Related Experiment Video
Updated: Nov 22, 2025
12:03
Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
Published on: June 7, 2016
18.2K
A role for aldehyde dehydrogenase (ALDH) 2 in angiotensin II-mediated decrease in angiogenesis of coronary
Bipradas Roy1, Suresh Selvaraj Palaniyandi1
1Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, United States of America; Department of Physiology, Wayne State University, Detroit, MI 48202, United States of America.
Microvascular Research
|January 11, 2021
Summary
Aldehyde dehydrogenase 2 (ALDH2) activation improves coronary angiogenesis impaired by Angiotensin II (Ang II) in diabetes. ALDH2 reduces 4-hydroxy-2-nonenal (4HNE) toxicity, protecting against diabetic heart disease.
Area of Science:
- Cardiovascular Biology
- Endothelial Cell Function
- Diabetic Cardiometabolic Diseases
Background:
- Diabetes causes coronary endothelial cell (CEC) dysfunction, contributing to heart disease.
- Angiotensin II (Ang II) is elevated in diabetes, increasing oxidative stress in CECs.
- Aldehyde dehydrogenase 2 (ALDH2) detoxifies 4-hydroxy-2-nonenal (4HNE), mitigating proteotoxicity and enhancing cytoprotection.
Purpose of the Study:
- To investigate if ALDH2 activation can ameliorate Angiotensin II-induced defective CEC angiogenesis.
- To determine the role of 4HNE-mediated cytotoxicity in Ang II-induced CEC dysfunction.
- To evaluate ALDH2 as a therapeutic target for improving coronary angiogenesis in cardiometabolic diseases.
Main Methods:
- Cultured mouse CECs (MCECs) were treated with Ang II, ALDH2 activator (Alda-1), ALDH2 inhibitors (disulfiram/ALDH2 siRNA), or receptor blockers (Losartan/PD0123319).
- In vitro angiogenesis assay was performed to assess tube formation.
- Levels of vascular endothelial growth factor receptors (VEGFR1/2), angiotensin II type-2 receptor (AT2R), and 4HNE-adducts were measured.
Main Results:
- Ang II significantly decreased MCEC tube formation, downregulated VEGFR1/VEGFR2, and upregulated AT2R and 4HNE-adducts.
- ALDH2 inhibition exacerbated Ang II-induced angiogenesis impairment, while AT2R inhibition improved it.
- Alda-1 (ALDH2 activator) rescued Ang II-induced angiogenesis reduction by modulating VEGFR1, VEGFR2, and AT2R levels.
Conclusions:
- ALDH2 activation is a promising therapeutic strategy to improve coronary angiogenesis.
- ALDH2 mitigates 4HNE-induced proteotoxicity and enhances CEC function in the context of Ang II signaling.
- Targeting ALDH2 may offer a novel approach to treating diabetic heart complications.
Related Concept Videos
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
2.0K
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...
2.0K
01:25Antihypertensive Drugs: Direct Renin Inhibitors
1.0K
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,...
1.0K
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
2.1K
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...
2.1K
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
672
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...
672
01:29Hypertension II: Pathophysiology
356
Hypertension is a chronic condition in which the blood's force against artery walls is excessively high, posing risks such as heart disease. The condition's underlying mechanisms involve complex interactions among the cardiovascular, kidney, and autonomic nervous systems.Renin-Angiotensin-Aldosterone System (RAAS): This system significantly influences blood pressure regulation. When blood pressure decreases, the kidneys secrete renin. This enzyme transforms angiotensinogen, a plasma protein,...
356
01:24Regulation of Angiogenesis and Blood Supply
3.1K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.1K