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CELL 302 > Lecture C3 + C4 > Flashcards

Lecture C3 + C4 Flashcards

1
Q

cardiovascular system over time

A

-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)

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2
Q

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

A

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

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3
Q

In 1973, Eric Jaffe and colleagues did what?

A

isolated and cultured endothelial cells in vitro

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4
Q

endothelial cells are cells that ____

A

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

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5
Q

Ontogeny (def.)

A

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

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6
Q

Blood islands give rise to both ______

A

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

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7
Q

Formation of endothelial cells

A

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

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8
Q

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

A

Vasculogenesis and angiogenesis

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9
Q

endothelial precursor cells aka _____

A

angioblasts

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10
Q

Vasculogenesis (def.)

A

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

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11
Q

Angiogenesis (def.)

A

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

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12
Q

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 _____

A

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

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13
Q

Smooth muscle/pericyte differentiation during vasculogenesis requires ____

A

TGF-B activation

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14
Q

_____ is endothelial cell marker

A

Tie2

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15
Q

angiogenesis: how sprouting happens?

A

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

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16
Q

angiogenesis: how intussusception happens?

A

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

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17
Q

How can you study endothelial cells

A

-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

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18
Q

Weibel-Palade bodies (WPBs) are what?

A

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

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19
Q

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

A

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

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20
Q

hemostasis (def.)

A

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

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21
Q

WBPs contains this that determines its cigar shape?

A

von Willebrand Factor (VWF); multimerized hemostatic protein

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22
Q

VWF function

A

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

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23
Q

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 ______

A

-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

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24
Q

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

A

-vWF tubulation
-right-handed coil

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25
Q

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

A

cleaved

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26
Q

cardiac muscle descr.

A

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

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27
Q

smooth muscle descr.

A

-lacks striations
-have slow, involuntary contractions

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28
Q

skeletal muscle has no ____

A

intercalated discs

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29
Q

skeletal vs. cardiac: gap junctions

A

-no
-yes

30
Q

skeletal vs. cardiac: contraction regulation

A

-voluntary
-involuntary

31
Q

skeletal vs. cardiac: source of Ca++

A

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

32
Q

skeletal vs. cardiac: pacemaker

A

-no
-yes

33
Q

skeletal vs. cardiac: electrical stimulation

A

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

34
Q

PM of muscle cell

A

sacrolemma

35
Q

cardiomyocytes descr.

A
  • 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)
36
Q

Junctional complexes of cardiomyocytes do what?

A

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

37
Q

The intercalated disc controls ______ of the cardiac tissue

A

electrical and mechanical coupling

38
Q

Junctional complexes contain: ______ + functions

A

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

39
Q

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

A

-DSMs and AJs
-area composita

40
Q

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

A

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

41
Q

Gap junctions do what?

A

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

42
Q

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

A

-Connexins
-connexon

43
Q

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

A

-proper propagation of the electrical impulse
-sequential and coordinated

44
Q

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

A

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

45
Q

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

A

-sinoatrial (SA)
-80 action potentials

46
Q

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

A

-gap junctions
-functional syncytium

47
Q

Transverse-tubules (T tubules) are ______

A

specialized sarcolemma invaginations

48
Q

Cardiac SR membranes are specialized ER domains for the _______

A

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

49
Q

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

A

the longitudinal SR and the junctional SR

50
Q

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

A

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

51
Q

Ryanodine + Ryanodine receptor

A

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

52
Q

Excitation-contraction coupling of cardiac muscle cells

A
  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.
53
Q

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

A

-involuntary contractions
-slow and of greater duration

54
Q

Smooth muscle cells (descr.)

A

-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

55
Q

contractions of smooth muscle cells shown by _____

A

dense bodies getting closer

56
Q

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.

A

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

57
Q

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

A

thickens and hypertrophied in bronchiole

58
Q

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

A

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

59
Q

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 _____.

A

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

60
Q

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

A

-pericytes
-vascular smooth muscles
-poorly defined cell type

61
Q

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 ______.

A

-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

62
Q

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

A

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

63
Q

Continuous capillaries are normally associated with perivascular contractile cells called_____

A

-pericytes

64
Q

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

A

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

65
Q

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

A

peg-socket contacts and adhesion plaques

66
Q

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

A

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

67
Q

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 _______

A

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

68
Q

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

A

-pericytes

69
Q

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

A

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

70
Q

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

A

-PDGFβ

71
Q

Pericytes’ role in Alzheimer’s disease pathogenesis

A

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

CELL 302 (18 decks)

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