdf/the-lipid-lowering-effects-of-danhong-and-huangqi-injections-1s8oqwj9sy.pdf

The lipid-lowering effects of Danhong and Huangqi injections: a meta-analysis of clinical controlled trials

Objective To explore the possible effects of the microRNA(miR)-143/145 polymorphisms on cardiovascular risk factors and the severity of coronary heart disease(CHD) in Chinese Han people. Methods Polymerase chain reaction-restriction fragment length polymorphism analysis was employed to identify the genotypes of the rs353292 and rs4705343 polymorphisms for 380 patients with CHD and 163 CHD-free controls. The physiological and biochemical parameters between the genotypes were compared in the CHD patients and in controls,and the incidence of myocardial infarction(MI) was also compared between the genotypes in the CHD patients. Results The subjects with the rs353292 TT genotype had higher serum levels of triglycerides(F=3.00,P=0.05) and glucose(F=9.91,P<0.001) than the C carriers,and the subjects with the rs4705343 TT genotype had significantly higher prevalence of hypertension(Χ2=6.35,P=0.04) than the C carriers in the control group. The patients with the rs353292 TT genotype had significantly higher serum levels of hypersensitive C-reactive protein(hs-CRP)(F=8.43,P<0.001) than the C carriers in the CHD group,and the frequency of MI was significantly higher in the patients with the rs353292 TT genotype than that in the C carrier patients(Χ2=5.29,P=0.02). Conclusion The T allele of the rs353292 polymorphism is associated with serum hs-CRP levels in CHD patients,and it may affect the occurrence and development of MI by up-regulation of CRP gene through miR-143/145. The rs4705343 polymorphism is not related to the risk and severity of CHD.

[Associations of the MicroRNA-143/145 Polymorphisms with Cardiovascular Risk Factors and the Severity of Coronary Heart Disease].

The associations of the apolipoprotein B gene (APOB) rs693 and rs17240441 polymorphisms with plasma levels of APOB and lipids have been widely explored, but the results were inconclusive. This meta-analysis aimed to clarify the associations of the rs693 and rs17240441 polymorphisms with fasting APOB and lipid levels. Sixty-one studies (50,018 subjects) and 23 studies (8425 subjects) were respectively identified for the rs693 and rs17240441 polymorphisms by searching in PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang, VIP and CNKI databases. The following information was collected for each study: first author, age, gender, ethnicity, health condition, sample size, genotyping, lipid assay method, mean and standard deviation or standard error of APOB and lipid variables by genotypes. A dominant model was used for this meta-analysis. The carriers of the rs693 variant allele (T) had higher levels of APOB [standardized mean difference (SMD) = 0.26, 95% confidence interval (CI) = 0.16–0.36, P < 0.01], triglycerides (TG) (SMD = 0.12, 95% CI = 0.05–0.20, P < 0.01), total cholesterol (TC) (SMD = 0.24, 95% CI = 0.17–0.30, P < 0.01) and low-density lipoprotein cholesterol (LDL-C) (SMD = 0.22, 95% CI = 0.14–0.30, P < 0.01), and lower levels of high-density lipoprotein cholesterol (HDL-C) (SMD = −0.06, 95% CI = −0.11–0.01, P = 0.01) than the non-carriers. The carriers of the rs17240441 deletion allele had higher levels of APOB (SMD = 0.13, 95% CI = 0.06–0.20, P < 0.01), TC (SMD = 0.17, 95% CI = 0.07–0.26, P < 0.01) and LDL-C (SMD = 0.15, 95% CI = 0.07–0.23, P < 0.01) than the non-carriers. The rs693 polymorphism is significantly associated with higher levels of APOB, TG, TC and LDL-C, and lower levels of HDL-C. The rs17240441 polymorphism is significantly associated with higher levels of APOB, TC and LDL-C. Further studies are needed to elucidate the underlying mechanisms.

/pdf/associations-of-the-apob-rs693-and-rs17240441-polymorphisms-8ouo768xi8.pdf

Associations of the APOB rs693 and rs17240441 polymorphisms with plasma APOB and lipid levels: a meta-analysis.

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The lipid-lowering effects of Danhong and Huangqi injections: a meta-analysis of clinical controlled trials

[Associations of the MicroRNA-143/145 Polymorphisms with Cardiovascular Risk Factors and the Severity of Coronary Heart Disease].

Associations of the APOB rs693 and rs17240441 polymorphisms with plasma APOB and lipid levels: a meta-analysis.