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Open Access Highly Accessed Original investigation

Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease

Surya Ramachandran1, Anila Venugopal1, V Raman Kutty2, Vinitha A1, Divya G1, V Chitrasree3, Ajit Mullassari3, N S Pratapchandran4, K R Santosh5, M Radhakrishna Pillai6 and C C Kartha1*

Author Affiliations

1 Cardiovascular Disease Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India

2 Achutha Menon Centre, SCTIMST, Thiruvananthapuram, India

3 Madras Medical Mission, Chennai, India

4 Indian Institute of Diabetes, Thiruvananthapuram, India

5 PRS Hospital, Thiruvananthapuram, India

6 Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India

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Cardiovascular Diabetology 2014, 13:38  doi:10.1186/1475-2840-13-38

Published: 7 February 2014

Abstract

Aims/hypothesis

Cyclophilin 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).

Methods

Study 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.

Results

Plasma 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/interpretations

Our 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.

Keywords:
Hyperglycemia; Type 2 diabetes mellitus; Monocytes; Cyclophilin A; Vascular disease