Theme 5: Vascular endothelial health Flashcards
(20 cards)
What is the role of endothelial cells in vascular function?
- Form a selectively permeable barrier
- Regulate vascular tone
- Control coagulation
- Mediate immune response
What are the key endothelium-derived relaxing factors (EDRF)?
- Nitric oxide (NO)
- Prostacyclin (PGI2)
- Endothelial-derived hyperpolarisation factors (EDHF)
How does nitric oxide (NO) contribute to endothelial function?
NO induces vasodilation by activating soluble guanylate cyclase (sGC), increasing cGMP levels, and reducing intracellular calcium.
How does NO prevent atherosclerosis?
NO inhibits platelet aggregation, leukocyte adhesion, and smooth muscle cell proliferation, which are key events in atherosclerosis.
What is the function of the ABCA1 transporter in macrophages?
ATP-binding cassette transporter A1 (ABCA1) is a cell membrane protein that exports excess cholesterol from cells to apolipoprotein (apo) A-I.
What are two consequences of defective ABCA1 transport in macrophages?
Defective ABCA1 transport leads to cholesteryl ester accumulation in macrophages, preventing ApoA-I conversion into pre-β HDL and promoting foam cell formation, a key driver of atherosclerosis.
Which transcription factor regulates ABCA1 expression?
Liver X Receptor (LXR).
What can be concluded from the Radjesh J. Bisoendial study on endothelial function in ABCA1 heterozygotes?
ABCA1 heterozygotes show reduced 5HT-induced vasodilation, indicating endothelial dysfunction, which is partially improved by HDL increase.
What are the four steps of leukocyte adhesion?
- Rolling – Leukocytes tether to endothelium via selectins.
- Activation – Chemokines activate leukocyte integrins.
- Firm adhesion – Integrins bind to endothelial ICAM-1 and VCAM-1.
- Transmigration – Leukocytes move through endothelial junctions.
What types of adhesion molecules are involved in the first three steps of leukocyte adhesion?
- Rolling – Selectins (P-selectin, E-selectin).
- Activation – Chemokine receptors.
- Firm adhesion – Integrins (LFA-1, VLA-4) binding to ICAM-1, VCAM-1
What are common causes of endothelial dysfunction?
- Oxidative stress
- Inflammation
- Reduced NO bioavailability
- Increased endothelin-1 (ET-1) levels
How does oxidative stress contribute to endothelial dysfunction?
Superoxide anions react with NO to form peroxynitrite, reducing NO bioavailability and leading to impaired vasodilation.
How do inflammatory cytokines affect endothelial function?
They upregulate adhesion molecules, disrupt NO-ET balance, and induce endothelial apoptosis.
What is flow-mediated dilation (FMD), and how does it assess endothelial function?
FMD measures endothelium-dependent vasodilation in the brachial artery using ultrasound before and after induced hyperaemia.
What dietary factors can improve endothelial function?
- Polyphenols (increase NO production and reduce oxidative stress)
- L-Arginine (substrate for NO synthesis)
- Omega-3 fatty acids (reduce cytokine production and enhance NO availability)
What is the role of monocytes/macrophages in atherosclerosis?
Monocytes adhere to activated endothelium, differentiate into macrophages, engulf LDL, and become foam cells, driving plaque formation.
How does cholesterol trafficking occur in macrophages?
LDL is taken up via scavenger receptors (CD36, SR-A), processed by lysosomal acid lipase (LAL), and effluxed via ABCA1 and ABCG1 transporters.
What transcription factors regulate macrophage cholesterol metabolism?
PPARs (PPARα, PPARγ, PPARβ/δ) and LXRs (LXRα, LXRβ) regulate lipid uptake, storage, and efflux.
What happens when lipid uptake exceeds efflux in macrophages?
Excess cholesterol is esterified by ACAT1 and stored as lipid droplets, forming foam cells and promoting atherosclerosis.
How does vitamin D supplementation affect endothelial function?
It may reduce inflammation, enhance NO bioavailability, and improve endothelial-dependent vasodilation.
