OBJECTIVEAutophagy is a critical cellular system for removal of aggregated proteins and damaged organelles. Although dysregulated autophagy is implicated in the development of heart failure, the role of autophagy in the development of diabetic cardiomyopathy has not been studied. We investigated whether chronic activation of the AMP-activated protein kinase (AMPK) by metformin restores cardiac function and cardiomyocyte autophagy in OVE26 diabetic mice.RESEARCH DESIGN AND METHODSOVE26 mice and cardiac-specific AMPK dominant negative transgenic (DN)-AMPK diabetic mice were treated with metformin or vehicle for 4 months, and cardiac autophagy, cardiac functions, and cardiomyocyte apoptosis were monitored.RESULTSCompared with control mice, diabetic OVE26 mice exhibited a significant reduction of AMPK activity in parallel with reduced cardiomyocyte autophagy and cardiac dysfunction in vivo and in isolated hearts. Furthermore, diabetic OVE26 mouse hearts exhibited aggregation of chaotically distributed mitochondria between poorly organized myofibrils and increased polyubiquitinated protein and apoptosis. Inhibition of AMPK by overexpression of a cardiac-specific DN-AMPK gene reduced cardiomyocyte autophagy, exacerbated cardiac dysfunctions, and increased mortality in diabetic mice. Finally, chronic metformin therapy significantly enhanced autophagic activity and preserved cardiac functions in diabetic OVE26 mice but not in DN-AMPK diabetic mice.CONCLUSIONSDecreased AMPK activity and subsequent reduction in cardiac autophagy are important events in the development of diabetic cardiomyopathy. Chronic AMPK activation by metformin prevents cardiomyopathy by upregulating autophagy activity in diabetic OVE26 mice. Thus, stimulation of AMPK may represent a novel approach to treat diabetic cardiomyopathy.
We report a case of coronary slow flow phenomenon (CSFP) in a patient who underwent coronary angiography due to anginal chest pain, and recurrent syncope with complete normalization of flow after intracoronary adenosine. The patient was noted to have multiple episodes of nonsustained ventricular tachycardia (VT) on holter monitor and increased QTc dispersion on surface electrocardiogram (ECG). He responded very well to oral dipyridamole therapy with complete resolution of his symptoms and no episodes of VT on the event recorder at 3 mo. We reviewed the diagnosis and clinical features of CSFP and its association with increased QTc dispersion, and the role of oral dipyridamole therapy in this condition.
The quantum Hall effect (QHE) is traditionally considered to be a purely two-dimensional (2D) phenomenon. Recently, however, a three-dimensional (3D) version of the QHE was reported in the Dirac semimetal ZrTe5. It was proposed to arise from a magnetic-field-driven Fermi surface instability, transforming the original 3D electron system into a stack of 2D sheets. Here, we report thermodynamic, spectroscopic, thermoelectric and charge transport measurements on such ZrTe5 samples. The measured properties: magnetization, ultrasound propagation, scanning tunneling spectroscopy, and Raman spectroscopy, show no signatures of a Fermi surface instability, consistent with in-field single crystal X-ray diffraction. Instead, a direct comparison of the experimental data with linear response calculations based on an effective 3D Dirac Hamiltonian suggests that the quasi-quantization of the observed Hall response emerges from the interplay of the intrinsic properties of the ZrTe5 electronic structure and its Dirac-type semi-metallic character.
Dissipationless current in topologically protected states is promising for disorder-tolerant electronics and quantum computation. Here, we show giant anisotropic terahertz (THz) photocurrents with vanishing scattering driven by femtosecond laser-induced coherent phonons of broken inversion symmetry (IS) in a centrosymmetric Dirac material ZrTe 5 . Our work suggests that this phononic THz symmetry switching leads to Weyl point (WP) formation,
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