Exosomes derived from cardiac parasympathetic ganglionic neurons inhibit apoptosis in hyperglycemic cardiomyoblasts.

Diabetic cardiomyopathy is known to involve two forms of cardiac cell death: apoptosis and necrosis. However, it remains unknown whether hyperglycemia-induced apoptosis in the H9c2 cell culture system is inhibited by parasympathetic ganglionic neurons (PGN) derived exosomes (exos). We isolated PGN and sympathetic ganglionic neurons (SGN) from the right stellate ganglion in rats, and derived exos from these sources. H9c2 cells were divided into 4 groups: (1) Control, (2) H9c2 + Glucose (100 mmol/L), (3) H9c2 + Glucose + PGN-exos, and (4) H9c2 + Glucose + SGN-exos. We determined cell proliferation and viability with an MTT assay kit, and assessed apoptotic cell death with TUNEL staining and ELISA. Data were further confirmed by analyzing the presence of pro-apoptotic proteins Caspase-3 and Bax, and anti-apoptotic protein Bcl-2. Glucose exposed H9c2 cells significantly reduced cell viability, which was improved by PGN-exos, but not by SGN-exos. Furthermore, increased apoptosis in hyperglycemia in H9c2 cells was confirmed with TUNEL staining and cell death ELISA which demonstrated significantly (p < 0.05) reduction with PGN-exos treatment, but not with SGN-exos. Moreover, high expression of pro-apoptotic proteins Caspase-3 and Bax was reduced following treatment with PGN-exos; however, SGN-exos were unable to reduce the expression. Significantly reduced anti-apoptotic protein Bcl-2 following glucose treatment was improved with PGN-exos. Therefore, our data suggest that hyperglycemia induces apoptosis in H9c2 cells and decreases cell viability, and that PGN-exos are able to inhibit apoptosis, improve cell viability, and restore levels of anti-apoptotic protein Bcl-2.

Macrophage depletion by clodronate attenuates bone morphogenetic protein-7 induced M2 macrophage differentiation and improved systolic blood velocity in atherosclerosis.

Bone morphogenetic protein-7 (BMP-7) affects the presence of macrophage subtypes in vitro and in vivo at an early stage of atherosclerosis (ATH); however, it remains unknown whether BMP-7 treatment affects the development and progression of ATH at a mid-stage of the disease. We therefore performed a Day 28 (D28) study to examine BMP-7's potential to affect monocyte differentiation. Atherosclerosis was developed in ApoE KO mice, and these animals were treated with intravenous injections of BMP-7 and/or liposomal clodronate (LC). BMP-7 significantly (P < 0.05) lowers plaque formation following induction of atherosclerosis. However, upon macrophage depletion, BMP-7 fails to significantly alter plaque progression suggesting a direct role of BMP-7 on macrophages. Immunohistochemical staining of carotid arteries was performed to determine BMP-7's effect on pro-inflammatory M1 inducible nitric oxide synthase and anti-inflammatory M2 (cluster of differentiation [CD]206, Arginase-1) macrophages, and monocytes ( CD14). BMP-7 significantly reduced pro-inflammatory M1 macrophages and increased anti-inflammatory M2 macrophages at D28, while BMP-7 showed no effect on M2 macrophage differentiation in animals treated with LC. Enzyme-linked immunosorbent assay data showed significant reduction in proinflammatory cytokines (Interleukin-6 [IL-6]), monocyte chemoattractant protein-1, and tumor necrosis factor-α) and a significant increase in anti-inflammatory cytokine (IL-10) in BMP-7 treated mice (P < 0.05).Western blot analysis of arterial tissue confirms a significant increase in pro-survival kinases extracellular-signal regulated kinase and SMAD and a reduction in pro-inflammatory kinases p38 and c-Jun N-terminal kinase in BMP-7 treated mice (P < 0.05). Overall, this study suggests that clodronate treatment inhibits BMP-7 induced differentiation of monocytes into M2 macrophages and improved systolic blood velocity.

3D modeling: a future of cardiovascular medicine 1.

Cardiovascular disease resulting from atypical cardiac structures continues to be a leading health concern despite advancements in diagnostic imaging and surgical techniques. However, the ability to visualize spatial relationships using current technologies remains a challenge. Therefore, 3D modeling has gained significant interest to understand complex and atypical cardiovascular disorders. Moreover, 3D modeling can be personalized and patient-specific. 3D models have been demonstrated to aid surgical planning and simulation, enhance communication among surgeons and patients, optimize medical device design, and can be used as a potential teaching tool in medical schools. In this review, we discuss the key components needed to generate cardiac 3D models. We highlight prevalent structural conditions that have utilized 3D modeling in pre-operative planning. Furthermore, we discuss the current limitations of routine use of 3D models in the clinic as well as future directions for utilization of this technology in the cardiovascular field.