Role of copper and its complexes in cardiovascular diseases / 中南大学学报(医学版)

Copper is a trace element essential for the maintenance of normal physiological functions in cardiovascular system,and its transport and metabolisms are regulated by various copper proteins such as copper-based enzymes,copper chaperones and copper transporters.The disturbance of copper level or abnormal expression of copper proteins are closely associated with the development of cardiovascular diseases such as atherosclerosis,hypertension,ischemic heart disease,myocardial hypertrophy and heart failure.Thus,intervention of copper ion signaling pathways is expected to be an effective measure for treating cardiovascular diseases.Some copper complexes,such as trientine,copper-aspirinate complex and copper(Ⅱ)diethyldithiocarbamate,have been found to play a role in the prevention and treatment of cardiovascular diseases and possess potential prospects.Exploring the role of copper in maintaining normal cardiovascular status and the potential application of copper complexes in the treatment of cardiovascular diseases may lay a foundation for finding new targets for prevention and treatment of various cardiovascular diseases,and provide new ideas for clinical treatment of cardiovascular diseases.

Role of ACE2-Ang (1-7)-Mas receptor axis in heart failure with preserved ejection fraction with hypertension / 中南大学学报(医学版)

To investigate changes in the angiotensin converting enzyme 2 (ACE2) and angiotensin (1-7) [Ang (1-7)] and to explore the role of ACE2-Ang (1-7)-Mas receptor axis in hypertension with heart failure with preserved ejection fraction (HFPEF).
 Methods: A total of 70 patients with primary hypertension and preserved left ventricular ejection fraction (LVEF>50%) were recruited and patients were divided into a hypertension group (HBP) and a heart failure with preserved ejection fraction group (HFpEF) according to the diagnostic criteria of HFpEF. Thirty-five healthy participants were selected randomly as a control group. Enzyme linked immunosorbent assays (ELISA) method was used to detect concentration of Ang (1-7), ACE2, angiotensin II (Ang II), brain natriuretic peptide (BNP) in plasma. Male Sprague- Dawley (SD) rats was randomly divided into 2 groups: An HFpEF group (n=16) and a sham group (n=8). Rats (n=8) in the AAC group were given Ang (1-7) [0.5 mg/(kg.d), intraperitoneally] for 6 weeks, and the rest were given equal dose normal saline. Then all the rats were killed, and the hearts were taken out for hematoxylineosin (HE) staining. The protein expressions of angiotensin converting enzyme (ACE), ACE2, and Mas receptor were detected by Western blot.
 Results: The BNP and Ang II were significantly increased in the HBP group and the HFpEF group compared with the control group (P0.05), whereas those levels were significantly increased in the HFpEF group compared with the HBP group and control group (P0.05).
 Conclusion: ACE2 and Ang (1-7) are important predictive factors for the severity of heart failure and myocardial remodeling of HFpEF with hypertension; ACE2-Ang (1-7)-Mas receptor axis may play a protective role in preventing myocardial remodeling in HFpEF with hypertension.

Association between interleukin-18 and Global Registry of Acute Coronary Events score in patients with acute coronary syndrome / 中南大学学报(医学版)

OBJECTIVE@#To determine the correlation between interleukin-18 (IL-18) level and Global Registry of Acute Coronary Events (GRACE) risk score as well as risk stratification in patients with acute coronary syndrome (ACS), and to determine the clinical prognostic value of IL-18 for major adverse cardiac events (MACE) in ACS patients.@*METHODS@#A total of 150 ACS patients were subjected to risk assessment and stratification with GRACE risk score. All ACS patients received conventional treatments and MACE was recorded. Plasma IL-18 was measured by enzyme-linked immunosorbent assay and the relationship between plasma IL-18 level and GRACE scores in ACS patients was analyzed. Predictive accuracy of IL-18 level and GRACE risk score for MACE were determined by receiver operating characteristic curve and the corresponding area under the curve.@*RESULTS@#According to GRACE risk stratification, IL-18 level was significantly elevated in the high risk group (>140) compared with that in the middle risk group (109-140; P<0. 05), while IL-18 level was significantly elevated in the middle risk group compared with that in the low risk group (≤108; P<0. 05). According to the IL-18 level, patients were stratified into 4 groups by quartile (from the lowest to the highest, Q1-Q4). Compared with Q1-Q3 groups, the GRACE risk score and percentage of high risk patients were the highest in the Q4 group (P<0.05). Receiver operating characteristic curve analysis showed that IL-18 level was positively related with GRACE risk score and that the area under the curve of IL-18 level and GRACE risk score for predicting MACE in hospital patients were 0.887 and 0.914, respectively.@*CONCLUSION@#Both IL-18 level and GRACE risk score are valuable parameters for risk of MACE in patients with ACS. IL-18 may be an important biomarker in the prognosis of ACS patients.

Protective effect of insulin-like growth factor-1 on vascular endothelial function in hypercholesterolemia and the underlying mechanism / 中南大学学报(医学版)

OBJECTIVE@#To investigate the relationship between insulin-like growth factor-1 (IGF-1) in the serum and the vascular endothelial function in patients with hypercholesterolemia and the underlying mechanism.@*METHODS@#We examined the flow-mediated arterial diastolic function (FMD), the levels of IGF-1, asymmetric dimethylarginine (ADMA), NO, and the activity of nitric oxide synthase (NOS) in the serum from 25 patients with hypercholesterolemia and from healthy controls. An endothelial cell injury model was established by incubation of the human umbical vein endothelial cells (HUVECs) with oxidized low-density lipoprotein (ox-LDL) for 24 hours. Cells were treated with IGF-1 30 min before ox-LDL treatment. The levels of ADMA, NOS, and NO in the cell supernatant, the activity of dimethylarginine dimethylamine hydrolase (DDAH) in the cell lysate were measured. Beta-galactosidase staining was used to assess the degree of endothelial cell senescence by calculating the senescence rate of cells.@*RESULTS@#Compared with the control group, the FMD, the levels of IGF-1 and NO, and the activity of NOS in the serum from patients with hypercholesterolemia decreased significantly accompanied with a dramatic increase at ADMA level. Multiple linear regression analysis showed that the change in IGF-1 was positively correlated with FMD while the change in ADMA was negatively correlated with FMD. Compared with the control group, ox-LDL treatments significantly decreased the activities of DDAH and NOS, and the level of NO, accompanied with an increase in ADMA. Betagalactosidase staining showed that the senescence rate of cells increased in the ox-LDL group. The effect of ox-LDL on HUVECs was significantly attenuated at the presence of IGF-1.@*CONCLUSION@#The decrease in IGF-1 in the peripheral blood may contribute to vascular endothelial dysfunction in patients with hypercholesterolemia. IGF-1 can protect HUVECs against ox-LDL-induced senescence, which is likely involved in the regulation of DDAH/ADMA pathway.