Inflammatory Links Between Hypertriglyceridemia and Atherogenesis

Area of Science:

• Cardiovascular Science
• Metabolic Disorders
• Inflammation Research

Background:

• Hypertriglyceridemia (HTG), characterized by elevated triglyceride-rich lipoproteins (TGRL), is increasingly recognized as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD).
• The precise mechanisms linking HTG to ASCVD remain incompletely elucidated but involve complex interactions with inflammatory pathways.
• Triglyceride-rich lipoproteins and their remnants may play a more significant role in promoting inflammation and atherogenesis compared to low-density lipoproteins.

Purpose of the Study:

• To review the potential mechanisms connecting hypertriglyceridemia (HTG) and atherosclerotic cardiovascular disease (ASCVD) risk.
• To discuss the potential efficacy of therapies targeting HTG in the prevention of ASCVD.

Main Methods:

• This review synthesizes current clinical and preclinical evidence.
• It examines the role of inflammation in the atherogenic process associated with HTG.
• It evaluates emerging therapeutic strategies for HTG and inflammation.

Main Results:

• Elevated TGRL and their remnants contribute to ASCVD by penetrating the endothelium, promoting macrophage foam cell formation, and driving arterial wall inflammation.
• Lipid-laden foamy monocytes, derived from TGRL uptake, may infiltrate the arterial wall, further contributing to atherogenesis.
• Inflammation is a critical mediator in the causal relationship between HTG and ASCVD.

Conclusions:

• Hypertriglyceridemia (HTG) is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), with inflammation playing a central role in its pathogenesis.
• Novel therapeutic interventions targeting HTG and/or inflammation show promise in reducing the residual ASCVD risk associated with elevated triglyceride levels.