RESUMEN
UNLABELLED: Cardiomyocytes apoptosis is an important contributor to myocardial dysfunction and heart failure. Adiponectin has cardioprotective effects, potential mechanisms behind it are not clear in cardiomyocytes. The purpose of the study was to investigate whether adiponectin can block palmitate-induced apoptosis and the underlying biochemical mechanism in H9c2 cells. METHODS: H9c2 cells were treated with palmitate presence or absence of 2.5 µg/mL globular adiponectin. The effect on the cell viability of H9c2 cells was evaluated using MTT assay, and cell apoptosis was determined by Hoechst 33342 staining. Protein expression was measured using the western blot method. RESULTS: Our results showed that the palmitate treatment induced apoptosis in H9c2 cells, which was associated with increasing the level of cleaved caspase-3 and cleaved PARP. Meanwhile, palmitate-induced apoptosis increased the protein level of p-ERK1/2, and decreased the protein level of p-Akt significantly. However, levels of both of these proteins were restored to the normal when pretreated with adiponectin, and followed with the decrease of cleaved caspase-3 and cleaved PARP. In line with these results, the protective effect of adiponectin can be blocked by PI3K/Akt inhibitor LY294002, and palmitate-induced apoptosis can be attenuated by ERK1/2 inhibitor U0126. CONCLUSIONS: Taken together, the present study demonstrated that adiponectin protects H9c2 cells from palmitate-induced apoptosis via PI3K/Akt and ERK1/2 signaling pathways. Our results reveal a link between adiponectin and cardiomyocytes apoptosis, suggesting that adioponectin may be a promising therapeutic for the treatment of lipotoxicity cardiomyopathy.
Asunto(s)
Adiponectina , Cardiotónicos/farmacología , Miocitos Cardíacos , Proteína Oncogénica v-akt/metabolismo , Adiponectina/metabolismo , Adiponectina/farmacología , Animales , Apoptosis/efectos de los fármacos , Cromonas/farmacología , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Morfolinas/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Palmitatos/toxicidad , Ratas , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: Testosterone is either neutral or has a harmful effect on the male cardiovascular system. But the role of imbalance of testosterone (T) and estrogen (E2) (T/E2 ratio) in male CHD has been less studied. This study was carried out with the purpose of evaluating the relationship between T/E2 ratio and CHD. METHODS: Fifty-five male CHD patients (aged 61.25 ± 3.44) and 60 age-matched controls (aged 59.54 ± 1.44) were selected in this research. RESULTS: Compared with control group, levels of both serum T and E2 decreased, but only E2 had statistical significance (P=0.001). The normal testosterone (T)/estradiol (E2) ratio is 1.7 ± 0.12, but the ratio of T/E2 (3.28 ± 0.58) changed significantly in men with CHD group (P<0.05). With the imbalance of T/E2 ratio in CHD group, we further used a linear and multiple regression methods to analyze the correlation between sex hormones and CHD risk factors. The results showed serum T was positively associated with TG (r=0.439, P<0.01) and D-dimer (r=0.258, P<0.05), but negatively associated with HDL-C (r=-0.267, P<0.05) and Hs-CRP (r=-0.214, P<0.05). However, E2 was highly positive associated with TG (r=0.783, P<0.01) and HDL-C (r=0.515, P<0.01), but was negative related with LDL-C (r=-0.219, P<0.05), TC/LDL (r=-0.236, P<0.05) and D-dimer. Multiple linear regression method also showed the same results between E2 and HDL-C (P=0.020), LDL-C (P=0.000), which showed E2's protective role in cases. However, T/E2's effect is more significative than E2's, and the values between T/E2 and index are HDL-C (r=-0.624, P<0.01), LDL-C (r=0.348, P<0.01), TC/HDL (r=0.237, P<0.05), Hs-CRP (r=0.248, P<0.05) and D-dimer (r=0.249, P<0.05). Multiple linear regression method also showed the positive relationship between T/E2 and HDL-C (P=0.000), D-dimer (P=0.000), and negative relationships between T/E2 and TC (P=0.000), TG (P=0.000) or HDL/LDL (P=0.000). CONCLUSION: The balance of T/E2 ratio, rather than the absolute levels of androgens, is crucial in modulating the effect of androgens on CHD in males.