核二酸激酶B的缺乏导致赫索胺生物合成途径的内皮激活和心脏功能障碍
Feng Shao1, Johanna Wieland1,2, Yixin Wang1
1Experimental Pharmacology Mannheim, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Str. 13-17, 68167, Mannheim, Germany.
Cardiovascular diabetology
|February 21, 2025
概括
核酸二酸激酶B (NDPKB) 缺乏导致心脏问题,通过激活内皮细胞中胺生物合成途径 (HBP). 这导致心脏功能障碍,并强调了HBP在心血管健康中的作用.
科学领域:
- 心血管生物学 心血管生物学
- 代谢途径 代谢途径
- 细胞信号传输 细胞信号传输
背景情况:
- 内皮细胞 (ECs) 中核酸二酸酶B (NDPKB) 缺乏与胺生物合成途径 (HBP) 激活和视网膜血管损伤有关.
- 这项研究研究了NDPKB缺乏症在小鼠模型中的心脏后果.
研究的目的:
- 为了确定NDPKB缺乏对心脏功能和结构的影响.
- 阐明胺生物合成途径 (HBP) 在NDPKB缺陷心脏中的作用.
主要方法:
- 利用了缺乏NDPKB的小鼠,并通过心声学评估心脏功能.
- 使用hiPSC衍生的心肌细胞 (hiPSC-CMs) 和IonOptix系统分析心肌细胞收缩性.
- 进行免疫阻塞和免疫光,以检查心脏组织和细胞中的蛋白质表达和定位.
主要成果:
- 缺乏NDPKB的小鼠表现出葡萄糖耐受性受损,心脏缩和腹功能障碍.
- 观察到索兰本 (PLN) 的酸化降低和/内网膜Ca2+-ATPase 2 (SERCA2) 表达.
- 激活HBP和O-GlcNAc循环,以及纤维化和TGF-β上调,发生在NDPKB缺乏的心脏和心脏EC中.
结论:
- 缺少NDPKB会触发内皮HBP的激活,导致心脏功能障碍.
- 适当的内皮HBP功能对于维持心血管平衡至关重要.
相关概念视频
Notch Signaling Pathway
4.2K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.2K
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
Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
41
Cardiac biomarkers are critical in diagnosing, prognosing, and managing cardiovascular diseases. Routine measurement of specific biomarkers such as B-type natriuretic peptide (BNP), C-reactive protein (CRP), and homocysteine (Hcy) is common practice in clinical settings to evaluate heart function and predict cardiovascular events.
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
41
Electron Transport Chain: Complex I and II
10.2K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
10.2K
Long-patch Base Excision Repair
6.9K
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
6.9K
Transducer Mechanism: Enzyme-Linked Receptors
2.3K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.3K


