ArticleAmerican journal of physiology. Heart and circulatory physiology2024
Relationship between LDL-cholesterol, small and dense LDL particles, and mRNA expression in a cohort of African Americans.
Article in American journal of physiology. Heart and circulatory physiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Superior prognostic value of estimated small dense LDL cholesterol for cardiovascular risk assessment: evidence from international cohort studies.Lipids in health and disease · 2025Article
- Regulatory Roles of Long Noncoding RNAs in Arterial Stiffness and Hypertension.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Intersecting transcriptomic landscapes of hypertension and kidney function in African American women.American journal of physiology. Renal physiology · 2025Article
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Authors and funding
5 authors.
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Abstract
Understanding the characteristics and behavior of low-density lipoprotein (LDL) particles provides insights into the atherogenic risk of elevated LDL cholesterol in hypercholesterolemia, cardiovascular disease risks. Studying LDL particles helps identify specific LDL subtypes [e.g., small dense LDL particles (sdLDL)] that may be atherogenic and, consequently, potential targets for therapeutics. This study cohort consists of African Americans (AAs), a population disproportionately affected by cardiovascular diseases, thereby accentuating the importance of the investigation. Differential expression (DE) analysis was undertaken using a dataset comprising 17,947 protein-coding mRNAs from the whole blood transcriptomes of 416 samples to identify mRNAs associated with low-density lipoprotein cholesterol (LDL-C) and sdLDL plasma levels. Subsequently, mediation analyses were used to investigate the mediating role of sdLDL particles on the relationship between LDL-C levels and mRNA expression. Finally, pathway enrichment analysis was conducted to identify pathways involving mRNAs whose relationship with LDL-C is mediated by sdLDL. DE analysis revealed 1,048 and 284 mRNA transcripts differentially expressed by LDL-C and sdLDL levels, respectively. Mediation analysis revealed that the associations between LDL-C and 33 mRNAs were mediated by sdLDL. Of the 33 mRNAs mediated by sdLDL, 18 were mediated in both males and females. Nine mRNAs were mediated only in females, and six were mediated only in males. Pathway analysis showed that 33 mRNAs are involved in pathways associated with the immune system, inflammatory response, metabolism, and cardiovascular disease (CVD) risk. In conclusion, our study provides valuable insights into the complex interplay between LDL-C, sdLDL, and mRNA expression in a large sample of AAs. The results underscore the importance of incorporating sdLDL measurement alongside LDL-C levels to improve the accuracy of managing hypercholesterolemia and effectively stratify the risk of CVD. This is essential as differences in sdLDL modulate atherogenic properties at the transcriptome level.
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