Module 2 Vascular Smooth Muscle Cells) Flashcards
Q1: Where are vascular smooth muscle cells (VSMCs) found and what is their main function?
✅ Answer:
VSMCs are located in the tunica media of blood vessels. Their primary function is to regulate vascular tone, blood pressure, and pulse propagation through coordinated contraction.
Q2: What is the arrangement and cytoskeletal feature that enables VSMC contraction?
✅ Answer:
VSMCs are arranged circumferentially in concentric layers. They contain dense bodies and an actin cytoskeleton, which facilitates coordinated contraction. Gap junctions allow electrical and chemical coupling between cells.
❓Q3: Compare endothelial cell (EC) and smooth muscle cell orientation and interaction in vessels.
✅ Answer:
ECs align with the flow and act as a semipermeable barrier.
VSMCs wrap around the vessel and provide contractile force.
ECs and VSMCs communicate via gap junctions, ion channels, and signaling receptors.
Q4: How does the ECM contribute to SMC function and remodelling?
✅ Answer:
ECM binds integrins like α1β1 (collagen IV) and α7β1 (laminin) for anchorage.
ECM sequesters TGF-β, which is released upon damage and triggers repair/remodelling.
Q5: Which two growth factors are central to EC–VSMC crosstalk and what are their roles?
✅ Answer:
TGF-β: Involved in both repair and pro-remodelling, bidirectional signaling.
PDGF-B: Drives VSMC dedifferentiation and migration, especially when NO is low.
Q6: Define VSMC phenotype switching.
✅ Answer: A reversible change where contractile VSMCs dedifferentiate into a mesenchymal-like state, then differentiate into other phenotypes (e.g., fibroblast-, macrophage-, osteogenic-like) based on stimuli.
Q7: What is the role of KLF4 in phenotype switching?
✅ Answer: KLF4 is a transcription factor expressed in the mesenchymal-like state. It drives the loss of contractile gene expression and enables plasticity toward other cell types.
Q8: Name four synthetic phenotypes of VSMCs and a function of each.
✅ Answer:
Fibroblast-like – ECM production and repair
Macrophage-like – Engulfing lipids in atherosclerosis
Osteogenic-like – Deposit calcium, cause vessel stiffening
Adipocyte-like – Fat storage/metabolism (less understood)
Q9: How does VSMC plasticity contribute to atherosclerosis?
✅ Answer: Upon endothelial damage and lipid accumulation, VSMCs:
Migrate into the intima
Dedifferentiate into macrophage-like cells (lipid uptake)
Or fibroblast-like (collagen deposition)
Contributing to plaque growth and calcification
Q10: What experimental evidence supports oligoclonal expansion in VSMCs?
✅ Answer: Lineage tracing using multicolor reporters shows that clusters of cells in plaques often share the same label → indicating they derive from a single VSMC precursor, not from many (oligoclonal, not polyclonal).
Q11: What is the role of SCA1-positive VSMCs?
✅ Answer: SCA1 marks a progenitor-like subset of VSMCs primed for phenotype switching. They contribute to remodelling and disease states, such as atherosclerosis.
Q12: Name two vascular diseases where VSMC switching contributes and how.
✅ Answer:
Aortic aneurysm – Loss of contractile VSMCs and ECM degradation leads to wall thinning.
Hypertension – Abnormal calcium signaling and remodeling due to phenotype changes increase stiffness.
Describe the steps involved in VSMC switching from a contractile to macrophage-like phenotype in atherosclerosis.
✅ Model Answer:
Endothelial damage reduces NO, increasing PDGF.
VSMCs dedifferentiate into mesenchymal-like cells (expressing KLF4).
Under cholesterol/inflammatory signals, they become macrophage-like, expressing phagocytic markers and contributing to plaque development.
How can VSMC plasticity be beneficial and harmful?
✅ Model Answer:
Beneficial: Repairs vessel damage, promotes angiogenesis.
Harmful: In disease, excessive switching leads to plaque formation, calcification, and loss of contractile function.
