Vascular Biology Flashcards
As arteries get smaller the velocity increases/decreases.
decreases –> cross sectional area –> promotes nutrient exchange
The amount of work that must be done to overcome friction between adjacent layers of fluid sliding over each other
shear force
Dilation of blood vessel after a period of ischemia is called:
hyperemia
Arteries that carry blood from the aorta to branch arteries
conduit arteries
Arterioles vasoconstrict/vasodilate in response to ischemia
vasodilate
Do large conduit arteries vasodilate to ischemia?
yes: 12-15%
4 molecules that promote vasodilation
NO/EDRF, prostacyclin (PGI2), bradykinin, acetylcholine
How does NO lead to vasodilation?
L-arginine is involved in production of eNOS (endothelial NO synthase) –> NO diffuses into smooth muscle cell –> activation of cGMP
How does Ach, substance P, bradykinin, B2 agonists lead to vasodilation?
G protein calmodulin pathway –> production of eNOS –> NO diffusion to smooth muscle cell –> cGMP
2 effects of ACh on blood vessels
- stimulates release of NO from endothelium leading to vasodilation
- vasoconstriction/contraction in circumstances with low NO (e.g. damaged endothelium) or with high doses of ACh (even low levels of ACh can cause constriction in diseased arteries)
High ACh + low NO causes vasoconstriction/dilation
vasoconstriction
Which is more potent? NO or PGI2
NO
Angiotensin is a vasoconstrictor/dilator
constrictor –> breaks down bradykinin thereby preventing vasodilation by reducing production of NO and and PGI2
A high fat diet impairs endothelial mediated vasodilation/vasoconstriction for up to four hours after eating.
vasodilation
What is the difference between an angioblast and an endothelial progenitor cell?
angioblast is in utero and epc is what is modified during adulthood to create new vessels –> all under control of VEGF
What factors stabilize growing blood vessels?
angiopoetin 1 and ephrin b2
What are 3 important growth factors for vessels?
pdgf, tgf beta, fgf
What growth factor can destabilize growing vessels leading to possible tumorigenesis?
angiopoetin 2
EPCs from patients with type II diabetes mellitus are characterized by:
decreased proliferation capacity and reduction of their adhesiveness and ability to form capillary tubes in vitro
What autosomal dominant condition can result from disruption of TGF beta signalling via abnormalities in one of two genes, endoglin (Eng) and activin-receptor-like kinase-1
(ALK1)?
HHT/Osler-Weber-Rendu
4 consequences of HHT
- GI bleeding
- infection from septic emboli
- arteriovenous malformation in lungs causing shunting of blood and paradoxical emboli
- telangiectases
3 classifications of anti-clot systems
- fibrinolytic - t-PA
- antithrombin - thrombomodulin, heparin
- antiplatelet - NO, prostacyclin, ADPases
2 classifications of pro-clot systems
- anti-fibrinolytic - PAI1
2. angiotensin II stimulation of PAI1 (plasminogen activator inhibitor)
_____ cleaves fibrin to produce progressively smaller degradation products
Plasmin
Virchow’s triad
hypercoagulable state, endothelial injury, circulatory stasis –> clotting/DVT
2 procoagulable properties of dysfunctional endothelium leading
- increase vwf production with increased platelet adhesion/aggregation
- increased synthesis of PAI1 resulting in impaired fibrinolysis
All cell adhesion molecules are constitutively expressed on endothelium except:
ICAM II
Migration of neutrophils, monocytes and
lymphocytes from the circulating blood to the inflammatory sites is directed by the expression of specific _____ on the
endothelium
cell adhesion molecules
______ is a transcription factor involved in the expression of genes encoding many proinflammatory functions of
vascular wall cells and infiltrating leukocytes.
NFkB
_________ acts as a proinflammatory factor by stimulating NFkB leading to expression of
_____, which mediates monocyte adhesion and of the chemokine _____, which attracts monocytes
Angiotensin-II, VCAM-1, MCP-1
Angiotensin-II stimulates expression of
______, which provokes the acute-phase response leading to production of the systemic inflammatory marker _________..
interleukin (IL)-6, C-reactive protein
CRP
Studies in hypercholesterolemic rabbits have
shown that ____ localizes in endothelium over foam cell–filled fatty streaks in the aorta.
VCAM
T/F Endothelial leukocyte adhesion molecules play an important role in early plaque development
T
____ stimulates production of endothelial
leukocyte adhesion molecules early in atherosclerotic lesion formation
OxLDL aka oxidative fat
Spiral secondary flows and recirculation zones with lower shear stress result in round/elongated endothelial cells
round
Do blood vessels have cholinergic innervation?
no –> only muscarinic receptors
What stimulates NOS to produce NO from L-arginine?
shear stress, chemical mediateors like ACh
Name a competitive inhibitor of L-arginine that indirectly inhibits NO production
ADMA
What stimulates PGI2 release from endothelium?
shear stress, physiologic agonists, pathologic insult –> inhibits platelet activation, secretion, aggregation and maintains relaxation
Vasoconstrictor or vasodilator? TxA2
constrictor
Vasoconstrictor or vasodilator? PGI2
dilator
Vasoconstrictor or vasodilator? NO
dilator
Vasoconstrictor or vasodilator? endothelin
constrictor
Vasoconstrictor or vasodilator? ACh
constrictor
Vasoconstrictor or vasodilator? Angiotensin II
constrictor
Vasoconstrictor or vasodilator? bradykinin
dilator
Vasoconstrictor or vasodilator? substance P
dilator
Vasoconstrictor or vasodilator? superoxide anion O2-
constrictor
What happens to the number of EPCs in patients with risk factors for ischemic cardiovascular disease?
reduce number of endothelial preogenitors
