Vascular Biology

Question 0

Do endothelial cells respond to changes in shear stress and pressure?

Answer 0

Yup.

Question 1

Where does the blood pressure vary the most?

Answer 1

In large arteries.

Question 2

4 vasodilation factors?

Answer 2

NO
Prostacyclin (PGI2)
Bradykinin
Acetylcholine

Question 3

What’s interesting about the effect of ACh on vascular tone?

Answer 3

If the endothelium is present, ACh causes dilation.

If the endothelium is disrupted, ACh causes constriction.

Question 4

How do ACh, bradykinin, and beta-2 agonists cause vasodilation?

Answer 4

By stimulating eNOS in endothelial cells to make NO.

NO then acts on smooth muscle cells.

Question 5

Why does ACh cause smooth muscle cells to constrict, if the endothelium isn’t present?

Answer 5

ACh binds to muscarinic receptors on smooth muscle cells -> contraction.
Normally, though, this effect is overwhelmed by the NO produced by endothelial cells in response to ACh.

Question 6

How does Angiotensin Converting Enzyme (ACE) affect vascular tone? So what if you give an ACE inhibitor?

Answer 6

Bradykinin relaxes vessels.
ACE breaks down bradykinin -> less relaxation.
Angiotensin II (A-2) constricts vessels.
ACE converts A-1 to A-2 -> more constriction.
ACE inhibitors lower blood pressure.

Question 7

4 factors that cause vasoconstriction?

Answer 7

Endothelin
Angiotensin II (A-2)
Thromboxane A2
ACh (in damaged blood vessels!, eg. atherosclerosis)

Question 8

Normally people’s blood vessels dilate in response to ischemia (such as from blood pressure cuff). But this doesn’t happen when there’s endothelial dysfunction.

Answer 8

cool

Question 9

6 risk factors for endothelial dysfunction?

Answer 9

Hypercholesterolemia
Cigarette smoking
Hypertension
Being male
Being older
Family Hx

Question 10

Might high-fat diet induced endothelial dysfunction have something to do with oxidation?

Answer 10

Yeah… (but I don’t think taking lots of antioxidants has been shown to increase longevity)

Question 11

2 instances when you really need angiogenesis to happen? What’s one condition where this doesn’t work well?

Answer 11

Fracture healing or other wound healing.
Ischemia due to obstruction.
In diabetes, angiogensis is impaired, making these things (and recovery from MI) worse.

Question 12

What does VEGF act upon to make vessels proliferate?

Answer 12

Endothelial progenitor cells.

Question 13

What is Hereditary Hemorrhagic Telangectasia (HHT)?

Answer 13

Autosomal dominant condition (defect in Eng or ALK1) that disrupts the control of vessel growth/repair by TGF-beta.

Question 14

3 consequences of HHT?

Answer 14

Bleeding, esp GI.
Arteriovenous malformations - causing right to left shunting of blood and “paradoxical emboli.”
Infection from septic emboli from veins (eg. endocarditis).

Question 15

2 pro-clot factors mentioned here?

Answer 15

PAI-1 (inhibits t-PA)

A-2 (stimulates PAI-1)

Question 16

What’s Virchow’s Triad?

Answer 16

Three factors that make thrombosis likely:
Hypercoaguable state.
Endothelial injury.
Circulatory stasis.

Question 17

As general, but not absolute rule, are each venous and arterial clots more about fibrin or platelets?

Answer 17

Venous: more about fibrin
Arterial: more about platelets

Question 18

2 ways in which dysfunctional endothelium leads to a more coagulable state?

Answer 18

Increased vWF -> more platelet aggregation.

Increased PAI-1 -> less t-PA, fibrinolysis.

Question 19

3 molecules for leukocyte adhesion?

Answer 19

ICAM-1 (inducible)
ICAM-2 (constituitive)
VCAM-1 (inducible)

Question 20

3 inflammation-related / adhesion molecules that A-2 promotes in blood vessels?

Answer 20

Endothelial cells -> VCAM-1 expression
NFkB -> MCP-1
Smooth muscle cells -> IL-6 -> CRP

Question 21

What adhesion molecule seems to important for bringing immune cells to fat deposits in arteries?

Answer 21

VCAM-1

and it’s induced by hyperlipidemia

Question 22

What does turbulent flow have to do with immune cells?

Answer 22

It’s easier for immune cells to stick to blood vessel walls when there’s turbulent flow.

Question 23

4 things that fuel the endothelial dysfunction of atherosclerosis?

Answer 23

Lipids (oxidized LDL)
Tobacco
Hypertension
Diabetes