氧化低密度脂蛋白通过AT1-LOX1受体复合体来强化血管酶二诱导的Gq激活
Jittoku Ihara1, Yibin Huang1,2, Yoichi Takami1
1Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
eLife
|March 25, 2025
概括
氧化LDL和 ангиотензин II通过AT1-LOX1复合体协同作用,恶化损伤. 阻止这种相互作用可能为慢性病患者提供新的治疗方法,这些患者患有失脂血症和高血压.
科学领域:
- 心血管科学 心血管科学
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
背景情况:
- 慢性病 (CKD) 和动脉样硬化心脏病与失脂症和高血压有关.
- 氧化低密度脂蛋白 (oxLDL) 和血管素II (Ang II) 在损伤中起作用.
- G蛋白αq亚单元 (Gq) 信号传递与这些病理过程有关.
研究的目的:
- 为了研究oxLDL和Ang II在损伤中的相互作用.
- 为了确定oxLDL是否通过AT1-LOX1复合体增强Ang II诱导的Gq信号.
- 探索向AT1-LOX1受体复合体的治疗潜力.
主要方法:
- 利用CHO和细胞模型来评估Gq信号激活.
- 用于构造研究的AT1生物传感器.
- 在体内实验中对野生型和LOX-1淘汰赛小鼠进行了高脂肪饮食和Ang II输液的实验.
主要成果:
- 氧化LDL单独没有激活Gq信号,但在表达AT1和LOX-1的细胞中强化了Ang II诱导的信号.
- 在AT1-LOX1复合体中观察到oxLDL和Ang II之间的协同相互作用,导致异醇酸盐1的产量增加和的流入.
- 在体内,LOX-1淘汰赛小鼠显示出对Ang II诱导的功能障碍的保护,与野生型小鼠不同.
结论:
- 在CKD中功能障碍的一个新机制涉及通过AT1-LOX1复合体的oxLDL和Ang II的协同作用.
- 这种相互作用在失脂血症和高血压的背景下显著导致损伤.
- 向AT1-LOX1受体复合体为共发性CKD患者提供了潜在的治疗策略.
相关概念视频
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
560
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
560
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
430
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
430
01:09GPCRs Regulate Adenylyl Cylase Activity
5.1K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.1K
01:25Antihypertensive Drugs: Direct Renin Inhibitors
466
The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
466
01:28Nitric Oxide Signaling Pathway
4.9K
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
4.9K
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
354
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...
354