A Novel Mechanism Links Lipoprotein(a) to Blood Clotting in the Arteries and Increased Risk of Heart Attack
Mount Sinai-led study leads to improved understanding of risk
Journal: Journal of Lipid Research – May 2025
https://www.jlr.org/article/S0022-2275(25)00080-X/fulltext
Author: Robert S. Rosenson, MD, Director of Metabolism and Lipids at the Icahn School of Medicine of Mount Sinai
Bottom line of study: High lipoprotein(a) or Lp(a) in patients with coronary artery disease carry and express more tissue factor (the key regulator of blood clotting from the arterial wall) on their monocytes and express more tissue factor on their monocytes. The tissue factor in patients with high Lp(a) activates blood clotting, which can lead to a heart attack.
Why the study is unique? This is the first study to demonstrate a link between inflammation from circulating monocytes and tissue factor production, expression, and function.
Why the study is important? Many patients with high Lp(a) levels have an acute myocardial infarction as the first manifestation of cardiovascular disease. This is a thrombotic event that has been attributed incorrectly to impaired clot dissolution by apolipoprotein – apo(a). However, those studies separated the apo(a) from the intact molecule and may not have relevance. Further, patients with high Lp(a) do not have higher rates of venous clots in the legs or pulmonary emboli.
How was the research conducted? Researchers performed proteomic, transcriptomic, and functional biology studies on blood collected from 64 patients with coronary artery disease.
Results: High versus low Lp(a) levels were associated with significantly elevated markers of inflammation and vascular dysfunction. One of these vascular markers was tissue factor present on the circulating monocytes, a type of white blood cells that enter the arterial wall and participated in plaque formation. The mononuclear cells of patients with high Lp(a) levels also expressed more tissue factor through a specific receptor-mediated pathway. Importantly, the tissue factor was functional in that it accelerated the conversion of protein Factor X to Factor Xa, an activated clotting factor that promotes blood clotting.
What the study means for patients? This study provides insights into the reason that many patients have an acute myocardial infarction as their first manifestation of cardiovascular disease. The importance of the tissue factor pathway may allow for better refinement of cardiovascular risk in patients with high Lp(a).
What the study means for clinicians? This study provides insights into the basis for the arterial thrombi or blood clots that occur in patients with high Lp(a), and provides a framework for studies to more completely and accurately identify the highest risk patients.
Project Co-principal investigator: Sascha N. Goonewardena, MD, Division of Cardiovascular Medicine, University of Michigan
Quotes:
“This newly defined mechanism contributes to a better understanding of blood clotting in coronary heart disease patients,” says Dr. Rosenson. “Linking Lp(a) to immune-mediated blood clotting enhances understanding of high-risk status for patients with high Lp(a) and can better inform clinical trial design and study populations to account for risk associated with Lp(a) and tissue factor to help save lives.”
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