Shock Wave Therapy Promotes Cardiomyocyte Autophagy and Survival during Hypoxia

Abstract

Background: Autophagy plays an important role in cardiovascular disease. Controversy still exists regarding the effect of autophagy on ischemic/hypoxic myocardium. Cardiac shock wave therapy (CSWT) is an effective alternative treatment for refractory ischemic heart disease. Whether CSWT can regulate cardiomyocyte autophagy under hypoxic conditions is not clear. We established a myocardial hypoxia model using the H9c2 cell line and performed shock waves (SWs) treatment to evaluate the effect of SW on autophagy. Methods: The H9c2 cells were incubated under hypoxic conditions, and SW treatment was then performed at energies of 0.02, 0.05, or 0.10 mJ/mm². The cell viability and intracellular ATP level were examined. Western blot analysis was used to assess the expression of LC3B, AMPK, mTOR, Beclin-1, Sirt1, and HIF-1α. Autophagic vacuoles were visualized by monodansylcadaverine staining. Results: After the 24-hour hypoxic period, cardiomyocyte viability and ATP levels were decreased and autophagy was significantly increased in H9c2 cells. SW treatment with an energy of 0.05 mJ/mm² significantly increased the cellular viability, ATP level, LC3B-II/I, and number of autophagic vacuoles. In addition, phosphorylated AMPK and Sirt1 were increased and phosphorylated mTOR and HIF-1α were decreased after SW treatment. Conclusion: SW treatment can potentially promote cardiomyocyte autophagy during hypoxia and protect cardiomyocyte function by regulating the AMPK/mTOR pathway.

A predicted risk score based on the expression of 16 autophagy‑related genes for multiple myeloma survival

“…Among the five previously identified ARGs associated with MM, HIF1A is the most widely studied (59,60). Hypoxia, a central characteristic for cancer incidence and progression, occurs when most types of cancer are evolving (59)(60)(61)(62)(63)(64).…”

“…Among the five previously identified ARGs associated with MM, HIF1A is the most widely studied (59,60). Hypoxia, a central characteristic for cancer incidence and progression, occurs when most types of cancer are evolving (59)(60)(61)(62)(63)(64). HIF1A is a hypoxia-inducible factor, and constitutive expression of HIF1A in MM indicates that suppression of HIF1A-mediated transcription could become a favorable target for MM (65)(66)(67)(68).…”

Ablation of ATG4B Suppressed Autophagy and Activated AMPK for Cell Cycle Arrest in Cancer Cells

“…AMPK is activated and serves as an energy sensor to control cell cycle progression and autophagy in cells under nutrient deprivation or stressed conditions [30, 31]. AMPK not only directly phosphorylates cyclin-dependent kinase inhibitor p27 kip1 at Thr198 to stabilize p27 kip1 in the nucleus but also indirectly activates FoxO3a to induce p27 kip1 expression, which, in turn, arrests the cell cycle at G 1 phase [25, 30].…”

Thymoquinone Attenuates Myocardial Ischemia/Reperfusion Injury Through Activation of SIRT1 Signaling

“…The underlying mechanism of I/R injury is complicated and unclear, and may be related to factors such as mitochondrial dysfunction, overproduction of reactive oxygen species (ROS), reduction of nitric oxide bioavailability, and intracellular calcium overload [3,4]. Recently, a study has shown that shock wave therapy may serve as an effective option for ischemic heart disease [5]. Nevertheless, no effective therapy for preventing reperfusion injury is available to date [6]; thus, further study is urgently needed.…”