A lower sCD146 concentration is independently associated with PAD, and an inverse relationship was observed between HDL-C and sCD146 in PAD patients, suggesting that sCD146 may reflect impaired endothelial homeostasis and metabolic dysregulation in PAD.
Key Findings
Results
Plasma soluble CD146 levels were significantly lower in PAD patients compared to healthy controls.
Mean sCD146 in PAD patients was 288 ng/mL (95% CI: 269–306) versus 480 ng/mL (95% CI: 460–500) in controls.
The difference was highly statistically significant (p < 0.0001).
Study included 184 Caucasian men with symptomatic PAD compared to 163 age-matched healthy control patients.
PAD diagnosis was confirmed using ankle-brachial index (ABI) and imaging.
Plasma sCD146 was quantified using ELISA.
Results
Each 10 ng/mL decrease in sCD146 was independently associated with increased odds of PAD after multivariable adjustment.
Age-adjusted odds ratio (OR) for PAD per 10 ng/mL decrease in sCD146 was 1.17 (95% CI: 1.13–1.22).
After adjustment for cardiovascular risk factors, the OR increased to 1.25 (95% CI: 1.14–1.36, p < 0.0001).
Associations were analyzed through multivariable logistic regression models.
The increasing OR after risk factor adjustment indicates sCD146 association with PAD is independent of traditional risk factors.
Results
sCD146 was not associated with PAD severity as measured by Fontaine stage.
Fontaine staging was used to classify PAD severity.
No statistically significant association was found between sCD146 levels and Fontaine stage categories.
This suggests sCD146 may be a marker of PAD presence rather than a graded marker of disease progression.
Results
The relationship between sCD146 and HDL cholesterol (HDL-C) was opposite in direction between PAD patients and healthy controls.
In controls, sCD146 was positively correlated with HDL-C (β = 0.220, p = 0.005).
In PAD patients, sCD146 was negatively correlated with HDL-C (β = −0.156, p = 0.041).
The interaction between group (PAD vs. control) and HDL-C on sCD146 was statistically significant (p = 0.002).
This sign reversal suggests metabolic dysregulation specifically in PAD patients affecting the normal sCD146-HDL-C relationship.
Results
The age-adjusted odds ratio for PAD associated with lower sCD146 was highest among individuals in the high HDL-C tertile.
Age-adjusted OR for PAD was 1.41 (95% CI: 1.22–1.63) in individuals with high HDL-C tertiles.
This finding highlights that the combination of low sCD146 and high HDL-C may be particularly informative for PAD risk.
The result is consistent with the observed negative sCD146-HDL-C correlation in PAD patients.
Methods
The study was a case-control design enrolling Caucasian men with symptomatic PAD and age-matched healthy controls.
184 PAD patients and 163 healthy controls were enrolled.
All participants were Caucasian men, limiting generalizability.
PAD was symptomatic and confirmed by ABI and vascular imaging.
The study was registered as NCT00377897.
What This Means
This research studied a protein called soluble CD146 (sCD146), which circulates in the blood and is released by the cells lining blood vessels. The scientists wanted to know whether blood levels of sCD146 could help identify peripheral artery disease (PAD), a condition where arteries in the legs become narrowed or blocked, reducing blood flow. They compared 184 men diagnosed with PAD to 163 healthy men of similar age, measuring sCD146 using a blood test. They found that men with PAD had dramatically lower sCD146 levels — about 40% lower — than healthy men, and this association held up even after accounting for known risk factors like smoking and diabetes. Importantly, sCD146 was not related to how severe the PAD was, suggesting it may signal the presence of the disease rather than how advanced it is.
One particularly notable finding was about the relationship between sCD146 and HDL cholesterol (often called 'good' cholesterol). In healthy men, higher HDL-C was linked to higher sCD146, which fits the expected picture of HDL protecting blood vessels. But in men with PAD, higher HDL-C was actually linked to lower sCD146 — the opposite pattern. This reversal suggests that in PAD, normal metabolic processes involving blood vessel health are disrupted in a fundamental way, and that HDL may not be functioning normally in this context.
This research suggests that measuring sCD146 in blood could potentially serve as a new diagnostic tool to help detect PAD, which is currently underdiagnosed. Since PAD is often missed until it causes serious complications, having additional blood-based markers could improve early detection. The unusual relationship between sCD146 and HDL cholesterol in PAD patients also points to deeper metabolic and vascular abnormalities in the disease that warrant further investigation.