瑞诺丁受体泄漏在循环B淋巴细胞中作为心力衰竭中的生物标志物
Alexander Kushnir1,2, Gaetano Santulli1, Steven R Reiken1
1Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York (A.K., G.S., S.R.R., A.R.M.).
Circulation
|March 30, 2018
概括
充血性心力衰竭 (CHF) 涉及B淋巴细胞中泄漏的RyR1通道,表明细胞内Ca2+泄漏. 测量B淋巴细胞的泄漏提供了一个新的生物标志物来监测CHF治疗的有效性.
科学领域:
- 心脏病学 心脏病学
- 生物化学 生物化学
- 细胞生物学 细胞生物学
背景情况:
- 充血性心力衰竭 (CHF) 管理需要生物标志物来监测疾病.
- 在CHF中提升的甲醇胺重塑心脏的诺丁受体,导致Ca2+泄漏和收缩能力降低.
- 这种Ca2+泄漏也通过RyR1影响骨肌肉,导致软弱.
研究的目的:
- 研究B淋巴细胞作为细胞内Ca2+处理缺陷的替代体.
- 评估CHF患者和动物模型的B淋巴细胞中的RyR1通道功能和Ca2+泄漏.
- 探索B-淋巴细胞Ca2+泄漏的潜力,作为CHF治疗的生物标志物.
主要方法:
- 从人类CHF患者,使用左心室辅助装置的CHF患者和对照组收集血液.
- 从患有缺血性CHF的小鼠收集血液,用S107治疗,以及野生类型的对照.
- 在B淋巴细胞中评估了RyR1宏分子复合体和RyR1介导的Ca2+泄漏,使用免疫染和流细胞计.
主要成果:
- 来自人类和患有慢性心血管衰竭的小鼠的B淋巴细胞显示了重塑的RyR1和减少了内分泌网膜的Ca2+储量,表明慢性Ca2+泄漏.
- 这种Ca2+泄漏与循环中的甲基荷胺水平相关.
- 用S107治疗显著减少了小鼠的Ca2+泄漏;人类对LVAD的反应异质.
结论:
- 在CHF中,B淋巴细胞表现出重塑,泄漏的RyR1通道和减少的Ca2+储量,反映出慢性细胞内Ca2+泄漏.
- 对RyR1-介导的B淋巴细胞中Ca2+泄漏的流细胞计评估作为细胞内Ca2+处理和交感负担的替代品.
- 这为监测对药物和机械CHF疗法的反应提供了一个新的生物标志物.
相关概念视频
Heart Failure II: Pathophysiology
1.0K
Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
1.0K
Pathophysiology of Heart Failure
4.0K
Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
4.0K
Heart Failure I: Introduction
951
Heart failure refers to a clinical syndrome caused by structural or functional cardiac disorders that prevent the heart from pumping an adequate amount of blood to meet the body's metabolic needs. This condition often arises from myocardial infarction or ischemia, leading to decreased cardiac output, reduced tissue perfusion, impaired gas exchange, fluid volume imbalance, and decreased functional ability.Heart failure can result from disruptions in the mechanisms that regulate cardiac output...
951
Heart Failure VI: Adjunct Therapies
395
Additional therapies for treating patients with heart failure (HF) may include procedural interventions, supplemental oxygen, the management of sleep disorders, and nutritional therapy.Procedural InterventionsImplantable Cardioverter-Defibrillator: For patients at risk of life-threatening arrhythmias due to severe left ventricular dysfunction, an Implantable Cardioverter-Defibrillator (ICD) can detect and terminate these arrhythmias, preventing sudden cardiac death and improving survival rates.
395
Heart Failure Drugs: Diuretics
1.0K
Heart failure and kidney perfusion are interconnected in a complex way. Reduced renal perfusion and venous congestion are two significant factors that contribute to renal dysfunction in heart failure. The kidneys, primarily responsible for fluid balance in the body, are adversely affected due to compromised cardiac output and increased venous pressure. In response to reduced renal perfusion, the kidneys activate neurohumoral mechanisms to restore balance. However, these mechanisms can be...
1.0K
Heart Failure V: Medical Management
360
Medical Management of Acute Decompensated Heart Failure (ADHF)The primary goals of therapy for patients hospitalized with acute decompensated heart failure (ADHF) include:Relieving symptomsOptimizing volume statusSupporting oxygenation and ventilationMaintaining cardiac output (CO) and end-organ perfusionIdentifying and addressing the cause of ADHFPreventing complicationsProviding patient education on factors precipitating HF exacerbationPlanning for dischargeOngoing monitoring and assessment...
360


