Deficiency of a New Protein Associated with Cardiac Syndrome X; Called Adropin

Abstract

SUMMARYThe pathophysiology of cardiac syndrome X (CSX) is still unclear, but most patients with CSX have endothelial dysfunction. It has been shown that adropin uniquely effects the regulation of endothelial function. The purpose of the study was to evaluate the role of adropin in CSX. Eighty-six consecutive cardiac syndrome X-diagnosed patients and 86 age-sex matched healthy subjects were enrolled into the study. Serum adropin levels, nitrite/nitrate levels were measured in each subject. The adropin levels were significantly lower in patients with CSX than healthy subjects (1.7 AE 0.8 ng/mL and 3.4 AE 1.8 ng/mL, respectively; P < 0.001). The BMI values of patients with CSX were significantly higher than control subjects (28.1 AE 2.4 kg/m 2 and 26.0 AE 3.7 kg/m 2 , respectively; P < 0.001). Plasma nitrite/ nitrate levels were lower in patients with CSX than control subjects (15.9 AE 1.6 lmol/L vs. 25.4 AE 2.8 lmol/L, respectively; P < 0.001), and they have a significantly positive correlation with plasma adropin levels (r = 0.463, P < 0.001). In the multiple linear regression analysis, nitrite/nitrate levels, BMI, and adropin were found to be independent risk factors for CSX. A ROC curve is used to identify the ability of adropin levels to predict the cardiac syndrome X. The area under the ROC curve was 0.854 for adropin levels (P = 0.0001). The sensitivity and specificity values of adropin levels were 90.7 and 70.9%, respectively (cutoff value 2.73). In conclusion, lower serum adropin levels were associated with CSX. Adropin is an independent risk factor for CSX.Patients with a normal coronary angiogram, effort-induced angina pectoris, positive exercise stress test, and/or positive single-photon emission computed tomography study are considered to have cardiac syndrome X (CSX) [1]. The long-term prognosis of patients with CSX appears to be good, but these patients have recurrent chest pain attacks, a situation that does increase the rate of morbidity. The pathogenesis of CSX is still unclear. Although endothelial dysfunction is regarded as one of the main underlying reasons for CSX, the pathophysiology seems to be more complex. Motz et al. [2] first showed the impaired coronary endothelial function in patients with CSX. Patients with CSX have increased resistance in coronary flow which is attributed to endothelial dysfunction in microcirculation [3]. The endothelium has very important roles in the control of vascular tone, including regulation of both vasodilatory substances such as nitric oxide and prostacycline, and vasoconstrictive substances such as endothelin-1 and angiotensin II [4]. An adequate balance between these vasoconstrictors and vasodilators is essential for maintaining vascular homeostasis. Nitric oxide synthesized from the amino acid L-Arginine by the endothelial nitric oxide-synthetase (eNOS) enzyme plays a key role in the regulation of vascular tone and also inhibits the activation of plaque and leukocytes and has an antiproliferative effect on smooth vascular muscle [4]. L-arginine and tetra...

Aerobic exercise training-induced changes in serum adropin level are associated with reduced arterial stiffness in middle-aged and older adults

“…In fact, we observed that the circulating adropin concentration in the healthy middle-aged and older adults was 2.43 Ϯ 0.92 ng/ml before aerobic exercise-training intervention, whereas after exercise training, the circulating adropin concentration was 4.37 Ϯ 1.30 ng/ml. By contrast, in patients with endothelial dysfunction and/or developing arterial stiffness risks, the circulating adropin concentration was 1.7 Ϯ 0.8 ng/ml (8). Although the risk of cardiovascular disease increases with age, this study exclusively recruited healthy middle-aged and older subjects.…”

“…Recent clinical studies reported a fall in circulating adropin level in patients with cardiovascular diseases, such as coronary artery disease, cardiac syndrome X, and stable angina pectoris, relative to healthy control adults (8,33,34). Furthermore, in patients with type 2 diabetes mellitus (30) and children with obstructive sleep apnea (13), low circulating adropin levels are associated with endothelial dysfunction, as assessed by using brachial flow-mediated dilatation (FMD) and forearm reactive hyperemia after cuff-induced occlusion.…”

“…Thus adropin may participate in the mechanism underlying the reduction in arterial stiffness mediated by NO-derived vasodilation in response to aerobic exercise training in middle-aged and older adults. Moreover, circulating adropin level is positively correlated with plasma NOx level in patients with cardiovascular disease (8). However, the association between aerobic exercise training-induced changes in arterial stiffness and circulating adropin level in healthy middle-aged and older adults remains unclear.…”

Adropin Is a Brain Membrane-bound Protein Regulating Physical Activity via the NB-3/Notch Signaling Pathway in Mice

“…Correlations between circulating adropin levels and different pathophysiological states in mice and humans have been reported (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In brief, the circulating concentration of adropin was reduced markedly in several metabolic diseases, including obesity-associated insulin resistance (1,5,11); obesity-related, nonalcoholic fatty liver disease (11); gestational diabetes mellitus (7); and endothelial dysfunction (6,8,14). However, conversely, other studies found that plasma adropin levels in humans were not correlated inversely with obesity on the basis of body mass index (6,8,13) or with endothelial dysfunction (9).…”

“…In brief, the circulating concentration of adropin was reduced markedly in several metabolic diseases, including obesity-associated insulin resistance (1,5,11); obesity-related, nonalcoholic fatty liver disease (11); gestational diabetes mellitus (7); and endothelial dysfunction (6,8,14). However, conversely, other studies found that plasma adropin levels in humans were not correlated inversely with obesity on the basis of body mass index (6,8,13) or with endothelial dysfunction (9). In addition, unlike findings in mice, plasma adropin levels in humans do not change in response to fasting and refeeding (5).…”