Serum adropin level in patients with stable coronary artery disease.

OBJECTIVES: Adropin is a newly identified secreted protein implicated in the regulation of insulin sensitivity and vascular endothelial function. Recent studies have shown that lower serum adropin level is related to acute myocardial infarction and coronary atherosclerosis. The primary objective of this study was to ascertain the association of serum adropin level with stable coronary artery disease (SCAD). METHODS: We prospectively recruited a cohort of patients with SCAD and similar sample size subjects without coronary artery disease as controls. Their serum adropin levels were measured, and the severity of coronary atherosclerosis in SCAD patients was quantified with the syntax score. RESULTS: A total of 116 patients with SCAD and 116 control subjects without coronary artery disease were recruited. Patients with SCAD had lower serum adropin levels when compared with the controls (59.2±19.3 versus 70.0±18.2 pg/mL, P<0.001). The multiple logistic regression revealed that low serum adropin level was a significant predictor of SCAD (AOR 0.976, 95% CI 0.960-0.992; p=0.003). Through the gamma regression model, it was further revealed that serum adropin level is significantly associated with syntax score (coefficient: -0.134, 95% CI: -0.212- -0.056; p=0.001). CONCLUSIONS: Low serum adropin level is a significant predictor of SCAD. It is also associated with syntax score, thus indicating the close relationship between adropin and coronary atherosclerosis.

Adropin inhibits the phenotypic modulation and proliferation of vascular smooth muscle cells during neointimal hyperplasia by activating the AMPK/ACC signaling pathway.

In-stent restenosis (ISR) remains an inevitable problem for some patients receiving drug-eluting stent (DES) implantation. Intimal hyperplasia is an important biological cause of ISR. It has been previously reported that adropin is a potentially protective factor in cardiovascular disease. Therefore, the present study investigated the function of adropin in inhibiting smooth muscle cell (SMC) phenotype modulation and proliferation, causing intimal hyperplasia. A total of 56 patients who visited the hospital consecutively (25 with ISR and 31 without ISR), who were followed up between April 2016 and March 2019, 1 year following DES, were analyzed to evaluate the association between in-stent neointimal volume and adropin serum levels. Rat aorta smooth muscle cells (RASMCs) were used to determine the effects of adropin on their phenotypic modulation and proliferation using western blot, MTT, PCR and immunofluorescence analyses. Adropin serum levels in the ISR group were significantly lower than those in the non-ISR group. Furthermore, linear regression analysis revealed that only adropin levels were negatively associated with neointimal volume in both groups. The overall adropin levels of the 56 patients and the percentages of neointimal volume revealed a strong negative association. In vitro, adropin suppressed angiotensin II (Ang II)-induced phenotypic modulation in RASMCs by restoring variations of osteopontin and α-smooth muscle actin. Furthermore, compared with the Ang II group, adropin markedly decreased the percentage of G2/M-phase cells. Finally, adropin negatively regulated the phenotypic modulation and proliferation of RASMCs via the AMP-activated protein kinase/acetyl-CoA carboxylase (AMPK/ACC) signaling pathway. In conclusion, an independent, negative association was revealed between adropin and intimal hyperplasia; specifically, adropin inhibited the phenotypic modulation and proliferation of RASMCs by activating the AMPK/ACC signaling pathway. Therefore, adropin may be used as a potential predictor and therapeutic target for intimal hyperplasia and ISR.

Adropin is associated with hyperhomocysteine and coronary atherosclerosis.

Homocysteine has been recognized as a risk factor for atherosclerosis and cardiovascular diseases. Adropin is a newly-identified energy homeostasis protein with a potential protective effect against coronary artery disease (CAD). This study attempted to measure the correlation between serum homocysteine and adropin levels in patients with CAD, and to ascertain how the two hormones could affect the severity of coronary atherosclerosis. A cohort of CAD patients who had undergone coronary angiography was prospectively recruited. The serum homocysteine and adropin levels of the patients were measured and the severity of coronary atherosclerosis was quantified with the SYNTAX score. The data were analyzed with a generalized structural equation model. In total, 170 consecutive patients were recruited with a mean serum homocysteine level of 15.9±8.3 µmol/l, and 76 (44.7%) patients were identified as hyperhomocysteinemic with a serum homocysteine level >15 µmol/l. Serum homocysteine level was found to be significantly negatively correlated with serum adropin level (r=-0.169, P=0.028). Patients with hyperhomocysteinemia had lower serum adropin levels and higher SYNTAX scores than patients without hyperhomocysteinemia. Further analysis with a generalized structural equation model showed that adropin was significantly associated with hyperhomocysteinemia (adjusted odds ratio: 0.95, 95% confidence interval: 0.93 to 0.98; P=0.002), which in turn was significantly associated with the SYNTAX score (coefficient: 4.71, 95% confidence interval: 1.39 to 8.03; P=0.005). In conclusion, the serum homocysteine level was inversely correlated with the serum adropin level in patients with CAD. A low serum adropin level was associated with hyperhomocysteinemia and more severe coronary atherosclerosis, as reflected by a higher SYNTAX score.

Influence of insulin resistance on in-stent restenosis in patients undergoing coronary drug-eluting stent implantation after long-term angiographic follow-up.

OBJECTIVE: Previous studies have reported that insulin resistance is related to early in-stent restenosis (ISR) after coronary stenting. This study aimed to evaluate the influence of insulin resistance on the long-term angiographic outcome in patients undergoing coronary drug-eluting stent (DES) implantation. MATERIALS AND METHODS: Within a single hospital-based cohort of patients (n=529) who underwent coronary DES implantation, angiographic follow-up was performed successfully for 417 study patients at 12-48 months after coronary stenting. ISR was defined as stenosis of at least 50% of the luminal diameter. Fasting plasma glucose and fasting plasma insulin were measured. Insulin resistance was expressed by the homeostasis model assessment index (HOMA-IRI). RESULTS: Among the 417 patients who completed angiographic follow-up (mean 17.5±10.2 months), 58 patients (13.9%) had ISR whereas the remaining 359 patients (86.1%) did not have ISR. Patients with ISR had higher insulin resistance index (IRI) than nonrestenosis patients (P=0.004). Multiple logistic regression analysis (logit) showed that IRI was associated significantly with ISR (adjusted odds ratio 1.476, 95% confidence interval 1.227-1.776; P<0.001). In the nondiabetes subgroup of 309 patients, IRI was higher in patients with ISR than in nonrestenosis patients, as confirmed in a separate logit analysis (adjusted odds ratio 1.456, 95% confidence interval 1.152-1.839; P=0.002). Multiple linear regression analysis showed that IRI was associated significantly with in-stent diameter stenosis degree (P=0.043). CONCLUSION: Insulin resistance was associated with ISR in patients undergoing coronary DES implantation at long-term angiographic follow-up.