Triglyceride-glucose index's link to cardiovascular outcomes post-percutaneous coronary intervention in China: a meta-analysis.

Percutaneous coronary intervention (PCI) addresses myocardial ischaemia, but a significant subset of patients encounter major adverse cardiovascular events (MACE) post-treatment. This meta-analysis investigated the relationship between the post-PCI triglyceride-glucose (TyG) index and MACE. Comprehensive searches of the Embase, PubMed, Cochrane Library, and Web of Science databases were conducted up to 3 March 2023, using relevant keywords. The effect size was determined based on I2 statistic using random-effects models. Cluster-robust standard errors crafted the dose-response curve, and the GRADE Evaluation Scale was employed to rate the quality of evidence. The group with the highest TyG index had significantly higher post-PCI MACE rates than the lowest index group, with hazard ratios (HRs) of 2.04 (95% CI 1.65-2.52; I2 = 77%). Each unit increase in TyG index corresponded to HRs of 1.82 for MACE (95% CI 1.34-2.46; I2 = 92%), 2.57 for non-fatal MI (95% CI 1.49-4.41; I2 = 63%), and 2.06 for revascularization (95% CI 1.23-3.50; I2 = 90%). A linear relationship between TyG index and MACE risk was established (R2 = 0.6114). For all-cause mortality, the HR was 1.93 (95% CI 1.35-2.75; I2 = 50%), indicating a higher mortality risk with elevated TyG index. The GRADE assessment yielded high certainty for non-fatal MI but low certainty for all-cause mortality, revascularization, and MACE. The TyG index may predict risks of post-PCI MACE, all-cause mortality, non-fatal MI, and revascularization, with varied levels of certainty. A potential linear association between the TyG index and MACE post-PCI was identified. Future research should validate these findings.

Protective effects of paeoniflorin on cardiovascular diseases: A pharmacological and mechanistic overview.

Background and ethnopharmacological relevance: The morbidity and mortality of cardiovascular diseases (CVDs) are among the highest of all diseases, necessitating the search for effective drugs and the improvement of prognosis for CVD patients. Paeoniflorin (5beta-[(Benzoyloxy)methyl] tetrahydro-5-hydroxy-2-methyl-2,5-methano-1H-3,4-dioxacyclobuta [cd] pentalen-1alpha (2H)-yl-beta-D-glucopyranoside, C23H28O11) is mostly derived from the plants of the family Paeoniaceae (a single genus family) and is known to possess multiple pharmacological properties in the treatment of CVDs, making it a promising agent for the protection of the cardiovascular system. Aim of the study: This review evaluates the pharmacological effects and potential mechanisms of paeoniflorin in the treatment of CVDs, with the aim of advancing its further development and application. Methods: Various relevant literatures were searched in PubMed, ScienceDirect, Google Scholar and Web of Science. All eligible studies were analyzed and summarized in this review. Results: Paeoniflorin is a natural drug with great potential for development, which can protect the cardiovascular system by regulating glucose and lipid metabolism, exerting anti-inflammatory, anti-oxidative stress, and anti-arteriosclerotic activities, improving cardiac function, and inhibiting cardiac remodeling. However, paeoniflorin was found to have low bioavailability, and its toxicology and safety must be further studied and analyzed, and clinical studies related to it must be carried out. Conclusion: Before paeoniflorin can be used as an effective therapeutic drug for CVDs, further in-depth experimental research, clinical trials, and structural modifications or development of new preparations are required.

Polydatin protects against atherosclerosis by activating autophagy and inhibiting pyroptosis mediated by the NLRP3 inflammasome.

ETHNOPHARMACOLOGICAL RELEVANCE: Polydatin is a bioactive ingredient extracted from the roots of the Reynoutria japonica Houtt, and it is a natural precursor of resveratrol. Polydatin is a useful inhibitor of inflammation and acts as a regulator of lipid metabolism. However, the specific mechanisms of action of polydatin in atherosclerosis (AS) remains poorly explained. AIM OF THE STUDY: The aim of this study was to assess the efficacy of polydatin on inflammation induced by the inflammatory cell death and autophagy in AS. MATERIALS AND METHODS: Apolipoprotein E knockout (ApoE-/-) mice were fed with a high-fat diet (HFD) for 12 weeks to induce the formation of atherosclerotic lesions. The ApoE-/- mice were then randomly divided into the following six groups: (1) model group, (2) simvastatin group, (3) MCC950 group, (4) low dose polydatin group (Polydatin-L), (5) medium dose polydatin group (Polydatin-M), (6) and high dose polydatin group (Polydatin-H). The C57BL/6J mice were treated as controls and administered a standard chow diet. All mice were gavaged once daily for 8 weeks. The distribution of aortic plaques was observed by En Oil-red-O staining and hematoxylin and eosin staining (H&E). Oil-red-O staining was used to observe lipid content in the aortic sinus plaque; Masson trichrome staining was used to gauge collagen content in the plaque; and immunohistochemistry was used to evaluate smooth muscle actin (α-SMA) and CD68 macrophages marker expression levels in the plaque, which were used to assess the vulnerability index of the plaque. The lipid levels were measured using an enzymatic assay with an automatic biochemical analyzer. The level of inflammation was detected by enzyme-linked-immunosorbent assay (ELISA). Autophagosomes were detected by transmission electron microscopy (TEM). Pyroptosis was detected by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL)/caspase-1 and other proteins related to the expression levels of autophagy and pyroptosis were detected by Western blot analysis. RESULTS: Nucleotide oligomerization (NOD)-like receptor (NLR) family pyrin domain-containing protein 3 (NLRP3) inflammasome activation leads to pyroptosis, including the cleavage of caspase-1, interleukin (IL)-1ß and IL-18 production, and the co-expression of TUNEL/caspase-1-all of these are inhibited by polydatin, whose inhibitory effect is similar to that of MCC950, a specific inhibitor of NLRP3. Further, polydatin decreased the protein expression of NLRP3 and the phosphorylated mammalian target of rapamycin (p-mTOR), and increased the number of autophagosomes as well as the increased the cytoplasmic microtubule-associated protein light chain 3 (LC3)/autophagosome membrane-type LC3 ratio. Moreover, the protein expression levels of p62 decreased, suggesting that polydatin can increase autophagy. CONCLUSIONS: Polydatin can inhibit the activation of the NLRP3 inflammasome and cleavage of caspase-1, thereby inhibiting pyroptosis and secretion of inflammatory cytokines, and promoting autophagy through NLRP3/mTOR pathway in AS.

Effect of Different Types and Dosages of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Lipoprotein(a) Levels: A Network Meta-analysis.

ABSTRACT: Lipoprotein(a) [Lp(a)] has become an important component of the residual risk of cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors display promising effects in controlling Lp(a) levels. However, the effects of different types and dosages of PCSK9 inhibitors on Lp(a) have not been studied in detail. These include 2 monoclonal antibodies, alirocumab and evolocumab, and inclisiran, a small interfering RNA. We searched PubMed, Web of Science, Embase, and Cochrane Library for randomized controlled trials to investigate the efficacy of PCSK9 inhibitors at the Lp(a) level. Although changes in Lp(a) levels were not the primary endpoint in any of these studies, they all described these valuable data. Forty-one randomized controlled trials with 17,601 participants were included, involving 23 unduplicated interventions. Most PCSK9 inhibitors significantly reduced Lp(a) levels compared with placebo. The pairwise comparison demonstrated no significant difference among most PCSK9 inhibitors. However, in the comparison among different dosages of alirocumab, the dosage of 150 mg Q2W showed a significant reduction in Lp(a) levels compared with the dosages of 150, 200, and 300 mg Q4W. In addition, the comparison results demonstrated the significant efficacy of evolocumab 140 mg Q2W compared with alirocumab at a dosage of 150 mg Q4W. The cumulative rank probabilities demonstrated that evolocumab 140 mg Q2W showed the highest efficacy. This study showed that PCSK9 inhibitors reduced Lp(a) levels by up to 25.1%. A biweekly dose of either 140 mg evolocumab or 150 mg alirocumab was the best treatment option. However, the reduction in Lp(a) levels with a single kind of PCSK9 inhibitor alone did not demonstrate sufficient clinical benefit. Therefore, for patients with very high Lp(a) levels who remain at high residual risk in the context of statin administration, it may be acceptable to use a kind of PCSK9 inhibitor, but the clinical benefit needs further investigation.

Targets of statins intervention in LDL-C metabolism: Gut microbiota.

Increasing researches have considered gut microbiota as a new "metabolic organ," which mediates the occurrence and development of metabolic diseases. In addition, the liver is an important organ of lipid metabolism, and abnormal lipid metabolism can cause the elevation of blood lipids. Among them, elevated low-density lipoprotein cholesterol (LDL-C) is related with ectopic lipid deposition and metabolic diseases, and statins are widely used to lower LDL-C. In recent years, the gut microbiota has been shown to mediate statins efficacy, both in animals and humans. The effect of statins on microbiota abundance has been deeply explored, and the pathways through which statins reduce the LDL-C levels by affecting the abundance of microbiota have gradually been explored. In this review, we discussed the interaction between gut microbiota and cholesterol metabolism, especially the cholesterol-lowering effect of statins mediated by gut microbiota, via AMPK-PPARγ-SREBP1C/2, FXR and PXR-related, and LPS-TLR4-Myd88 pathways, which may help to explain the individual differences in statins efficacy.

Paeonol for the Treatment of Atherosclerotic Cardiovascular Disease: A Pharmacological and Mechanistic Overview.

With improvement in living standards and average life expectancy, atherosclerotic cardiovascular disease incidences and mortality have been increasing annually. Paeonia suffruticosa, a natural herb, has been used for the treatment of atherosclerotic cardiovascular disease for thousands of years in Eastern countries. Paeonol is an active ingredient extracted from Paeonia suffruticosa. Previous studies have extensively explored the clinical benefits of paeonol. However, comprehensive reviews on the cardiovascular protective effects of paeonol have not been conducted. The current review summarizes studies reporting on the protective effects of paeonol on the cardiovascular system. This study includes studies published in the last 10 years. The biological characteristics of Paeonia suffruticosa, pharmacological mechanisms of paeonol, and its toxicological and pharmacokinetic characteristics were explored. The findings of this study show that paeonol confers protection against atherosclerotic cardiovascular disease through various mechanisms, including inflammation, platelet aggregation, lipid metabolism, mitochondria damage, endoplasmic reticulum stress, autophagy, and non-coding RNA. Further studies should be conducted to elucidate the cardiovascular benefits of paeonol.

Loganin inhibits macrophage M1 polarization and modulates sirt1/NF-κB signaling pathway to attenuate ulcerative colitis.

Loganin, a major bioactive iridoid glycoside derived from Cornus officinalis, exerts different beneficial biological properties. Recently, loganin has been reported to exhibit potential anti-inflammatory effects in the intestinal tissues, while the detailed mechanisms remain elusive. This study aimed to investigate whether loganin could inhibit the inflammatory response in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and to explore possible molecular mechanisms involved in this process. Results showed that oral administration of loganin significantly decreased body weight loss, disease activity index, colon shortening, myeloperoxidase (MPO) activity and pathologic abnormalities in UC mice. Loganin obviously inhibited the mRNA and protein levels of IL-6, TNF-α and IL-1ß in colon tissues from UC mice. Furthermore, loganin remarkably reduced macrophage M1 polarization in UC mice evidenced by reduced the number of F4/80 and iNOS dual-stained M1 macrophages, and the expression of M1 macrophage-related pro-inflammatory chemokines/cytokines including MCP-1, CXCL10 as well as COX-2. Further investigation showed that loganin upregulated the mRNA and protein levels of Sirt1, with the inhibition of NF-κB-p65 acetylation in colon tissues from UC mice. Moreover, Sirt1-specific inhibitor Ex527 administration abolished the anti-inflammatory and anti-macrophage M1 polarization effects of loganin in UC. Thus, loganin could inhibit M1 macrophage-mediated inflammation and modulate Sirt1/NF-κB signaling pathway to attenuate DSS-induced UC. Loganin was considered as a viable natural strategy in the treatment of UC.[Figure: see text].