1 Vascular Cell Biology

Question 1

What are the main functions of the microvascular capillary bed?

Answer 1

To maintain quality/volume of ECF and keep cells alive (cells must reside <200 um from a capillary!)

Question 2

What are the 3 “tunics” of a blood vessel wall?

Answer 2

1. Tunica adventitia (outer)
   *Connective tissue
2. Tunica media (most variable)
   *Smooth muscle cells and connective tissue
3. Tunica intima (inner)
   *Continuous endothelium

Question 3

What type of cells make up the tunica intima?

Answer 3

Simple squamous endothelial cells with a basal lamina

**1% of ECs turnover every day (an active tissue)

Question 4

What are the 3 “tunics” of the heart?

Answer 4

1. adventitia= epicardium
   *simple squamous
2. media= myocardium (muscular part)
   *myocytes and fibroblasts attach to a dense connective tissue “skeleton”
3. intima= endocardium (single cell thick)
   *simple squamous

Question 5

Describe the development of epicardial cells

Answer 5

During development, epicardial cells grow over the surface of the heart as a thin, mono-cellular covering and give rise to…

1. cardiac fibroblasts
2. coronary arteries (endothelial cells, SMCs)
3. possibly cardiac myocytes

(epicardial cells labelled blue in photo)

Question 6

Describe the wall of a large artery

Answer 6

“Elastic”;

• adventitia= external elastic membrane
• media= thickest, circular SMCs with elastic lamellae (lamellae increase with age, hypertension)
• intima= continuous ECs (tight junctions and pinocytotic vesicles)

Question 7

What is the function of large arteries?

Answer 7

Elastic recoil to maintain BP during diastole

**Clinical= aneurysms

Question 8

Describe the wall of large veins

Answer 8

• thin wall
• adventitia= thickest tunic

Question 9

Describe the wall of medium arteries

Answer 9

“Muscular”;

• adventitia= nondescript
• media= prominent (~40 layers SMCs, less elastin than large arteries)
• intima- internal elastic lamina

Question 10

What is the function of medium arteries?

Answer 10

Function= SMCs regulate BP

**Clinical= atherosclerosis

Question 11

What causes atherosclerosis?

Answer 11

**Intimal plaques caused by “foam cells”

• Macrophages ingest LDL (bad cholesterol)
• SMCs migrate to the intima and ingest LDL
• Ingestion of LDL causes histological “foam” look
• Plaques calcify, platelets attach -> thrombus -> MI/stroke

Question 12

Describe the wall of medium veins

Answer 12

Like large veins but smaller (thin walled)

Question 13

Describe the wall of small arteries/arterioles

Answer 13

• In the capillary bed
• tunica media
  
  • ~8 layers SMCs in small artery
  • ~2 layers SMCs in arterioles
• lined with at least one EC

Question 14

What is the function of small arteries/arterioles?

Answer 14

SMCs regulate bloodflow to the capillary bed

**Clinical= lipid uptake by SMCs narrows the lumen -> hypertension

Question 15

Describe a capillary

Answer 15

• lumen diameter ~1 RBC (7.5 um)
• 1 endothelial cell can make up this tube
• simple squamous endothelium with basal lamina
  
  • no media, no adventitia

Question 16

What are the 3 types of capillaries?

Answer 16

1. continous
   *tight junctions (pass <10 kDa proteins)
   *pinocytic vesicles (pass >10 kDa proteins but not present in the CNS; BBB)
2. fenestrated
   *100 nm ‘windows’= permanent pinocytotic vesicles (pass >10 kDa proteins)
3. sinusoidal
   *discontinuities between ECs
   *larger than type I and II; ~30um diameter and can pass entire cells

Question 17

Describe a type I capillary

Answer 17

Continuous;

• tight junctions (pass <10 kDa proteins)
• pinocytic vesicles (pass >10 kDa proteins but not present in the CNS; BBB)
• transport oxygen

**Found in CNS, heart, skeletal muscle, lungs

Question 18

Describe a type II capillary

Answer 18

Fenestrated;

• 100 nm ‘windows’= permanent pinocytotic vesicles
  
  • pass >10 kDa proteins
  • e.g. hormones, nutrients, ions

**Found in endocrine glands, GI tract, kidneys

Question 19

Describe a type III capillary

Answer 19

Sinusoidal;

• discontinuities between ECs
• larger than type I and II; ~30um diameter and can pass entire cells

**Found in bone marrow, spleen, liver

Question 20

What are the general functions of endothelial cells?

Answer 20

• exchange gases and nutrients
  
  • gases through cell membrane
  • nutrients through pinocytotic vesicles, fenestrations and discontinuities
• secrete regulatory molecules
  
  • vasoactive factors
  • growth factors

Question 21

What are some regulatory molecules secreted by endothelial cells?

Answer 21

• vasoactive factors
  
  • endothelin (vasoconstrictor)
  • NO (vasorelaxant)
• growth factors (activate angiogenesis)
  
  • FGF: fibroblast growth factor
  • PDGF: platelet derived growth factor
  • VEGF: vascular endothelial growth factor

Question 22

What are the steps of angiogenesis?

Answer 22

• 1= activation of EC receptors
• 2-6= outgrowth and migration
• 7= inhibition of angiogenic growth

Question 23

What is the difference between angiogenesis and vasculogenesis?

Answer 23

• angiogenesis= new vessels from existing BVs in the adult
• vasculogenesis= embryonic BV development

Question 24

What are some angiogenic activators and inhibitors?

Answer 24

• activators (target ECs)
  
  • VEGF
  • FGF
  • Angiopoietin-1 (binds TIE-2 receptor)
• inhibitors
  
  • Angiostatin (endogenous)
  • Endostatin (endogenous)
  • Avastin (mAb for cancer to reduce VEGF and “starve” tumors of their blood supply)

Question 25

How are pro-angiogenic compounds used in clinical therapy?

Answer 25

For ischemia in heart and extremities

(BV growth induced by VEGF and FGF)

Question 26

How are anti-angiogenic compounds used in clinical therapy?

Answer 26

To combat tumors

(Angiostatin and endostatin inhibit new BV growth… proven in mice but unsuccessful so far in humans)