Trehalose-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction.

BACKGROUND: Trehalose (TRE) is a natural, nonreducing disaccharide synthesized by lower organisms. TRE exhibits an extraordinary ability to protect cells against different kinds of stresses through activation of autophagy. However, the effect of TRE on the heart during stress has never been tested. OBJECTIVES: This study evaluated the effects of TRE administration in a mouse model of chronic ischemic remodeling. METHODS: Wild-type (WT) or beclin1+/- mice were subjected to permanent ligation of the left anterior descending artery (LAD) and then treated with either placebo or trehalose (1 mg/g/day intraperitoneally for 48 h, then 2% in the drinking water). After 4 weeks, echocardiographic, hemodynamic, gravimetric, histological, and biochemical analyses were conducted. RESULTS: TRE reduced left ventricular (LV) dilation and increased ventricular function in mice with LAD ligation compared with placebo. Sucrose, another nonreducing disaccharide, did not exert protective effects during post-infarction LV remodeling. Trehalose administration to mice overexpressing GFP-tagged LC3 significantly increased the number of GFP-LC3 dots, both in the presence and absence of chloroquine administration. TRE also increased cardiac LC3-II levels after 4 weeks following myocardial infarction (MI), indicating that it induced autophagy in the heart in vivo. To evaluate whether TRE exerted beneficial effects through activation of autophagy, trehalose was administered to beclin 1+/- mice. The improvement of LV function, lung congestion, cardiac remodeling, apoptosis, and fibrosis following TRE treatment observed in WT mice were all significantly blunted in beclin 1+/- mice. CONCLUSIONS: TRE reduced MI-induced cardiac remodeling and dysfunction through activation of autophagy.

Boosting autophagy in the diabetic heart: a translational perspective.

Diabetes, obesity, and dyslipidemia are main risk factors that promote the development of cardiovascular diseases. These metabolic abnormalities are frequently found to be associated together in a highly morbid clinical condition called metabolic syndrome. Metabolic derangements promote endothelial dysfunction, atherosclerotic plaque formation and rupture, cardiac remodeling and dysfunction. This evidence strongly encourages the elucidation of the mechanisms through which obesity, diabetes, and metabolic syndrome induce cellular abnormalities and dysfunction in order to discover new therapeutic targets and strategies for their prevention and treatment. Numerous studies employing both dietary and genetic animal models of obesity and diabetes have demonstrated that autophagy, an intracellular system for protein degradation, is impaired in the heart under these conditions. This suggests that autophagy reactivation may represent a future potential therapeutic intervention to reduce cardiac maladaptive alterations in patients with metabolic derangements. In fact, autophagy is a critical mechanism to preserve cellular homeostasis and survival. In addition, the physiological activation of autophagy protects the heart during stress, such as acute ischemia, starvation, chronic myocardial infarction, pressure overload, and proteotoxic stress. All these aspects will be discussed in our review article together with the potential ways to reactivate autophagy in the context of obesity, metabolic syndrome, and diabetes.

Thigh Abscess Caused by Yersinia enterocolitica in an Immunocompetent Host.

Yersinia enterocolitica is primarily a gastrointestinal tract pathogen known to cause gastroenteritis, although it may produce extra-intestinal infections like sepsis and its sequelae. However, primary cutaneous infections are extremely rare. We present a case of Y. enterocolitica thigh abscess in an immunocompetent adult. The portal of entry is unclear in this case. He did many outdoor activities that involved skin injuries and exposure to soil and contaminated water. Hence, direct inoculation as a result of exposure to contaminated water is postulated in the absence of evidence for a gastrointestinal route of infection.

Atrial Coronary Arteries: Anatomy And Atrial Perfusion Territories.

Coronary anatomy has traditionally focused on ventricular circulation. This is largely due to the extent to which coronary artery disease contributes to ischemic heart disease through ventricular myocardial damage. Atrial fibrillation and other tachyarrhythmias that involve the atria, however, remain a major cause of morbidity and mortality. In order to increase mechanistic research and therapeutic interventional procedures for diseases of the atria, an optimal knowledge of atrial anatomy is necessary. While substantial clarity exists regarding the distribution of nerve terminals and the organization of muscle bundles, the anatomy of coronary atrial circulation remains understudied. Historically, the high anatomical variability of atrial coronary branches led to unstandardized nomenclature in the literature. In this review, we delineate the anatomic courses of key atrial coronary branches and their perfusion territories, clarify their nomenclature, and propose unifying anatomical concepts of atrial circulation that we believe to be critical to the success of modern electrophysiologic and surgical procedures.