Samenvatting

Samenvatting colleges Cardiovascular Disease

6 keer verkocht

Instelling
Rijksuniversiteit Groningen (RuG)

Samenvatting van alle colleges van het 2e/3e jaars vak Cardiovascular Disease op de Rijksuniversiteit Groningen. Bevat de belangrijkste afbeeldingen uit de colleges. Voornamelijk steekwoorden en korte zinnen

[Meer zien]

Laatste update van het document: 3 jaar geleden

Voorbeeld 4 van de 34 pagina's

Bekijk voorbeeld

Geupload op 8 mei 2020
Bestand laatst geupdate op 13 april 2021
Aantal pagina's 34
Geschreven in 2019/2020
Type Samenvatting

Volgen

hannahkersbergen Lid sinds 9 jaar 50 documenten verkocht

€5,99

In winkelwagen

Op verlanglijstje

100% tevredenheidsgarantie
Direct beschikbaar na je betaling
Lees online óf als PDF
Geen vaste maandelijkse kosten

Cardiovascular Disease Summary

ENDOTHELIAL CELL FUNCTION → all CVDs contain some form of endothelial dysfunction

Cellular plasticity:
- heterogeneity of the vasculature: the
capillary network is different between organs
→ the blood supply is depended on the
metabolism of the tissue/organ
- organ-specific EC phenotypes
- endothelial-mesenchymal transition

Functional plasticity:
- barrier function (adhesion molecules):
1. Tight junctions (occludins): sealing of
the EC layer (membrane fusion)
2. Adherence junctions (VE-cadherin):
cell-cell connections (distribution of force), gap junctions (EC-EC communication (connection of
cytoplasm))
→ formation of gradients (pressure is high in vasculature, low in tissue, metabolites (active transport
from blood into tissues), inhibition of leukocyte migration
- immunology (leukocyte migration)
- thrombogenicity: heparan-sulfaphates (inhibition of thrombosis), secretion of coagulation factors
(PAI1/tPa/vWF), inhibition of platelet aggregation (NO/PGI2)
- vasomotor function (NO, ET1)
- vascularisation (vasculogenesis, angiogenesis)

VASCULAR SYSTEM

Function: transport of O2, nutrients, hormones and waste products
Vessel types: aorta → arteries → arterioles → capillaries → venules → veins → vena cava
Structure of vessels:

Tunica Externa Lamina Tunica Media Lamina Tunica Intima
(/Adventitia) elastica elastica
Cell type Fibroblasts externa Smooth muscle interna Endothelial cells
Matrix Collagens (ECM) Elastin fibers Basal membrane
(collagen I) (collagen III +
elastin)
Function Stiffness, Vasoconstriction Coagulation,
anchoring to or vasodilation transport,
tissue inflammation
Distribution of blood over smaller blood vessels → increases the cross-sectional area, flow rate ↓,
diffusion (gas exchange rate) ↑

Development of the vascular system (takes 6 weeks)
- day 12 post-fertilization: start
- first development of vasculature, then development of heart
- blood islands → extraembryonic vasculature (placenta, umbilical cord)
- mesoderm → embryonic vasculature
- 8 weeks post-fertilization: complete functional CV system

,Mesoderm formation  patterning: induced by cell-cell interaction
Blood vessel formation: BMP4 → mesoderm differentiation → FGF-2 → hemangioblast formation
→ (proliferation, FGF-2) → blood island
→ (differentiation) → angioblasts (blood vessel-forming cells), hematopoietic stem cells, mural cells
(pericytes/SMCs)

Vasculogenesis: formation of a primary vascular plexus in the embryo proper and extra-embryonic
tissues
- induced by VEGF/VEGFR signalling
- VEGF-A induces the formation of a capillary plexus
- mesoderm → hemangioblasts → tube formation → primary capillary plexus
- regulation is largely unknown
- mutations in VEGF/VEGFR/co-receptors → embryonic lethality ↑

Genes*
VEGF-A Vasculogenesis, angiogenesis
VEGF-B Embryonal angiogenesis
VEGF-C Lymph angiogenesis
VEGF-D
VEGF-E Viral-derived VEGF, function unknown
Receptors
VEGFR1 Angiogenesis (stalk cell differentiation)
VEGFR2 Vasculogenesis, angiogenesis (tip cell differentiation)
Co-receptors: NRP1 & NRP2: amplify VEGFR2 signalling
VEGFR3 Lymph angiogenesis
*VEGF-A(-E) isoforms: differences in heparin binding domain (binding to ECM) → presence
determines the diffusion capacity of VEGF (long versus short distance)

Arteriovenous differentiation
- starts before blood flow starts: important genetic component,
influenced/strengthened by circulation (mechanical forces)
- aorta & vena cava originate from the same primitive vessel
- ephrins (= ligand) → arteries
- ephs (= receptor) → veins
- bidirectional signalling
- cell-cell contact required, but results in repulsion
1. Arterial identity (active process)
- VEGF/VEGFR2 → EphB4 ↑
- Notch1 → EphrinB2↑, EphB4↓ (EphB4 expression is inhibited)
2. Venous identity (passive process)
- VEGF/VEGFR2 → EphB4 ↑
- segregation: active process (EphB4 signalling results in migration (away from aorta))

, Tip cell Stalk cell Phalanx EC
Location At the tip of the sprout Behind tip cell In blood vessel
Polarisation High; filopodia None None
Receptor expression VEGFR2-3, NRP1, DLL4 VEGFR1-2, Notch1/4 VEGFR1-2, Tie2
MMP expression Yes, MT1-MMP (col. IV) No No
Lumen None Developing Yes
Proliferation, rate No Yes, high Yes, low

Angiogenesis: formation of new blood vessels from existing ones
- some cells divide, some cells migrate

1. Tip cell
- VEGF binds to VEGFR2/3 → tip cell differentiation → expression of DII4 → DII4/Notch1 interaction
inhibits tip cell differentiation of adjacent cells by the inhibition of VEGFR2 expression
- filopodia/lamellopodia: high expression of VEGFR2 and integrins (sense gradients)
- VEGF/VEGFR2 → FAK activation → actin polymerization → movement
- MT1-MMP (MMP14): matrix metalloprotease that degrades the basal lamina (ECM) → allows
migration

2. Stalk cell
- DII4/Notch1 interaction inhibits VEGFR2/3 expression in stalk cells → decreased sensitivity to VEGF
- Notch1 → activates VEGFR1 (Flt1) expression → proliferation ↑
- Notch1 → activates integrin expression → cell-matrix interaction = stabilization
- Notch1 → activates Wnt signalling → cell-cell contacts ↑ (stabilization)
- pinocytosis (formation and endocytosis) of membrane intrusions → vacuole formation →
coalescence of vacuoles → intracellular lumen → fusion of intercellular lumens (ECs share 1 lumen,
but their cytoplasm remains separated)

3. Phalanx EC
- non-proliferating endothelium
- strong cell-cell adhesions of VE-Cadherin homodimers and Tie2-Ang1-Tie2 binding
- low VEGFR1/VEGFR2 expression (barely enough for cell survival)
- sVEGFR1: secreted decoy receptor for VEGF-A

Mural cells: form the tunica media and surround the endothelium
- SMCs: outside the basement membrane, multicellular layer
- pericytes: inside the basement membrane, single cells or single cell layer
- PDGF-BB: dimer that recruits mural cells (PDGFRβ), produced by tip cell, binds to the ECM
- Ang1 of mural cell activates Tie2 on EC → 1. PI3K-Akt → cell survival
2. NFκB inhibition → no inflammation
3. Rho kinase inhibition → EC-EC interactions are
stabilized with adherence junction (VE-Cadherin)
- S1P (mural cell) activates S1PR1 (EC) → activates Rac signalling → promotes EC-EC interactions (VE-
Cadherin) and EC-pericyte interactions (N-Cadherin)
- TGFβ (EC) activates TGFBR1(ALK5) (mural cell) → activates SMAD2/3 signalling → ECM production
(stabilization), SMC differentiation (contraction), inhibits mural cell proliferation (stabilization)

Lymph angiogenesis
- lymph vessels differentiate from the venous endothelium
- starts with blood clot (has no anti-thrombosis capacity)

, - lymph angiogenesis follows a program similar to sprouting angiogenesis, BUT
- VEGF-C (not VEGF-A) induces lymph angiogenesis
- VEGF-C signals via VEGFR3 (not VEGFR1)
- valves

ANGIOADAPTATION

- guarantee the supply of nutrients and oxygen, quick responses
- blood pressure → regulation of diffusion volume
- blood flow → regulation of diffusion time
- vascularization → regulation of diffusion capacity
- changes are made constant and are on demand
- remodelling to deal with metabolic demand, regulate blood flow to different organs, remove non-
function and excessive blood vessels

Arterial blood pressure is regulated autonomously (independent of blood flow and cardiac output)
- short term regulation: changes in volume distribution / cardiac output
- long term regulation: renin-angiotensin-aldosteron system (RAAS)

HIF1α signalling
- hypoxia induced → vasodilatation,
angiogenesis, oxygen transport capacity
→ increased blood flow (speed), flow
volume, increased transport capacity

Mechanotransduction: conversion of
mechanical signals to biochemical
signals → gene expression
- shear stress: increases during
increased blood flow
- normal stress: increases during
increased blood pressure
- no/limited blood flow = loss of shear stress → angiopoietine-2 activation → inhibits Tie2

Collateral formation: redistribution of flood flow by the arterialisation of a capillary or ateriole
- induced by a (massive) increase in shear stress
- can originate from newly-formed blood vessels (ischemia driven) or from pre-existing blood vessels
(flow driven)

Dit zijn jouw voordelen als je samenvattingen koopt bij Stuvia:

Bewezen kwaliteit door reviews

Studenten hebben al meer dan 850.000 samenvattingen beoordeeld. Zo weet jij zeker dat je de beste keuze maakt!

In een paar klikken geregeld

Geen gedoe — betaal gewoon eenmalig met iDeal, creditcard of je Stuvia-tegoed en je bent klaar. Geen abonnement nodig.

Direct to-the-point

Studenten maken samenvattingen voor studenten. Dat betekent: actuele inhoud waar jij écht wat aan hebt. Geen overbodige details!

Veelgestelde vragen

Wat krijg ik als ik dit document koop?

Je krijgt een PDF, die direct beschikbaar is na je aankoop. Het gekochte document is altijd, overal en oneindig toegankelijk via je profiel.

Tevredenheidsgarantie: hoe werkt dat?

Onze tevredenheidsgarantie zorgt ervoor dat je altijd een studiedocument vindt dat goed bij je past. Je vult een formulier in en onze klantenservice regelt de rest.

Van wie koop ik deze samenvatting?

Stuvia is een marktplaats, je koop dit document dus niet van ons, maar van verkoper hannahkersbergen. Stuvia faciliteert de betaling aan de verkoper.

Zit ik meteen vast aan een abonnement?

Nee, je koopt alleen deze samenvatting voor €5,99. Je zit daarna nergens aan vast.

Is Stuvia te vertrouwen?

4,6 sterren op Google & Trustpilot (+1000 reviews)

Afgelopen 30 dagen zijn er 68175 samenvattingen verkocht

Opgericht in 2010, al 15 jaar dé plek om samenvattingen te kopen

Begin nu gratis

Samenvatting

Samenvatting colleges Cardiovascular Disease

Document informatie

Onderwerpen

Geschreven voor

Verkoper

Ontvangen beoordelingen

Voorbeeld van de inhoud