对β细胞ER压力CHOP及其在HFpEF发展中的作用的新见解
Balaji Srinivas1, Paula Fortuno1, Hongmei Peng2,3
1Department of Physiological Sciences, EVMS, Macon & Joan Brock Virginia Health Sciences at Old Dominion University, Norfolk, VA, 23501, USA.
Cardiovascular diabetology
|June 13, 2025
概括
在b细胞中删除C/EBP同源蛋白 (CHOP) 可以保护心力衰竭以保存喷射分数 (HFpEF). 这一发现表明,针对b细胞中的CHOP可能是HFpEF的新治疗策略.
科学领域:
- 心血管研究研究心血管研究
- 代谢障碍 代谢障碍 代谢障碍
- 细胞生物学 细胞生物学
背景情况:
- 保持喷射分数的心力衰竭 (HFpEF) 是一种复杂的心血管疾病,与腹功能障碍,高血压和代谢问题有关.
- 在B细胞内C/EBP同源蛋白 (CHOP) 在HFpEF发育中的作用在很大程度上仍未被探索.
研究的目的:
- 调查b细胞C/EBP同源蛋白 (CHOP) 与心力衰竭与保留射出分数 (HFpEF) 的病变发生之间的相互关系.
主要方法:
- 雄性小鼠具有浮或CHOP删除的b细胞,在5周内接受标准饮食或高脂肪饮食与L-NAME相结合.
- 进行了全面的心血管,代谢和组织学评估,以评估HFpEF发育和相关病理.
主要成果:
- 具有功能性b细胞CHOP的小鼠出现了HFpEF的表现,包括腹功能障碍,高血压,心脏缩,纤维化和血管内皮功能障碍.
- 缺乏b细胞CHOP的小鼠受到HFpEF的保护,表现为改善心脏和血管功能,减少炎症,减弱未折叠蛋白质反应标志物.
结论:
- 在b细胞中删除未折叠的蛋白质反应CHOP,可以显著地保护心血管系统免受HFpEF的侵害.
- 准b细胞CHOP是一个有前途的治疗途径,可以缓解HFpEF的病原性.
相关概念视频
Cell Specific Gene Expression
13.5K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.5K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.2K
The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
Insulin and C-peptide are...
1.2K
Feedback Loops
57.4K
In most cases, excessive hormone production is prevented by negative feedback—a loop that starts with a stimulus inducing the release of a particular substance, like a hormone, to maintain a certain level before triggering a signal that results in a decrease in further release of the hormone.
57.4K
Hormones Regulating Blood Glucose
3.2K
Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
In addition to accelerating glucose uptake and utilization, insulin has...
3.2K
Cells and Secretions of the Pancreas
2.1K
The pancreas, a vital organ within the abdominal cavity, plays dual roles in the digestive and endocrine systems, collaborating with exocrine and endocrine cells to maintain optimal digestion and blood sugar levels.
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
Concurrently, the dispersed clusters of endocrine cells throughout the...
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
Concurrently, the dispersed clusters of endocrine cells throughout the...
2.1K
Hypothalamic-Pituitary Axis
59.7K
The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
59.7K


