Clinically relevant plasma proteome for adiposity depots: evidence from systematic mendelian randomization and colocalization analyses DOI Creative Commons
Min Cao, Bin Cui

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 13, 2024

Abstract Background The accumulation of visceral and ectopic fat comprise a major cause cardiometabolic diseases. However, novel drug targets for reducing unnecessary are still limited. Our study aims to provide comprehensive investigation the causal effects plasma proteome on using Mendelian randomization (MR) approach. Methods We performed two-sample MR analyses based five large genome-wide association (GWAS) summary statistics 2656 proteins, screen associations these proteins with traits in over 30,000 participants European ancestry, as well assess mediation by risk factors outcomes. colocalization analysis was conducted examine whether identified outcomes shared casual variants. Results Genetically predicted levels 14 circulating were associated ( P < 4.99 × 10 − 5 , at Bonferroni-corrected threshold). Colocalization prioritized ten protein that showed effect outcomes, including FST, SIRT2, DNAJB9, IL6R, CTSA, RGMB, PNLIPRP1, FLT4, PPY IL6ST. revealed seven 0.0024). Furthermore, DNAJB9 IGFBP1 primary mediated HDL-C SHBG. Sensitivity little evidence pleiotropy. Conclusions candidate showing putative potential therapeutic outlined pathways further prevention downstream

Language: Английский

Effects of Zofenopril on Arterial Stiffness in Hypertension Patients DOI Creative Commons
Benjamin Palić,

Ivica Brizić,

Emina Karahmet Sher

et al.

Molecular Biotechnology, Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 13, 2023

Abstract Angiotensin-converting enzyme inhibitors (ACEIs) reduce arterial stiffness beyond their antihypertensive effect. Studies showed that sulfhydryl ACEIs have the antioxidative potential to improve endothelial function, which might a clinical effect on distensibility. However, there are no studies directly compare effects of (zofenopril) and non-sulfhydryl (enalapril) stiffness. Therefore, this prospective study aims enalapril zofenopril oxidative stress in both short- long-term treatment hypertension (AH). Baseline post-treatment peripheral central pressure indices, augmentation index (Aix), aortic pulse wave velocity (ao-PWV), serum levels oxidized low-density cholesterol lipoprotein, LDL uric acid (UA) were measured. The results acute with zofenopril, contrast enalapril, significantly decreased Aix (p < 0.001). Chronic superior over reduction systolic ao-PWV = 0.004), as well 0.021) 0.021). indicates has beneficial compared enalapril. It potent efficacy AH further should its safety other drugs would aid clinicians treating various cardiovascular diseases common denominator.

Language: Английский

Citations

6
Association of visceral fat area or BMI with arterial stiffness in ideal cardiovascular health metrics among T2DM patients DOI Creative Commons
Ling Zhao,

Xiangming Zhou,

Yufei Chen

et al.

Journal of Diabetes, Journal Year: 2023, Volume and Issue: 16(1)

Published: Sept. 8, 2023

Abstract Background “Obesity paradox” occurs in type 2 diabetes mellitus (T2DM) patients when body mass index (BMI) is applied to define obesity. We examined the association of visceral fat area (VFA) as an obesity measurement with arterial stiffness seven ideal cardiovascular health metrics (ICVHMs). Methods A total 29 048 were included analysis from June 2017 April 2021 10 sites National Metabolic Management Centers. ICVHMs modified recommendations American Heart Association. Brachial‐ankle pulse wave velocity (BaPWV) ≥ 1400 cm/s was employed evaluate increased stiffness. Multivariate regression models used compare different effects BMI and VFA on Results Lower more strongly associated low BaPWV than lower other (adjusted odds ratio [OR], 0.85 [95% confidence interval [CI], 0.80–0.90] vs OR 1.08 CI, 1.00–1.17]). Multivariable‐adjusted ORs for highest VAT range 150‐200 cm OR, 1.26 CI 1.12–1.41]). Compared participants < 100 , among higher VFA, decreased gradually 1.89 (95% 1.73–2.07) who had ≤1 ICVHM 0.39 0.25–0.62) ≥5 ICVHMs. Conclusion In T2DM, using anthropometric measures obesity, relevant risk For describe would be optimal BMI.

Language: Английский

Citations

3
Clinically relevant plasma proteome for adiposity depots: evidence from systematic mendelian randomization and colocalization analyses DOI Creative Commons
Min Cao, Bin Cui

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 13, 2024

Abstract Background The accumulation of visceral and ectopic fat comprise a major cause cardiometabolic diseases. However, novel drug targets for reducing unnecessary are still limited. Our study aims to provide comprehensive investigation the causal effects plasma proteome on using Mendelian randomization (MR) approach. Methods We performed two-sample MR analyses based five large genome-wide association (GWAS) summary statistics 2656 proteins, screen associations these proteins with traits in over 30,000 participants European ancestry, as well assess mediation by risk factors outcomes. colocalization analysis was conducted examine whether identified outcomes shared casual variants. Results Genetically predicted levels 14 circulating were associated ( P < 4.99 × 10 − 5 , at Bonferroni-corrected threshold). Colocalization prioritized ten protein that showed effect outcomes, including FST, SIRT2, DNAJB9, IL6R, CTSA, RGMB, PNLIPRP1, FLT4, PPY IL6ST. revealed seven 0.0024). Furthermore, DNAJB9 IGFBP1 primary mediated HDL-C SHBG. Sensitivity little evidence pleiotropy. Conclusions candidate showing putative potential therapeutic outlined pathways further prevention downstream

Language: Английский

Citations

0