title: Decreased autophagy: a major factor for cardiomyocyte death induced by β1-adrenoceptor autoantibodies.
abstract: Cardiomyocyte death is one major factor in the development of heart dysfunction, thus, understanding its mechanism may help with the prevention and treatment of this disease. Previously, we reported that anti-β1-adrenergic receptor autoantibodies (β1-AABs) decreased myocardial autophagy, but the role of these in cardiac function and cardiomyocyte death is unclear. We report that rapamycin, an mTOR inhibitor, restored cardiac function in a passively β1-AAB-immunized rat model with decreased cardiac function and myocardial autophagic flux. Next, after upregulating or inhibiting autophagy with Beclin-1 overexpression/rapamycin or RNA interference (RNAi)-mediated expression of Beclin-1/3-methyladenine, β1-AAB-induced autophagy was an initial protective stress response before apoptosis. Then, decreased autophagy contributed to cardiomyocyte death followed by decreases in cardiac function. In conclusion, proper regulation of autophagy may be important for treating patients with β1-AAB-positive heart dysfunction.
authors: Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, PR China.|Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors: L
authors: L
authors: Wang
authors: Department of Orthopaedics, Shanxi Dayi Hospital (Shanxi Academy of Medical Sciences), Taiyuan, Shanxi, PR China.
authors: H
authors: H
authors: Hao
authors: Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors: J
authors: J
authors: Wang
authors: Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors: X
authors: X
authors: Wang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors: S
authors: S
authors: Zhang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors: Y
authors: Y
authors: Du
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors: T
authors: T
authors: Lv
authors: Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors: L
authors: L
authors: Zuo
authors: Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors: Y
authors: Y
authors: Li
authors: Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, PR China.|Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, PR China.
authors: H
authors: H
authors: Liu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001323:Autoantibodies / Q000008:administration & dosage*; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D009202:Cardiomyopathies / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007116:Immunization, Passive; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D051017:Apoptosis Regulatory Proteins; D001323:Autoantibodies; D000071186:Beclin-1; C512829:Becn1 protein, rat; D018342:Receptors, Adrenergic, beta-1; C025946:3-methyladenine; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D000225:Adenine; D020123:Sirolimus