Title:The Role of Triglycerides in Atherosclerosis: Recent Pathophysiologic
Insights and Therapeutic Implications
Volume: 20
Issue: 2
Author(s): Yonatan Akivis*, Hussam Alkaissi, Samy I. McFarlane and Inna Bukharovich
Affiliation:
- Department of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, 11203, USA
Keywords:
Triglycerides, atherosclerosis, cardiovascular disease, lipoprotein metabolism, hypertriglyceridemia, metabolic syndrome, insulin resistance.
Abstract:
Triglycerides have long been recognized as a cardiovascular disease risk factor. However,
their precise role in atherosclerosis and potential utility as a therapeutic target remains debated
topics. This review aims to shed light on these aspects by exploring the complex relationship
between triglycerides and atherosclerosis from pathophysiological and pharmacological
perspectives.
Triglycerides, primarily carried by chylomicrons and very low-density lipoproteins, play an essential
role in energy storage and utilization. Dysregulation of triglyceride homeostasis and triglyceride-
rich lipoproteins metabolism often leads to hypertriglyceridemia and subsequently increases
atherosclerosis risk. Triglyceride-rich lipoproteins remnants interact with arterial wall
endothelial cells, get retained in the subendothelial space, and elicit inflammatory responses,
thereby accelerating atherogenesis.
Despite the clear association between high triglyceride levels and increased cardiovascular disease
risk, intervention trials targeting triglyceride reduction have produced mixed results. We
discuss a range of triglyceride-lowering agents, from fibrates to omega-3 fatty acids, with a focus
on their mechanism of action, efficacy, and major clinical trial outcomes. Notably, the role
of newer agents, such as angiopoietin-like protein 3 and apolipoprotein C3 inhibitors, is also explored.
We highlight the challenges and controversies, including the ongoing debate on the causal role
of triglyceride in atherosclerosis and the discordant outcomes of recent clinical trials. The potential
confounding effects of associated risk factors, such as elevated apolipoprotein B, insulin resistance,
and metabolic syndrome, are considered.
In conclusion, this review underscores the importance of a nuanced approach to understanding
the role of triglycerides in atherosclerosis and their potential as a therapeutic target. Further research
is needed to unravel the complex interplay between triglycerides, triglyceride-rich lipoproteins,
and associated factors in atherosclerosis pathogenesis and refine triglyceride-targeted
therapeutic strategies.
