Lecture C3 + C4

Question 1

cardiovascular system over time

Answer 1

-270 BC: erasistratus open-ended (air in arteries)
-170 AD: galen open-ended (air and blood in arteries; pores in heart)
-1500s: colombo open and closed (pulmonary circuit)
-1600s: harvey closed (blood in arteries)

Question 2

_____ coined the name ‘endothelia’ for epithelia that arise from the ______, and which come to line ______

Answer 2

-Wilhelm His (1831–1904)
-mesoderm
-body cavities, and the blood and lymphatic vessel

Question 3

In 1973, Eric Jaffe and colleagues did what?

Answer 3

isolated and cultured endothelial cells in vitro

Question 4

endothelial cells are cells that ____

Answer 4

line the internal surface of all components of the blood and lymphatic systems

Question 5

Ontogeny (def.)

Answer 5

the origination and development of an organism, usually from the time of fertilization of the egg to adult

Question 6

Blood islands give rise to both ______

Answer 6

vasculogenesis (process of blood vessel formation) and primitive hematopoiesis (production of all blood cells)

Question 7

Formation of endothelial cells

Answer 7

-mesodermal cells form blood islands (hemangioblasts)
-Hemangioblasts form endothelial and hematopoietic (primitive HSC) lineages

Question 8

_________ are the fundamental processes by which new blood vessels are formed.

Answer 8

Vasculogenesis and angiogenesis

Question 9

endothelial precursor cells aka _____

Answer 9

angioblasts

Question 10

Vasculogenesis (def.)

Answer 10

differentiation of endothelial precursor cells, or angioblasts, into endothelial cells and the de novo formation of a primitive vascular
network.

Question 11

Angiogenesis (def.)

Answer 11

growth of new capillaries from preexisting blood vessels either via sprouting (sprout off existing vessel) or intussusception (splitting existing blood vessel into two)

Question 12

Vasculogenesis: Angioblasts begin to differentiate into endothelial cells and assemble into tubes in response to ____ (receptor: ______) This leads to recruitment of _______ that wrap around BM of capillaries via _____

Answer 12

-VEGF signals
-Flk1, Flt1
-pericytes and smooth muscle
-several ligands and receptor interaction

Question 13

Smooth muscle/pericyte differentiation during vasculogenesis requires ____

Answer 13

TGF-B activation

Question 14

_____ is endothelial cell marker

Answer 14

Tie2

Question 15

angiogenesis: how sprouting happens?

Answer 15

extracellular VEGF gradients induce specification of endothelial tip and stalk cells
-high VEGF: tip cels
-low VEGF: stalk cells
-tip cells eventually fuse to form new lumen

Question 16

angiogenesis: how intussusception happens?

Answer 16

in absence of VEGF gradient, all endothelial cells respond to VEGF and form stalk without tip cells
-tansluminar pillar forms in the middle forming two vessels

Question 17

How can you study endothelial cells

Answer 17

-tube formation assay: put cells in plate and watch them form tubes
-scratch assay: make a scratch on a cell monolayer and capturing images at regular intervals by time lapse microscope

Question 18

Weibel-Palade bodies (WPBs) are what?

Answer 18

-large (1-6 μm long) cigarshaped secretory organelles used for post-synthesis storage in endothelial cells.

Question 19

WPB can be triggered to ____. They store factors that are essential to _____

Answer 19

-release their contents rapidly
-hemostasis, inflammation, regulate vascularity tonicity and angiogenesis

Question 20

hemostasis (def.)

Answer 20

-process to prevent and stop bleeding, first step in wound healing

Question 21

WBPs contains this that determines its cigar shape?

Answer 21

von Willebrand Factor (VWF); multimerized hemostatic protein

Question 22

VWF function

Answer 22

-adhere platelets to damaged endothelium
-allows for platelet aggregation, clot is stabilized by fibrin strands around platelet plug

Question 23

von Willebrand Factor biogenesis: ______ translocation into the ER. Dimerization through its ______. Trafficked to the _____. Triggered by changes in the lumenal milieu of the Golgi (______), the dimers rearrange themselves into so-called ______

Answer 23

-Co-translational (has furin-like cleavage site)
-cysteine knot (CK) domain located at its C-terminus
-Golgi complex
-acidic pH and Ca2+ ions
-dimeric bouquets

Question 24

vWF at the golgi, calcium and low pH promote ______. Dimers are stacked into _____

Answer 24

-vWF tubulation
-right-handed coil

Question 25

WBP is exocytosed and vWF is _____ in the event of injury to blood vessel

Answer 25

cleaved

Question 26

cardiac muscle descr.

Answer 26

-has cross-striations and is composed of elongated, branched cells bound to one another at intercalated discs=junctions -Contraction is involuntary, vigorous, and rhythmic

Question 27

smooth muscle descr.

Answer 27

-lacks striations -have slow, involuntary contractions

Question 28

skeletal muscle has no ____

Answer 28

intercalated discs

Question 29

skeletal vs. cardiac: gap junctions

Answer 29

-no -yes

Question 30

skeletal vs. cardiac: contraction regulation

Answer 30

-voluntary -involuntary

Question 31

skeletal vs. cardiac: source of Ca++

Answer 31

-sarcoplasmic reticulum (ER) -sarcoplasmic reticulum and extracellular fluid

Question 32

skeletal vs. cardiac: pacemaker

Answer 32

-no -yes

Question 33

skeletal vs. cardiac: electrical stimulation

Answer 33

-nervous system (excitation) -pacemaker (excitation); nervous system (beating frequency modulation)

Question 34

PM of muscle cell

Answer 34

sacrolemma

Question 35

cardiomyocytes descr.

Answer 35

- 15-30 μm in diameter and 85 -120 μm long - Usually only one centrally located nucleus - Joined end to end by intercalated discs (has interdigited processes)

Question 36

Junctional complexes of cardiomyocytes do what?

Answer 36

-promote rapid impulse conduction through many cells simultaneously and contraction of many adjacent cells as a unit

Question 37

The intercalated disc controls ______ of the cardiac tissue

Answer 37

electrical and mechanical coupling

Question 38

Junctional complexes contain: ______ + functions

Answer 38

-Desmosomes: adhesion -gap junctions- excitability -adherens junctions (fascia adherens)- adhesion

Question 39

In epithelia, ______ are distinct, whereas in vertebrate hearts, these junctions can become intermixed in a structure called the _____

Answer 39

-DSMs and AJs -area composita

Question 40

In the area composita, ____ is substituted by ______ in adherens junctions and the _____ interacts with _____

Answer 40

-catenin-β1 -plakoglobin (PG) -plakophilin (PKP2) -catenin-α3 (αT)

Question 41

Gap junctions do what?

Answer 41

enable passive diffusion of metabolites, water and ions between cells (electrical and metabolic communication between cells)

Question 42

Gap junctions:______, assembled to form a pore, called the______

Answer 42

-Connexins -connexon

Question 43

In cardiac muscle gap junctions ensure a ______ which triggers _____ contraction of the cardiomyocytes

Answer 43

-proper propagation of the electrical impulse -sequential and coordinated

Question 44

At resting state, the cells are _____ on the inside and _____ on the outside. During an action potential _____ ions flow in, and ____ ions flow out.

Answer 44

-more negative (K+ inside) -positive (Na+/Ca++ outside) -Ca++ and Na+ -K+

Question 45

The pacemaker cells of the _____ node fire spontaneously (~______/min).

Answer 45

-sinoatrial (SA) -80 action potentials

Question 46

Rapid communication of action potentials between pacemaker cells and contractile muscle cells happens through ______. This allows cardiac muscle fibers to work together as a _____.

Answer 46

-gap junctions -functional syncytium

Question 47

Transverse-tubules (T tubules) are ______

Answer 47

specialized sarcolemma invaginations

Question 48

Cardiac SR membranes are specialized ER domains for the _______

Answer 48

regulation of Ca2+ transport and control of excitation–contraction coupling

Question 49

The SR can be divided into at least two structural and functional domains: ______

Answer 49

the longitudinal SR and the junctional SR

Question 50

_______ are mostly concentrated in the junctional SR, where they have an important role in ______. Longitudinal SR is mainly composed of _______.

Answer 50

-Ryanodine receptors (RyR) and Ca2+ channels, and calsequestrin -Ca2+ storage and Ca2+ release to trigger muscle contraction -SERCA (sarco/endoplasmic reticulum Ca2+-ATPase)

Question 51

Ryanodine + Ryanodine receptor

Answer 51

-plant extract that is a pesticide/toxic to humans too -blocks ryanodine receptor-> block contractions -> causes paralysis

Question 52

Excitation-contraction coupling of cardiac muscle cells

Answer 52

1. Action potentials traveling along the sarcolemma and down into the T-tubule system depolarize the cell membrane. 2. L-type calcium channels open to permit calcium entry into the cell. 3. Calcium influx triggers calcium release from the SR through calcium-release channels (ryanodine receptors). This is called calcium-induced calcium release. 4. Free calcium binds to troponin-C (TN-C). This induces a conformational change in the regulatory complex, resulting in the actin and myosin filaments slide past each other. 5. Calcium is sequestered by the SR by an ATP-dependent calcium pump (SERCA), thus lowering the cytosolic calcium concentration and removing calcium from the TN-C, leading to restoration of the initial sarcomere length.

Question 53

Smooth muscle is responsible for _____ in various tissues. These contractions are relatively _____ than in skeletal or cardiac muscle

Answer 53

-involuntary contractions -slow and of greater duration

Question 54

Smooth muscle cells (descr.)

Answer 54

-long and thin with pointed ends; there are no striations -have dense bodies, plaque-like structures (IF +myofilaments) -Bundles of actin filaments are anchored to the dense bodies in a crisscross pattern; cross-bridges form in an irregular pattern

Question 55

contractions of smooth muscle cells shown by _____

Answer 55

dense bodies getting closer

Question 56

Smooth muscle contraction: In response to _____ signal, extracellular calcium enters the muscle cell activating the protein _____. The _______ complex binds to_____, activating it and triggering _______. Phosphorylation leads to a _____ in myosin, promoting its assembly into ____ and activates the cross-bridge cycle. As the calcium levels in the muscle cell fall, ____ is inactivated.

Answer 56

-nerve or hormonal -Calmodulin -calcium-Calmodulin -MLCK (myosin light chain kinase) -myosin light-chain phosphorylation -conformational change -filaments -MLCK

Question 57

Smooth muscle pathophysiology in asthma: Airway smooth muscle cells (ASM) do what?

Answer 57

thickens and hypertrophied in bronchiole

Question 58

Activation of the airway epithelium by allergens causes the _____. This leads to the recruitment of ______

Answer 58

-release of growth factors from epithelial cells -inflammatory cells which release cytokines

Question 59

Asthma: The factors from the epithelium and the inflammatory cells stimulate ______, ______, and ______, and increased production of _____. They stimulate additional production of ____ from the ASM cells that further drive increased _____.

Answer 59

-myofibroblast migration -proliferation -hypertrophy -ECM components -soluble mediators -ASM mass

Question 60

Mural cells include vessel-associated cell types such as_____ and _______. Pericytes remain a relatively _____, without highly specific markers available for their identification.

Answer 60

-pericytes -vascular smooth muscles -poorly defined cell type

Question 61

A single vSMC layer wraps around _____ and in precapillary arterioles encircles the entire _____. Pericytes investing capillaries have a nearly _______. The primary processes give rise to secondary perpendicular processes, which attach _______. On postcapillary venules vSMC cell body ______.

Answer 61

-arterioles -abluminal side of the endothelium -rounded cell body and a few primary processes -firmly to the endothelium -flattens and gives rise to many slender, branching processes

Question 62

vSMCs covering venules have a ________, which, unlike arteriolar vSMCs, do not wrap ______

Answer 62

-relatively big, stellate shape cell body with many branching processes -circularly around the endothelium

Question 63

Continuous capillaries are normally associated with perivascular contractile cells called_____

Answer 63

-pericytes

Question 64

Pericytes: They have _______ that partly surround the endothelial layer. They secrete many _____ and form their own ____, which fuses with the basement membrane of the ____

Answer 64

-long cytoplasmic processes -ECM components -basal lamina -endothelial cells

Question 65

Despite being separated by the shared basement membrane, pericytes and endothelial cells make numerous direct contacts of different type: ______

Answer 65

peg-socket contacts and adhesion plaques

Question 66

Peg-socket contacts: _______ (pegs) are inserted into ________ (pockets). The peg-socket contacts contain cell-to-cell junction proteins, such as ______

Answer 66

-pericyte cell membrane protrusion-like structures -endothelial cell membrane invaginations -N-cadherin and CX43 hemichannels (gap junctions)

Question 67

The vasculature of the CNS possesses characteristics that result in an “extreme” tightness of the vascular bed—_______—which is a functional term denoting that the healthy CNS vasculature is impermeable to the _______

Answer 67

-the blood-brain barrier (BBB) -passive transport of cells, proteins, and bioactive compounds present in the blood

Question 68

Within the CNS, ____ are important for maintaining the endothelial blood-brain barrier (BBB).

Answer 68

-pericytes

Question 69

Pericytes are integral members of the _____ (NVU). Pericytes promote tight and adherens junction formation via control of endothelial cell expression of _______(between endothelial cells).

Answer 69

-neural vascular unit -occludin and claudin-5 and VE- cadherin

Question 70

The recruitment of pericytes to the NVU can be mediated by ____ secreted by endothelial cells

Answer 70

-PDGFβ

Question 71

Pericytes’ role in Alzheimer’s disease pathogenesis

Answer 71

AB plaques= disruption of BB -AB reduces cerebral blood flow via pericyte-mediated capillary constriction