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- Huang, Wuqing, et al.
(författare)
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PDE5 inhibition mitigates heart failure in hyperlipidemia
- 2024
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Ingår i: Biomedicine and Pharmacotherapy. - 0753-3322. ; 175
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Tidskriftsartikel (refereegranskat)abstract
- PDE5 inhibitors was reported to play a protective role in both regulating lipid metabolism and reducing heart failure (HF). This study aimed to clarify the effectiveness of PDE5 inhibitors against hyperlipidemia-related HF by combining evidence from population-based study and animal models. The nationwide cohort study found that post-diagnostic use of PDE5 inhibitors was associated with a significantly lower risk of HF compared with patients who used alprostadil, especially among individuals with hyperlipidemia (adjusted HR = 0.56, 95% CI = 0.40–0.78). In animal models, sildenafil significantly recovered the cardiac structure and function induced by AAB surgery, as well as reversed liver dysfunction and ameliorated hyperlipidemia induced by HFD via reducing the level of ALT, AST and serum lipids. Lipidomic analysis identified four lipid metabolites involved in sildenafil administration, including FA 16:3, LPC O-18:1, DG24:0_18:0 and SE28:1/20:4. This study revealed the protective effect of PDE5 inhibitors against HF in hyperlipidemia, indicating the potential of being repurposed as an adjuvant for HF prevention in patients with hyperlipidemia if these findings can be further confirmed in clinical trials.
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| 2. |
- Xiao, Jun, et al.
(författare)
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Association of genetically-predicted lipid traits and lipid-modifying targets with heart failure
- 2023
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 30:4, s. 358-366
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To assess the association of genetically-predicted lipid traits and lipid-modification via licensed or investigational targets with heart failure (HF).METHODS AND RESULTS: Two-sample Mendelian randomization (MR) study was conducted using summary-level genome-wide association studies (GWASs) from UK Biobank and HERMES Consortium. Genetic variants obtained from UK Biobank GWAS data were selected as instrumental variables to predict the level of lipid traits (low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (ApoB) and apolipoprotein AI (ApoAI)) and lipid-modifying effect of eight drug targets (HMGCR, PCSK9, NPC1L1, PPARA, LPL, ANGPTL3, APOC3 and CETP). In this study, we observed that genetically-predicted LDL-C, TG, HDL-C or ApoB were significantly related to HF, which were mainly mediated by CHD. Drug target MR analyses identified PCSK9, CETP and LPL as potential targets to prevent HF. The genetic proxy of LDL-C and ApoB increase modified by PCSK9 showed similar evidence in increasing risk of HF (PLDL-C = 1.27*10-4; PApoB = 1.94*10-4); CETP played a role in HF risk via modifying all investigational lipid traits with the strongest evidence though ApoB (P = 5.87*10-6); LPL exerted effects on HF via modifying most lipid traits with the strongest evidence observed via modifying TG (P = 3.73*10-12).CONCLUSION: This two-sample MR study provided genetic evidence of the associations between lipid traits and HF risk, which were mostly mediated by CHD. Besides, drug target MR studies indicated that PCSK9 inhibition, CETP inhibition and LPL activation were effective in HF reduction.FUNDING INFORMATION: Start-up Fund for high-level talents of Fujian Medical University.
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