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Diabetes-induced cardiovascular complications are mainly associated with high morbidity and mortality in patients with diabetes. Insulin-like growth factor II receptor α (IGF-IIRα) is a cardiac risk factor. In this study, we hypothesized IGF-IIRα could also deteriorate diabetic heart injury. The results presented that both in vivo transgenic Sprague-Dawley rat model with specific IGF-IIRα overexpression in the heart and in vitro myocardium H9c2 cells were used to investigate the negative function of IGF-IIRα in diabetic hearts. The results showed that IGF-IIRα overexpression aided hyperglycemia in creating more myocardial injury. Pro-inflammatory factors, such as Tumor necrosis factor-alpha, Interleukin-6, Cyclooxygenase-2, Inducible nitric oxide synthase, and Nuclear factor-kappaB inflammatory cascade, are enhanced in the diabetic myocardium with cardiac-specific IGF-IIRα overexpression. Correspondingly, IGF-IIRα overexpression in the diabetic myocardium also reduced the PI3K-AKT survival axis and activated mitochondrial-dependent apoptosis. Finally, both ejection fraction and fractional shortening were be significantly decrease in diabetic rats with cardiac-specific IGF-IIRα overexpression. Overall, all results provid clear evidence that IGF-IIRα can enhance cardiac damage and is a harmful factor to the heart under high-blood glucose conditions. However, the pathophysiology of IGF-IIRα under different stresses and its downstream regulation in the heart still require further research.

Hypertension is a severe public health risk factor worldwide. Elevated angiotensin II (Ang II) produced by the renin-angiotensin-aldosterone system can lead to hypertension and its complications.In this study, we addressed the cardiac-injury effects of Ang II and investigated the signaling mechanism induced by Ang II. Both H9c2 cardiomyoblast cells and neonatal rat cardiomyocytes were exposed to Ang II to observe hypertension-related cardiac apoptosis.The results of western blotting revealed that Ang II significantly attenuated the IGF1R-PI3K-AKT pathway via the Ang II-AT1 receptor axis and phosphatase and tensin homolog expression. Furthermore, real-time PCR showed that Ang II also activated miR-320-3p transcription to repress the PI3K-Akt pathway. In the heart tissue of spontaneously hypertensive rats, activation of the IGF1R survival pathway was also reduced compared with that in Wistar-Kyoto rats, especially in aged spontaneously hypertensive rats.Hence, we speculate that the Ang II-AT1 receptor axis induces both phosphatase and tensin homolog and miR-320-3p expression to downregulate the IGF1R-PI3K-AKT survival pathway and cause cell apoptosis in the heart.

Heart failure (HF) and cardiac hypertrophy is an unfavorable outcome of pathological cardiac remodeling and represents the most important contributing factor for HF and cardiac hypertrophy. Amygdalin (AMG) is a cyanogenic glycoside derived from bitter almonds. Accumulating evidences have highlighted their pharmacological potentials against various diseases. However, there is no report delineating the potential of AMG against angiotensin (Ang II) induced cardiac injuries. Thus, the present study was performed to explore whether AMG could ameliorate Ang II induced cardiomyopathies and thereby ascertain the underlying mechanisms thereof. To this end, H9c2 cells were treated with Ang II and thereafter treated with various concentration of AMG and finally the cardio-protective effects of AMG were analyzed through Western blotting, immunofluorescence, and insilico analysis. Our results showed that the cardiomyocyte cell size, inflammatory markers and cytokines(pNF-κB, TNF-α, iNOS and COX-2) were markedly increased following Ang II treatment; nevertheless, treatment with AMG led to considerable decrement in the Ang II induced enlargement of the cardiomyocytes, and attenuate the expression of hypertrophic markers(ANP, BNP and MHC-7), inflammatory markers and cytokines. Additionally, oxidative stress related proteins (Nrf2, catalase, SOD-2, and GPX-4) were markedly increased following AMG treatment. Molecular docking reveals the interaction of AMG with Nrf2 possessing good binding affinity. Cumulatively, our study highlights the cardio-protective role of AMG against Ang II induced cardiomyopathies, including oxidative stress and inflammation effects. The intriguing in vitro results warrants the need of further animal studies to truly ascertain their potentialities.

Background: Percutaneous coronary intervention (PCI) to chronic total occlusion (CTO) has become one of the treatment strategies in recent era. The ostium of the left anterior descending artery (LAD) is one of the most difficult positions for CTO revascularization. Until now, limited data has been made available for the prediction of successful ostial LAD CTO PCI. Objective: The aim of the study was to compare the differences between ostial LAD and all other CTOs and to identify the predictors of successful ostial LAD CTO PCI. Methods: This retrospective analysis included consecutive patients referred for CTO PCI between January 2001 and September 2013. Ostial LAD CTO was defined as CTO at the position whose distance between lesion and left main bifurcation was less than 1 mm. Baseline demographics, lesion characteristics, interventional procedure details, and devices were compared between the ostial LAD group and the all other CTOs group. The predictors of successful ostial LAD CTO PCI were also evaluated. Results: 621 patients who underwent CTO PCI were enrolled retrospectively to this study. A total of 70 patients of ostial LAD CTO were compared with 551 patients of all other CTOs group in this study. Ostial LAD CTO was found to have more bridging and better collaterals than all other CTOs. Procedure time, fluoroscopic time, contrast volumes, the use of contralateral injection, and the use of the retrograde approach were significantly greater in the ostial LAD CTO group. The ostial LAD CTO group also had significantly higher J-CTO scores (2.7 ± 0.8 vs. 2.2 ± 1.1, P = 0.011) and higher Syntax Scores (28.3 ± 6.5 vs. 20.9 ± 9.7, P

Percutaneous coronary intervention (PCI) to chronic total occlusion (CTO) has become one of the treatment strategies in recent era. The ostium of the left anterior descending artery (LAD) is one of the most difficult positions for CTO revascularization. Until now, limited data has been made available for the prediction of successful ostial LAD CTO PCI.The aim of the study was to compare the differences between ostial LAD and all other CTOs and to identify the predictors of successful ostial LAD CTO PCI.This retrospective analysis included consecutive patients referred for CTO PCI between January 2001 and September 2013. Ostial LAD CTO was defined as CTO at the position whose distance between lesion and left main bifurcation was less than 1 mm. Baseline demographics, lesion characteristics, interventional procedure details, and devices were compared between the ostial LAD group and the all other CTOs group. The predictors of successful ostial LAD CTO PCI were also evaluated.621 patients who underwent CTO PCI were enrolled retrospectively to this study. A total of 70 patients of ostial LAD CTO were compared with 551 patients of all other CTOs group in this study. Ostial LAD CTO was found to have more bridging and better collaterals than all other CTOs. Procedure time, fluoroscopic time, contrast volumes, the use of contralateral injection, and the use of the retrograde approach were significantly greater in the ostial LAD CTO group. The ostial LAD CTO group also had significantly higher J-CTO scores (2.7 ± 0.8 vs. 2.2 ± 1.1, P = 0.011) and higher Syntax Scores (28.3 ± 6.5 vs. 20.9 ± 9.7, P 0.001). A slightly lower final success rate, but statistically non-significant, was observed in the ostial LAD CTO group (80.0% vs. 81.9%, P = 0.706). Univariate and multivariate logistic regression revealed that without antegrade failure and with retrograde success were predictors of the success of ostial LAD CTO PCI. Syntax Score was also capable of predicting the ostial LAD CTO PCI outcome. J-CTO score was not found to be associated with final success for ostial LAD CTO patients.Ostial LAD CTO resulted in higher lesion complexity in J-CTO scores and Syntax Scores. Ostial LAD CTO PCI had a slightly lower final success rate than that of all other CTOs PCI with longer procedure duration, fluoroscopic time and larger contrast volume. Without antegrade failure, with retrograde success, and lower Syntax Score were found to predict the success of ostial LAD CTO PCI.