SARS-CoV-2 尖端诱导的结合细胞衰老,并导致心力衰竭恶化
Huilong Li1,2, Luming Wan1, Muyi Liu1
1Beijing Institute of Biotechnology, Beijing, China.
PLoS pathogens
|August 5, 2024
概括
在长期的COVID-19中,SARS-CoV-2尖端蛋白 (SARS-2-S) 导致细胞融合和衰老,恶化心力衰竭. 像WNK1抑制剂这样的治疗方法在COVID-19后急性后果中显示出对心脏病理的前景.
科学领域:
- 心血管生物学 心血管生物学
- 病毒学 病毒学
- 细胞衰老 细胞衰老
背景情况:
- 在长期的COVID-19中,SARS-CoV-2尖端蛋白 (SARS-2-S) 循环,可能会在未感染的细胞中引起细胞-细胞融合.
- 在COVID-19 (PASC) 后急性后果中,SARS-2-S合成,衰老和心脏功能障碍之间的联系尚不清楚.
研究的目的:
- 调查SARS-2-S诱导的结合细胞是否会导致衰老并加剧心脏病理.
- 阐明将SARS-2-S综合细胞与心力衰竭进展联系起来的分子机制.
主要方法:
- 在表达SARS-2-S (DNA等离子体,LNP-mRNA或S-EVs) 的细胞中证明了syncytium的形成和衰老.
- 研究了MAVS聚合物和TNFα在SARS-2-S同胞体衰老中的作用.
- 分析了老化合成细胞对WNK1激活和心脏新陈代谢的影响.
- 在心力衰竭的小鼠模型中测试了治疗干预措施 (WNK1抑制剂,尼古洛萨米德,达沙替尼).
主要成果:
- SARS-2-S传递方法诱导了具有衰老类型的表型的合成体.
- 含有SARS-2-S (S-EVs) 的细胞外囊泡形成了衰老的合成细胞.
- 形成SARS-2-S结合体涉及MAVS聚合物和TNFα,导致WNK1激活和心脏代谢受损.
- 在小鼠中,WNK1抑制剂WNK463,尼古胺和达沙替尼对SARS-2-S诱导的心力衰竭恶化的保护.
结论:
- SARS-2-S诱导的合成细胞促进细胞衰老并加剧心力衰竭,为COVID-19心脏病理提供了一种机制.
- 抑制WNK1是PASC中心脏功能障碍的潜在治疗策略.
更多相关视频
10:21Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
Published on: June 14, 2016
10.0K
11:00Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
Published on: September 18, 2017
10.1K
相关概念视频
Pathophysiology of Heart Failure
1.5K
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...
1.5K
Heart Failure Drugs: Inotropic Agents
548
Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
548
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
406
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
406
Imbalances in Cardiac Output
1.4K
The heart's primary function is to pump blood throughout the body, maintaining a balance between blood sent out (cardiac output) and blood returning (venous return). If this balance is disrupted, it can result in congestive heart failure (CHF), a severe condition where the heart becomes an inefficient pump, leading to inadequate blood circulation.
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
1.4K
Acute Respiratory Failure-II
192
Type I Respiratory Failure, or hypoxemic respiratory failure, occurs when the partial pressure of oxygen (PaO2) in arterial blood falls below 60 mmHg while breathing room air without a corresponding increase in arterial carbon dioxide levels (PaCO2). This condition highlights a significant impairment in the lungs' capacity to oxygenate the blood.
The underlying physiological abnormalities that contribute to hypoxemic respiratory failure include:
The underlying physiological abnormalities that contribute to hypoxemic respiratory failure include:
192
Pneumonia II: Pathophysiology
238
The pathophysiology of pneumonia involves the following steps:
238
