Serum carboxymethyl lysine and atherosclerosis
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Serum Carboxymethyl Lysine (CML) as a Biomarker in Atherosclerosis
Serum carboxymethyl lysine (CML) is an advanced glycation end product (AGE) that has been widely studied for its role in atherosclerosis and cardiovascular disease. Research consistently shows that CML levels are elevated in patients with coronary heart disease (CHD) and are associated with the severity of atherosclerosis Ding2000Liu2022Nerlich1999+4 MORE.
CML Levels and Atherosclerosis Severity
Multiple studies have found that serum CML concentrations are significantly higher in individuals with CHD compared to healthy controls. The increase in CML is even more pronounced in patients with both hypertension and CHD Ding2000Liu2022. Furthermore, the degree of atherosclerosis, as measured by clinical scoring systems, correlates positively with serum CML levels—higher CML is linked to more severe atherosclerotic disease Liu2022Nerlich1999Nogami2020+1 MORE.
CML Accumulation in Vascular Tissue
Immunohistochemical studies reveal that CML accumulates in the arterial walls, especially in older adults and those with atherosclerosis. The accumulation is most notable in the extracellular matrix and within macrophages in atherosclerotic plaques, suggesting a role for CML in local oxidative stress and plaque development Nerlich1999Schleicher1997Nogami2020. The presence of CML in arterial tissue increases with age and is further accelerated in diabetes and atherosclerosis Nerlich1999Schleicher1997Nogami2020.
Mechanisms Linking CML to Atherosclerosis
CML contributes to atherosclerosis through several mechanisms. It can modify low-density lipoprotein (LDL), making it more likely to be taken up by scavenger receptors on macrophages and smooth muscle cells, which promotes foam cell formation and plaque buildup Wang2019Ahmed2008. CML also induces foam cell apoptosis by inhibiting the PI3K/Akt signaling pathway, which may contribute to plaque instability and progression of atherosclerosis, particularly in diabetes . Additionally, CML is associated with increased arterial stiffness and hypertension, both of which are risk factors for atherosclerosis .
Diagnostic and Clinical Implications
Serum CML, along with related markers such as sRAGE and esRAGE, can effectively indicate the presence and severity of atherosclerosis in CHD patients. Combined measurement of these markers improves diagnostic sensitivity and specificity for severe atherosclerosis . CML immunoreactivity in heart vessels also correlates with other markers of cardiovascular disease, such as NT-proBNP and the degree of cardiac fibrosis, supporting its use in cardiovascular risk assessment .
Limitations and Specificity
While CML is a strong marker for atherosclerosis and related vascular changes, its association with peripheral artery disease is less clear, as some studies have not found a significant relationship in older adults . This suggests that the role of CML may vary depending on the vascular bed and patient population.
Conclusion
Elevated serum carboxymethyl lysine is closely linked to the presence and severity of atherosclerosis, particularly in coronary heart disease and in individuals with diabetes or hypertension. CML serves as a useful biomarker for oxidative stress, arterial stiffness, and plaque progression, and its measurement can aid in the diagnosis and management of atherosclerotic cardiovascular disease Ding2000Liu2022Nerlich1999+5 MORE.
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