Association between Plasma Sestrin2 Levels and the Presence and Severity of Coronary Artery Disease

Abstract

Aims. Atherosclerotic disease, such as coronary artery disease (CAD), is recognized to be associated with inflammation and oxidative stress. We investigated the association between CAD and plasma levels of sestrin2 which is one of the stress-inducible antioxidant proteins. Methods. We measured plasma sestrin2 levels in 304 patients undergoing elective coronary angiography. The severity of CAD was represented as the numbers of >50% stenotic coronary vessels and segments and the severity score. Results. CAD was found in 175 patients, of whom 73 had 1-vessel (1-VD), 59 had 2-vessel (2-VD), and 43 had 3-vessel disease (3-VD). Plasma sestrin2 levels were significantly higher in 175 patients with CAD than in 129 without CAD (median 16.4 vs. 14.2 ng/mL, P<0.05). A stepwise increase in sestrin2 levels was found depending on the number of >50% stenotic coronary vessels: 14.2 in CAD(-), 15.4 in 1-VD, 17.3 in 2-VD, and 17.7 ng/mL in3-VD (P<0.05). High sestrin2 level (>16.0 ng/mL) was present in 38% of patients with CAD(-), 47% of 1-VD, 66% of 2-VD, and 53% of 3-VD (P<0.005). Sestrin2 levels significantly, but weakly, correlated with the number of >50% stenotic segments and the severity score (rs=0.12 and rs=0.13, P<0.05). In the multivariate analysis, sestrin2 levels were a significant factor associated with CAD independent of atherosclerotic risk factors. The odds ratio for CAD was 1.79 (95%CI=1.09‐2.95) for high sestrin2 level of >16.0 ng/mL (P<0.025). Conclusions. Plasma sestrin2 levels in patients with CAD were found to be high and to be associated with the severity of CAD. High sestrin2 levels in patients with CAD may reflect a protective response against the progression of CAD.

The Protective Role of Sestrin2 in Atherosclerotic and Cardiac Diseases

“…The odds ratio for severe plaque was 5.70 (95%CI: 1.99–16.35) for a high sestrin2 level (>13.0 ng/mL). These findings demonstrated that the plasma sestrin2 levels were high in individuals with carotid plaques and were associated with the severity of carotid atherosclerosis, as reported in patients with CAD [ 39 ]. High plasma sestrin2 levels may reflect an increased oxidative stress condition and may function to help protect the body against the progression of atherosclerosis.…”

“…Sestrin2 is suggested to be associated with aging and age-related diseases [ 12 , 36 ], and blood sestrin2 levels were reported to correlate with age [ 37 , 38 ]. Kishimoto et al also reported that plasma sestrin2 levels correlated with age (r = 0.29) in 304 patients undergoing coronary angiography [ 39 ]. Moreover, sestrin2 was demonstrated to be associated with an aging-related process, and physical exercise can upregulate sestrin2 [ 40 ].…”

“…Kishimoto et al recently investigated plasma sestrin2 levels in 304 patients undergoing coronary angiography for suspected CAD [ 39 ]. Patients with acute coronary syndrome, defined as acute MI and UA, were excluded from the study, and since plasma sestrin2 levels in patients with heart failure were reported to be high [ 6 ], patients with heart failure were also excluded.…”

“…Thus, high plasma sestrin2 levels were identified in the patients with CAD. However, because sestrin2 is secreted by various types of cells including macrophages, T lymphocytes, endothelial cells, and cardiomyocytes [ 6 , 9 , 10 ] and because sestrin2 levels were not measured in the coronary sinus in the Kishimoto et al study [ 39 ], the main sources of sestrin2 in patients with CAD remain unclear. Moreover, as shown in Figure 2 , there was a substantial overlap in sestrin2 levels between the patients with and without CAD.…”

“…The central lines represent the median, and the boxes represent the 25th to 75th percentiles. The whiskers represent the lowest and highest values in the 25th percentile minus 1.5 interquartile range (IQR) and the 75th percentile plus 1.5 IQR, respectively (modified from Kishimoto et al [ 39 ]).…”