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September 12, 2026Journal of the American College of Cardiology353 citationsOpen Access

Elevated Levels of VE-Cadherin-Positive Endothelial Microparticles in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

HKHidenobu KogaSSSeigo SugiyamaKKKiyotaka Kugiyama

Key Result

In patients with type 2 diabetes, elevated levels of CD144-EMP were significantly associated with coronary artery disease (OR 3.5; 95% CI 1.8 to 6.9; p < 0.001).

Key Points

  • To determine whether CD144-positive endothelial microparticles act as a specific quantitative biomarker of endothelial cell dysfunction and predict coronary artery disease in patients with type 2 diabetes.
  • Characterized CD144-positive microparticles across atherosclerosis-related cells and assessed their correlation with in vitro hydrogen-peroxide-induced injury and in vivo acetylcholine-induced coronary vasomotion.
  • Measured and compared plasma CD144-positive endothelial microparticle levels in patients with and without type 2 diabetes mellitus to evaluate coronary artery disease risk.
  • CD144-positive microparticle levels correlated with impaired endothelium-dependent coronary vasodilation (p < 0.01) and were significantly elevated in patients with diabetes compared to those without (p < 0.01).
  • Elevated CD144-positive microparticles were the strongest independent predictor for coronary artery disease in diabetic patients (odds ratio [OR] 3.5, 95% CI 1.8 to 6.9, p < 0.001) and effectively detected disease in asymptomatic diabetic individuals (OR 10.6, 95% CI 3.9 to 29.5, p < 0.001).

Study Design

Type

Observational

PICO

P
Population
Patients with and without type 2 diabetes mellitus evaluated for the association between plasma CD144-EMP levels and coronary artery disease.
E
Exposure / Comparator
Elevated plasma CD144-EMP levels vs Lower plasma CD144-EMP levels
O
Primary Outcome
Coronary artery disease — OR 3.5 (1.8 to 6.9), p=<0.001

Main Result

Odds Ratio: 3.5 (95% CI 1.8–6.9)

p-value: p=<0.001

Abstract

OBJECTIVES: The purpose of this study was to examine whether CD144-EMP (endothelium-derived microparticles) is useful as a specific marker of endothelial cell (EC) dysfunction and to determine whether plasma levels of circulating CD144-EMP predicted coronary artery disease (CAD) in patients with type 2 diabetes mellitus (DM). BACKGROUND: Endothelial cell dysfunction is involved in atherogenesis; however, the quantitative assessment of EC dysfunction has yet to be established clinically. Endothelium-derived microparticles are small, membrane-shed vesicles that are generated from the EC surface in response to cellular dysfunction and/or injury. Diabetes mellitus is known to be associated with EC dysfunction and accelerated atherosclerosis. METHODS: We characterized EMP using anti-CD144 (VE-Cadherin) antibody in various atherosclerosis-related cells and investigated the association between the levels of CD144-positive microparticles and hydrogen-peroxide-induced EC injury and acetylcholine-induced coronary vasomotion. Furthermore, we evaluated plasma CD144-EMP levels in patients with and without DM. RESULTS: We demonstrated that CD144-positive microparticles were derived selectively from human EC. The levels of CD144-EMP reflected the degree of in vitro hydrogen-peroxide-induced EC injury and impairment of in vivo endothelium-dependent coronary vasodilation (p < 0.01). Plasma CD144-EMP levels were increased significantly in DM patients compared with patients without DM (p < 0.001). In DM patients, the elevated levels of CD144-EMP were the most significant risk factor for CAD relative to all other traditional risk factors (odds ratio OR 3.5, 95% confidence interval CI 1.8 to 6.9, p < 0.001). Notably, plasma CD144-EMP identified a subpopulation of established CAD patients in DM subjects without typical anginal symptoms (OR 10.6, 95% CI 3.9 to 29.5, p < 0.001). CONCLUSIONS: The CD144-positive EMP exist in human plasma, and plasma CD144-EMP levels can be a clinically specific and quantitative marker of EC dysfunction and/or injury. Measurement of CD144-EMP, by providing a quantitative assessment of EC dysfunction, may be useful for identifying DM patients with increased risk of CAD.

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Cite This Study

Koga et al. (2005) conducted an observational in Type 2 diabetes mellitus and coronary artery disease. Elevated plasma CD144-EMP levels vs. Lower plasma CD144-EMP levels was evaluated on Coronary artery disease (OR 3.5, 95% CI 1.8 to 6.9, p=<0.001). In patients with type 2 diabetes, elevated levels of CD144-EMP were significantly associated with coronary artery disease (OR 3.5; 95% CI 1.8 to 6.9; p < 0.001).

synapsesocial.com/papers/6aa4c499f77744a392ce6027https://doi.org/10.1016/j.jacc.2005.02.047
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