Plasminogen Regulation in Atherosclerotic Disease

Plasminogen, the zymogen precursor of the serine protease plasmin, occupies a central role in the balance between fibrin deposition and degradation within the vessel wall. Upon activation by tissue‐type or urokinase‐type plasminogen activators, plasmin cleaves fibrin matrices and modulates extracellular matrix turnover, thereby influencing plaque stability and vascular remodelling. Beyond its fibrinolytic functions, plasminogen and its cleavage products regulate inflammatory cell recruitment, smooth muscle cell migration and lipoprotein handling by macrophages. Dysregulated plasminogen activation can tip the balance towards either excessive fibrin retention—promoting thrombus formation on vulnerable plaques—or excessive proteolysis, which may weaken the fibrous cap. A comprehensive understanding of plasminogen modulation has thus emerged as a critical axis in atherogenesis, linking haemostasis, lipid metabolism and immune‐mediated clearance processes to the development, progression and complication of atherosclerotic lesions.

Research from Nature Portfolio

Recent studies have characterised the heterogeneity of monocyte‐derived macrophages within human coronary lesions, revealing subpopulations with differential efferocytic capacity and pro‐thrombotic marker expression. In individuals with advanced coronary artery disease, macrophages adopt a rounded morphology associated with impaired clearance of apoptotic debris and elevated levels of tissue factor. This skewed phenotype correlates with thinner fibrous caps, lipid‐rich cores and a higher incidence of plaque rupture. Such findings underscore how the local balance of proteolytic activities, including plasmin‐mediated fibrin clearance, interplays with macrophage function to determine plaque vulnerability and patient risk stratification.

Plasminogen Regulation in Atherosclerotic Disease publication trend

The graph below shows the total number of articles in plasminogen regulation in atherosclerotic disease across all publications each year (not limited to Nature Index journals).

Technical terms

Plasminogen: Inactive precursor of plasmin, circulating in plasma and binding to fibrin or cell surfaces prior to activation.

Plasmin: Active serine protease that degrades fibrin clots and extracellular matrix proteins.

Tissue‐type plasminogen activator (tPA): Endothelial‐derived enzyme that converts plasminogen to plasmin on fibrin surfaces.

Efferocytosis: Phagocytic clearance of apoptotic cells by macrophages, essential for resolution of inflammation within plaques.

Tissue factor: Transmembrane glycoprotein that initiates the coagulation cascade and may localise with macrophages in vulnerable plaques.

Foam cells: Lipid‐laden macrophages formed by uptake of modified low‐density lipoproteins, contributing to plaque growth.

References

1. Biological profile of monocyte-derived macrophages in coronary heart disease patients: implications for plaque morphology. Scientific Reports (2019).
2. Plasminogen Deficiency Significantly Reduces Vascular Wall Disease in a Murine Model of Type IIa Hypercholesterolemia. Biomedicines (2021).
3. Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen Activator. Frontiers in Physiology (2019).