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Cardio > Vascular Endothelium > Flashcards

Vascular Endothelium Flashcards

1
Q

What is the vascular system?

A

The vascular system is one of the largest and the most extensive networks in the body

Blood vessels are lined by endothelial cells.

When dysfunctional, the endothelium contributes to more diseases than any other organ

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2
Q

Describe the basic structure of blood vessels

A

Three layers:
(except for capillaries and venules)

Tunica adventitia
Vasa vasorum, nerves

Tunica media
Smooth muscle cells

Tunica intima
Endothelium

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3
Q

What happens in capillaries?

What are they formed by?

A

Capillaries is where the exchanges of nutrients and oxygen between blood and tissues occur
Capillaries and venules are formed by endothelium, supported by mural cells (pericytes) and a basement membrane

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4
Q

What are the different types of blood vessel heterogeneity

A

Vascular and endothelial

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5
Q

What do the majority of vessels in the body, microcirculation, consist of?

A

Endothelial cells surrounded by pericytes

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6
Q

What properties do endothelial cells and pericytes have?

A

Endothelial cells (and pericytes) have organotypic (tissue-specific) properties and unique gene/protein expression profiles

Continuous non fenestrated. fenestrated and discontinuous

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7
Q

Describe endothelial cells that line the vascular system

A

The Endothelium acts as a vital barrier separating blood from tissues
Very extensive: surface area > 1000 m2; weight >100 g
Endothelial cells are very flat, about 1-2 µm thick and 10-20 µm in diameter
Endothelial cells Form a monolayer, one cell deep (contact inhibition)
In vivo, endothelial cells live a long life and have a low proliferation rate (unless new vessels are required: angiogenesis)
Endothelial cell regulate essential functions of blood vessels

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8
Q

What functions of blood vessels and tissues does the endothelium control?

A

Vascular tone
Inflammation
Tissue homeostasis and regeneration
Permeability
Angiogenesis
Haemostasis & Thrombosis

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9
Q

What are angiocrine factors?

A

Angiocrine factors from endothelial cells are essential for the maintenance of tissue homeostasis and regeneration
The angiocrine profile of each tissue-specific microvascular endothelium is different; conversely, the tissue-specific microenvironment influences the phenotype of endothelial cells

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10
Q

What is the most abundant cell type in the normal myocardium?

A

Endothelial cells

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11
Q

What does single cell RNAseq do?

A

Single-cell RNA sequencingexamines thesequenceinformation from individualcellswith optimizednext-generation sequencingtechnologies.

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12
Q

What is sprouting angiogenesis

A

The formation of new vessels by sprouting from existing vessels

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13
Q

What is the physiology of sprouting angiogenesis?

A

Development
Menstrual cycle
Wound healing

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14
Q

What is the pathology of sprouting angiogenesis?

A

Cancer
Chronic inflammatory diseases
Atherosclerosis
Retinopathies
Ischemic diseases
Vascular malformations

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15
Q

What are the mechanisms of sprouting angiogenesis?***

A
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16
Q

In vivo models of angiogenesis*

A
17
Q

Describe the neovasculature for tumor angiogenesis?

A

Tumors less than 1 mm3 receive oxygen and nutrients by diffusion from host vasculature.

Larger tumors require new vessel network. Tumor secretes angiogenic factors that stimulate migration, proliferation, and neovessel formation by endothelial cells in adjacent established vessels.

Newly vascularized tumor no longer relies solely on diffusion from host vasculature, facilitating progressive growth.

18
Q

What is the angiogenic switch

A

The angiogenic switch is a discrete step in tumour development that can occur at different stages in the tumour-progression pathway, depending on the nature of the tumour and its microenvironment

19
Q

What are tumour blood vessels?

A

irregularly shaped, dilated, tortuous
not organized into definitive venules, arterioles and capillaries
leaky and haemorrhagic, partly due to the overproduction of VEGF
perivascular cells often become loosely associated

20
Q

How is the homeostatic balance maintained in endothelial cells?*

A

Angiogenesis
Inflammation
Thrombosis & haemostasis
Vascular Tone
Permeability

21
Q

Is healthy endothelium anti-thrombotic and anti-inflammatory

A

Yes

22
Q

What is thromboinflammation ?

When does it occur?

A

Loss of the normal antithrombotic and anti-inflammatory functions of endothelial cells causes thrombosis with associated inflammation

Occurs in many disorders, including sepsis, ischemia-reperfusion injury ….

23
Q

How is endothelial homeostasis maintained in resting endothelium?

A

Anti-inflammatory
Anti-thrombotic
Anti-proliferative

24
Q

How is endothelial homeostasis maintained in activated endothelium?

A

ATHEROSCLEROSIS

Viruses
Smoking
Thrombosis
Senescence
Mechanical stress
Inflammation
High blood pressure
OxLDL
High glucose
Permeability
Leukocyte recruitment

25
Q

Describe the pathogenesis of Atherosclerosis:
Response to injury model *

A
  1. Endothelial Dysfunction in Atherosclerosis
  2. Fatty-Streak Formation in Atherosclerosis
  3. Formation of an Advanced, Complicated Lesion of Atherosclerosis
26
Q

What are mechanisms for endothelial dysfunction in the pathogenesis of atherosclerosis

A

Leukocyte recruitment
Permeability
Shear stress
Angiogenesis

27
Q

Describe the leukocyte adhesion cascade*

Describe Leukocyte recruitment in venules vs arteries

A

Recruitment of blood leukocytes into tissues normally takes place during inflammation: leukocyte adhere to the endothelium of post-capillary venules and transmigrate into tissues

In atherosclerosis, leukocytes adhere to activated endothelium of large arteries and get stuck in the subendothelial space
Monocytes migrate into the subendothelial space, differentiate into macrophages and become foam cells

28
Q

Capillary vs post-capillary venule?

A

Capillary: endothelial cells surrounded by basement membrane and pericapillary cells (pericytes)
Post-capillary venule: structure similar to capillaries but more pericytes

29
Q

Describe Vascular permeability

A

The endothelium regulates the flux of fluids and molecules from blood to tissues and vice versa
Increased permeability results in leakage of plasma proteins through the junctions into the subendothelial space

30
Q

How does lipoprotein trapping and oxidative modification work?

A

Lipoprotiens
To lipoprotein oxidation
To Foam cell
To macrophage

31
Q

Why does atherosclerosis occur at branch points?

A

Atherosclerotic plaques occur preferentially at bifurcations and curvatures of the vascular tree

The flow patterns and hemodynamic forces are not uniform in the vascular system

32
Q

?What are the different effects on the endothelium of laminar and Disturbed Flow?

A

In straight parts of the arterial tree, blood flow is laminar and wall shear stress is high and directional

In branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress.

33
Q

What is the protective effect of laminar blood flow on the vascular endothelium?

A

Laminar blood flow promotes:
anti-thrombotic, anti-inflammatory factors
endothelial survival
Inhibition of SMC proliferation
Nitric oxide (NO) production

Disturbed blood flow promotes:
Thrombosis, inflammation (leukocyte adhesion)
endothelial apoptosis
SMC proliferation
Loss of Nitric oxide (NO) production

34
Q

What are the Multiple protective effects of nitric oxide (NO) on the vascular endothelium

A

NO is essential for the health of the cardiovascular system

Dilates blood vessels
Reduces platelet activation
Inhibits monocyte adhesion
Reduces proliferation of SMC in the vessel wall
Reduces release of superoxide radicals
Reduces oxidation of LDL cholesterol (major component of plaque)

35
Q

What does angiogenesis do?
What does therapeutic angiogenesis do?

A

Angiogenesis promotes plaque growth

Therapeutic angiogenesis prevents damage post-ischemia

36
Q

Summary of role of endothelium in atherosclerosis development?

A

Leukocyte recruitment
Leukocytes migrate into tissues through post-capillary venules during injury/inflammation
In atherosclerosis, endothelial activation in large arteries causes leukocyte migration into the subendothelial space, where they accumulate and contribute to plaque development

Blood flow
Blood flow affects the phenotype of the endothelium
Turbulent blood flow (often at branch points) causes chronic endothelial activation
Atherosclerosis is most often found at arterial branch points

Permeability
Permeability is tightly controlled by endothelial cell-cell junctions
Increased permeability to lipids contributes to early plaque formation

Angiogenesis
Angiogenesis is essential for development and physiological processes
Pathological angiogenesis is associated with advanced atherosclerotic plaques

Cardio (9 decks)

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