Takotsubo cardiomyopathy (also referred to as transient apical ballooning syndrome, broken heart syndrome or stress cardiomyopathy) is an increasingly recognized entity in the western world typically characterized by ...Takotsubo cardiomyopathy (also referred to as transient apical ballooning syndrome, broken heart syndrome or stress cardiomyopathy) is an increasingly recognized entity in the western world typically characterized by reversible left ventricular dysfunction that develops in the setting of acute severe emotional or physical stress. Increased catecholamine levels have been proposed to play a central role in the pathogenesis of the disease, although the specific pathophysiology of this condition remains elusive at the present moment. In recent times, there have been reports of takotsubo cardiomyopathy (TC) following medical interventions such as invasive or surgical procedures or specific medical regimens. In the current report, we present a patient with multiple recurrences of TC triggered by the same medical therapeutic intervention; in our particular case, repetitive exposure to inhaled beta-2-adrenoceptor agonist.展开更多
Upon viral infection, cytoplasmic pattern recognition receptors detect viral nucleic acids and activate the adaptor protein VISA/MAVS- or MITA/STING-mediated innate antiviral response. Whether and how the innate antiv...Upon viral infection, cytoplasmic pattern recognition receptors detect viral nucleic acids and activate the adaptor protein VISA/MAVS- or MITA/STING-mediated innate antiviral response. Whether and how the innate antiviral response is regulated by neuronal endocrine functions is unclear. Here, we show that viral infection reduced the serum levels of the β-adrenergic hormones epinephrine and norepinephrine as well as the cellular levels of their receptors ADRB1 and ADRB2. We further show that an increase in epinephrine/norepinephrine level inhibited the innate antiviral response in an ADRB1-/2-dependent manner. Mechanistically, epinephrine/norepinephrine stimulation activated the downstream kinase PKA, which catalyzed the phosphorylation of MITA at S241, S243 and T263, inhibiting MITA activation and suppressing the innate immune response to DNA virus. In addition, phosphorylation of VISA at T54 by PKA antagonized the innate immune response to RNA virus. These findings reveal the regulatory mechanisms of innate antiviral responses by epinephrine/norepinephrine and provide a possible explanation for increased host susceptibility to viral infection in stressful and anxiety-promoting situations.展开更多
文摘Takotsubo cardiomyopathy (also referred to as transient apical ballooning syndrome, broken heart syndrome or stress cardiomyopathy) is an increasingly recognized entity in the western world typically characterized by reversible left ventricular dysfunction that develops in the setting of acute severe emotional or physical stress. Increased catecholamine levels have been proposed to play a central role in the pathogenesis of the disease, although the specific pathophysiology of this condition remains elusive at the present moment. In recent times, there have been reports of takotsubo cardiomyopathy (TC) following medical interventions such as invasive or surgical procedures or specific medical regimens. In the current report, we present a patient with multiple recurrences of TC triggered by the same medical therapeutic intervention; in our particular case, repetitive exposure to inhaled beta-2-adrenoceptor agonist.
基金supported by grants from the National Natural Science Foundation of China(32188101,31830024,31922021 and 32170713)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-071).
文摘Upon viral infection, cytoplasmic pattern recognition receptors detect viral nucleic acids and activate the adaptor protein VISA/MAVS- or MITA/STING-mediated innate antiviral response. Whether and how the innate antiviral response is regulated by neuronal endocrine functions is unclear. Here, we show that viral infection reduced the serum levels of the β-adrenergic hormones epinephrine and norepinephrine as well as the cellular levels of their receptors ADRB1 and ADRB2. We further show that an increase in epinephrine/norepinephrine level inhibited the innate antiviral response in an ADRB1-/2-dependent manner. Mechanistically, epinephrine/norepinephrine stimulation activated the downstream kinase PKA, which catalyzed the phosphorylation of MITA at S241, S243 and T263, inhibiting MITA activation and suppressing the innate immune response to DNA virus. In addition, phosphorylation of VISA at T54 by PKA antagonized the innate immune response to RNA virus. These findings reveal the regulatory mechanisms of innate antiviral responses by epinephrine/norepinephrine and provide a possible explanation for increased host susceptibility to viral infection in stressful and anxiety-promoting situations.
