25 Questions
What is the primary factor that determines microvascular permeability?
Barrier properties of the endothelium
Which of the following agents is NOT a pro-inflammatory mediator that increases microvascular permeability?
Nitric oxide
What is the primary function of quiescent endothelial cells in the vascular wall?
To provide a barrier to solutes and regulate nutrient transport
What is the term for the formation of new blood vessels from existing ones?
Angiogenesis
Which of the following is a key regulator of vascular barrier function and inflammation?
Endothelial nitric oxide synthase (eNOS)
What is the primary function of the endothelial cell barrier in capillaries?
To provide a selectively permeable barrier between blood and tissues
What is the process by which endothelial cells form new blood vessels in response to tissue injury or increased oxygen demand?
Sprouting angiogenesis
What is the primary role of nitric oxide in endothelial function?
To control the contraction of vascular smooth muscle cells
What is the mechanism by which endothelial cells regulate the movement of substances and leukocytes across the endothelial barrier?
Transcellular and paracellular transport
What is the enzyme responsible for producing nitric oxide in endothelial cells?
Endothelial nitric oxide synthase (eNOS)
What is the primary function of SERCA in the context of myosin light chain dephosphorylation?
Calcium pumping back into the SR
What is the result of endothelial NO production in resistance vessels?
Reducing myosin light chain phosphorylation
What is the role of p27kip1 in the context of Rho/ROCK signaling in arteriosclerosis?
Inhibition of VSMC proliferation
What is the endothelium responsible for lining in the body?
The lumen of all blood vessels and the surfaces of the heart chambers
What is the approximate mass of the endothelium in an adult human body?
1 kg
What is the primary mechanism of neovessel formation in response to ischemic tissues?
Sprouting angiogenesis driven by local endothelial cells
What is the main consequence of diminished angiogenesis in diabetic patients?
Increased risk of limb amputation
Which of the following signaling pathways is involved in the regulation of lymphangiogenesis?
VEGF-VEGFRs
What is the effect of VEGF-A on vascular permeability?
Increases vascular permeability
What is the primary function of endothelial cells in response to ischemic tissues?
To dedifferentiate and migrate to form new vessels
What is the primary cause of death in developed countries?
Dysfunction of blood vessels
What is the main function of blood vessels in the body?
To establish a delivery and exchange system for oxygen and nutrients to tissues
What is the role of vascular endothelial cells in the vascular wall?
To regulate vascular integrity
What is the significance of understanding molecular and cellular mechanisms of blood vessel function?
To improve public health and develop therapeutics
What is the importance of vascular health?
It is vital for public health and therapeutics development
Study Notes
Microvascular Permeability
- Microvascular permeability is determined by the barrier properties of the endothelium
- The lowest permeability is found in the brain (blood-brain barrier)
- The highest permeability is found in the liver (sinusoids)
Agents that Increase Microvascular Permeability
- Pro-inflammatory mediators, such as bradykinin, histamine, platelet-activating factor, and vascular endothelial growth factor
- These agents act on post-capillary venules and control permeability
eNOS Trafficking and Localized NO Signaling
- Regulates vascular barrier function and controls inflammation
- eNOS trafficking is essential for localized NO signaling and vascular barrier function
Endothelial Cells (ECs)
- Drive the formation of new blood vessels from existing ones
- EC functions can be broadly classified into two types of activities:
- Quiescent ECs line the vascular wall and provide a barrier to solutes, regulate nutrient transport, and maintain bloodstream homeostasis
- Proliferative/migratory ECs form new blood vessels (sprouting angiogenesis)
Vascular Endothelial Cells (ECs)
- Provide a selectively permeable barrier between the blood and tissues
- Substances and leukocytes in circulation move in and out in a regulated manner across the EC barrier
- Achieved by transcellular (transporter) and paracellular (cell-cell junctions, EC contraction) mechanisms
Nitric Oxide (NO)
- Is the central regulator of endothelial and vascular homeostasis
- Relaxes VSMCs and dilates blood vessels to control blood flow and blood pressure
- Prevents platelets from sticking to vessel walls (anti-coagulation)
- Regulates (suppresses) inflammation by controlling the expression of adhesion molecules
Angiogenesis
- Is a complex process driven by ECs
- Two modalities of neovessel formation:
- Sprouting angiogenesis (~75%): driven by local ECs
- Vasculogenesis (~25%): driven by endothelial progenitor cells from the bone marrow
Diabetic Foot and Angiogenesis
- Diabetic foot suffers impaired collateralization due to diminished angiogenesis and vasculogenesis
- Critical limb ischemia (CLI) occurs when blood flow to limbs is reduced or interrupted for a long period
- Leading cause of limb amputation (1 leg / 30 sec) with a poor prognosis (5-yr survival 32%)
Vascular Endothelial Growth Factors (VEGFs) and Their Receptors
- Are key mediators of angiogenesis
- VEGFs and VEGFRs regulate both vasculogenesis and angiogenesis
- VEGF-A stimulates angiogenesis, strongly increases vascular permeability, and stimulates cell migration in endothelial and myeloid cells
Test your knowledge on the structure and function of endothelial cells, their role in forming blood vessel walls, and their selective permeability in regulating the movement of substances and leukocytes. Explore how quiescent EC monolayer facilitates the exchange between blood and tissues.
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