Lecture C3 + C4 Flashcards
cardiovascular system over time
-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)
_____ coined the name ‘endothelia’ for epithelia that arise from the ______, and which come to line ______
-Wilhelm His (1831–1904)
-mesoderm
-body cavities, and the blood and lymphatic vessel
In 1973, Eric Jaffe and colleagues did what?
isolated and cultured endothelial cells in vitro
endothelial cells are cells that ____
line the internal surface of all components of the blood and lymphatic systems
Ontogeny (def.)
the origination and development of an organism, usually from the time of fertilization of the egg to adult
Blood islands give rise to both ______
vasculogenesis (process of blood vessel formation) and primitive hematopoiesis (production of all blood cells)
Formation of endothelial cells
-mesodermal cells form blood islands (hemangioblasts)
-Hemangioblasts form endothelial and hematopoietic (primitive HSC) lineages
_________ are the fundamental processes by which new blood vessels are formed.
Vasculogenesis and angiogenesis
endothelial precursor cells aka _____
angioblasts
Vasculogenesis (def.)
differentiation of endothelial precursor cells, or angioblasts, into endothelial cells and the de novo formation of a primitive vascular
network.
Angiogenesis (def.)
growth of new capillaries from preexisting blood vessels either via sprouting (sprout off existing vessel) or intussusception (splitting existing blood vessel into two)
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 _____
-VEGF signals
-Flk1, Flt1
-pericytes and smooth muscle
-several ligands and receptor interaction
Smooth muscle/pericyte differentiation during vasculogenesis requires ____
TGF-B activation
_____ is endothelial cell marker
Tie2
angiogenesis: how sprouting happens?
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
angiogenesis: how intussusception happens?
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
How can you study endothelial cells
-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
Weibel-Palade bodies (WPBs) are what?
-large (1-6 μm long) cigarshaped secretory organelles used for post-synthesis storage in endothelial cells.
WPB can be triggered to ____. They store factors that are essential to _____
-release their contents rapidly
-hemostasis, inflammation, regulate vascularity tonicity and angiogenesis
hemostasis (def.)
-process to prevent and stop bleeding, first step in wound healing
WBPs contains this that determines its cigar shape?
von Willebrand Factor (VWF); multimerized hemostatic protein
VWF function
-adhere platelets to damaged endothelium
-allows for platelet aggregation, clot is stabilized by fibrin strands around platelet plug
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 ______
-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
vWF at the golgi, calcium and low pH promote ______. Dimers are stacked into _____
-vWF tubulation
-right-handed coil
WBP is exocytosed and vWF is _____ in the event of injury to blood vessel
cleaved
cardiac muscle descr.
-has cross-striations and is composed of elongated, branched cells bound to one another at intercalated discs=junctions
-Contraction is involuntary, vigorous, and rhythmic
smooth muscle descr.
-lacks striations
-have slow, involuntary contractions
skeletal muscle has no ____
intercalated discs
skeletal vs. cardiac: gap junctions
-no
-yes
skeletal vs. cardiac: contraction regulation
-voluntary
-involuntary
skeletal vs. cardiac: source of Ca++
-sarcoplasmic reticulum (ER)
-sarcoplasmic reticulum and extracellular fluid
skeletal vs. cardiac: pacemaker
-no
-yes
skeletal vs. cardiac: electrical stimulation
-nervous system (excitation)
-pacemaker (excitation); nervous system (beating frequency modulation)
PM of muscle cell
sacrolemma
cardiomyocytes descr.
- 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)
Junctional complexes of cardiomyocytes do what?
-promote rapid impulse conduction through many cells simultaneously and contraction of many adjacent cells as a unit
The intercalated disc controls ______ of the cardiac tissue
electrical and mechanical coupling
Junctional complexes contain: ______ + functions
-Desmosomes: adhesion
-gap junctions- excitability
-adherens junctions (fascia adherens)- adhesion
In epithelia, ______ are distinct, whereas in vertebrate hearts, these junctions can become intermixed in a structure called the _____
-DSMs and AJs
-area composita
In the area composita, ____ is substituted by ______ in adherens junctions and the _____ interacts with _____
-catenin-β1
-plakoglobin (PG)
-plakophilin (PKP2)
-catenin-α3 (αT)
Gap junctions do what?
enable passive diffusion of metabolites, water and ions between cells (electrical and metabolic communication between cells)
Gap junctions:______, assembled to form a pore, called the______
-Connexins
-connexon
In cardiac muscle gap junctions ensure a ______ which triggers _____ contraction of the cardiomyocytes
-proper propagation of the electrical impulse
-sequential and coordinated
At resting state, the cells are _____ on the inside and _____ on the outside. During an action potential _____ ions flow in, and ____ ions flow out.
-more negative (K+ inside)
-positive (Na+/Ca++ outside)
-Ca++ and Na+
-K+
The pacemaker cells of the _____ node fire spontaneously (~______/min).
-sinoatrial (SA)
-80 action potentials
Rapid communication of action potentials between pacemaker
cells and contractile muscle cells happens through ______. This allows cardiac muscle fibers to work together as a _____.
-gap junctions
-functional syncytium
Transverse-tubules (T tubules) are ______
specialized sarcolemma invaginations
Cardiac SR membranes are specialized ER domains for the _______
regulation of Ca2+ transport and control of excitation–contraction coupling
The SR can be divided into at least two structural and functional domains: ______
the longitudinal SR and the junctional SR
_______ are mostly concentrated in the junctional SR, where they have an important role in ______. Longitudinal SR is mainly composed of _______.
-Ryanodine receptors (RyR) and Ca2+ channels, and calsequestrin
-Ca2+ storage and Ca2+ release to trigger muscle contraction
-SERCA (sarco/endoplasmic reticulum Ca2+-ATPase)
Ryanodine + Ryanodine receptor
-plant extract that is a pesticide/toxic to humans too
-blocks ryanodine receptor-> block contractions -> causes paralysis
Excitation-contraction coupling of cardiac muscle cells
- Action potentials traveling along the sarcolemma and down into the T-tubule system depolarize the cell membrane.
- L-type calcium channels open to permit calcium entry into the cell.
- Calcium influx triggers calcium release from the SR through calcium-release channels (ryanodine receptors). This is called calcium-induced calcium release.
- 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.
- 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.
Smooth muscle is responsible for _____ in various tissues. These contractions are relatively _____ than in skeletal or cardiac muscle
-involuntary contractions
-slow and of greater duration
Smooth muscle cells (descr.)
-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
contractions of smooth muscle cells shown by _____
dense bodies getting closer
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.
-nerve or hormonal
-Calmodulin
-calcium-Calmodulin
-MLCK (myosin light chain kinase)
-myosin light-chain phosphorylation
-conformational change
-filaments
-MLCK
Smooth muscle pathophysiology in asthma: Airway smooth muscle cells (ASM) do what?
thickens and hypertrophied in bronchiole
Activation of the airway epithelium by allergens causes the _____. This leads to the recruitment of ______
-release of growth factors from epithelial cells
-inflammatory cells which release cytokines
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 _____.
-myofibroblast migration
-proliferation
-hypertrophy
-ECM components
-soluble mediators
-ASM mass
Mural cells include vessel-associated cell types such as_____ and _______. Pericytes remain a relatively _____, without highly specific markers available for their identification.
-pericytes
-vascular smooth muscles
-poorly defined cell type
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 ______.
-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
vSMCs covering venules have a ________, which, unlike arteriolar vSMCs, do not wrap ______
-relatively big, stellate shape cell body with many branching processes
-circularly around the endothelium
Continuous capillaries are normally associated with perivascular contractile cells called_____
-pericytes
Pericytes: They have _______ that partly surround the endothelial layer. They secrete many _____ and form their own ____, which fuses with the basement membrane of the ____
-long cytoplasmic processes
-ECM components
-basal lamina
-endothelial cells
Despite being separated by the shared basement membrane, pericytes and endothelial cells make numerous direct contacts of different type: ______
peg-socket contacts and adhesion plaques
Peg-socket contacts: _______ (pegs) are inserted into ________ (pockets). The peg-socket contacts contain cell-to-cell junction proteins, such as ______
-pericyte cell membrane protrusion-like structures
-endothelial cell membrane invaginations
-N-cadherin and CX43 hemichannels (gap junctions)
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 _______
-the blood-brain barrier (BBB)
-passive transport of cells, proteins, and bioactive compounds present in the blood
Within the CNS, ____ are important for maintaining the endothelial blood-brain barrier (BBB).
-pericytes
Pericytes are integral members of the _____ (NVU). Pericytes promote tight and adherens junction formation via control of endothelial cell expression of _______(between endothelial cells).
-neural vascular unit
-occludin and claudin-5 and VE- cadherin
The recruitment of pericytes to the NVU can be mediated by ____
secreted by endothelial cells
-PDGFβ
Pericytes’ role in Alzheimer’s disease pathogenesis
AB plaques= disruption of BB
-AB reduces cerebral blood flow via pericyte-mediated capillary constriction
