Abstract
Aims/hypothesisCyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD).MethodsStudy subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored.ResultsPlasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P < 0.001). Age, fasting blood sugar levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p < 0.001).Serum levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease.Conclusions/interpretationsOur study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease suggesting a role of this protein in accelerating vascular disease in type 2 diabetes. Considering the evidence that Cyclophilin A is an inflammatory mediator in atherogenesis, the mechanistic role of cyclophilin A in diabetic vascular disease progression deserves detailed investigation.
Highlights
Cyclophilin A is part of various intracellular functions, such as intracellular signaling, protein trafficking, and regulating activity of other proteins [1]
Baseline clinical parameters of patients with diabetes, coronary artery disease and controls A total of 313 diabetes patients; 212 with CAD and 101 without CAD (210 men and 103 women), 122 patients with only coronary artery disease (102 men and 20 women) and 121 normal healthy volunteers (66 men and 55 women) without any evidence of systemic disease participated in the study
Mean Glycated haemoglobin (HbA1c) values were highest in the diabetes mellitus (DM) group followed by the group of patients with diabetes and coronary artery disease (DM + CAD10y)
Summary
Cyclophilin A is part of various intracellular functions, such as intracellular signaling, protein trafficking, and regulating activity of other proteins [1]. Cyclophilin A, is well recognized as a secreted growth factor that is induced by oxidative stress [2] functioning as a mediator of tissue damage associated with inflammation and oxidative stress [3]. The secretory nature of this protein and its presence in plasma of patients with DM and CAD underlines its potential as a marker of disease. We demonstrated secretion of cyclophilin A from monocytes under hyperglycemic conditions. Preliminary studies on a small number of patients with type 2 diabetes mellitus and coronary artery disease revealed increased plasma levels of cyclophilin A compared to normal healthy individuals [4]
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