Related Experiment Video
Updated: Jun 2, 2026
08:58
En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries
Published on: February 25, 2016
Nitric oxide-donating statin improves multiple functions of circulating angiogenic cells
G Mangialardi1, A Monopoli, E Ongini
1Chair Experimental Cardiovascular Medicine, University of Bristol, Bristol, UK.
British Journal of Pharmacology
|April 14, 2011
Summary
NO-releasing atorvastatin (NCX 547) significantly improved circulating angiogenic cell (CAC) functions, especially under high glucose conditions, outperforming standard atorvastatin. This suggests NO-donating statins offer enhanced cardiovascular disease prevention strategies.
Area of Science:
- Cardiovascular Research
- Cell Biology
- Pharmacology
Background:
- Statins are crucial for cardiovascular disease prevention, supporting progenitor cell functions.
- Novel statins with NO-releasing moieties aim for enhanced anti-inflammatory and anti-thrombotic effects.
Purpose of the Study:
- To investigate the impact of NO-donating atorvastatin (NCX 547) on the functions of circulating angiogenic cells (CACs).
Main Methods:
- CACs from healthy volunteers and type-2 diabetic patients were cultured under low/high glucose with atorvastatin or NCX 547.
- Functional assays assessed outgrowth, proliferation, viability, senescence, and apoptosis, with NO inhibition/scavenging.
Main Results:
- High glucose impaired CACs; NCX 547 fully restored NO levels and functions, unlike atorvastatin which only prevented apoptosis.
- NCX 547 enhanced Akt activity in both glucose conditions, while atorvastatin's effect was glucose-dependent.
- NCX 547 improved CAC functions and migration in type-2 diabetic patients.
Conclusions:
- NCX 547 demonstrates superior efficacy over atorvastatin in preserving CAC functions.
- NO-releasing statins represent a promising therapeutic advancement for cardiovascular disease management.
Related Concept Videos
01:28Nitric Oxide Signaling Pathway
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 to...
01:24Regulation of Angiogenesis and Blood Supply
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 hydroxylase and factor...
01:10Mechanism of Angiogenesis
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
01:23Antihypertensive Drugs: Vasodilators
Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
01:16Antianginal Drugs: Nitrates and β-Blockers
In cardiovascular health, antianginal drugs combat angina pectoris — a condition marked by chest pain owing to diminished blood flow to the heart.
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow. Administered...
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow. Administered...
01:21Paracrine Signaling
Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. Nitric oxide as a...