Pathophysiology of atherosclerosis MCQs With Answer

The pathophysiology of atherosclerosis is central to understanding cardiovascular disease for B. Pharm students. This concise overview links endothelial dysfunction, lipid oxidation, foam cell formation, chronic inflammation, smooth muscle migration, and plaque destabilization to clinical outcomes. Key concepts include low-density lipoprotein (LDL) retention and oxidation, macrophage scavenger receptors, cytokine-driven matrix degradation, and the role of high-density lipoprotein (HDL) in reverse cholesterol transport. Grasping molecular mediators like VCAM-1, MMPs, and NLRP3 inflammasome enhances therapeutic reasoning for statins, PCSK9 inhibitors, and anti-inflammatory strategies. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which early event is most critical in the initiation of atherosclerotic plaque formation?

• Vascular smooth muscle cell calcification
• Endothelial dysfunction
• Thrombus organization
• Fibrous cap rupture

Correct Answer: Endothelial dysfunction

Q2. Oxidized LDL (oxLDL) contributes to atherogenesis primarily by:

• Enhancing HDL-mediated cholesterol efflux
• Stimulating foam cell formation via scavenger receptors
• Inhibiting endothelial adhesion molecule expression
• Decreasing inflammatory cytokine release

Correct Answer: Stimulating foam cell formation via scavenger receptors

Q3. Which macrophage receptor is most associated with uptake of modified LDL leading to foam cell formation?

• LDL receptor (LDLR)
• Scavenger receptor class A (SR-A)
• Insulin receptor
• Transferrin receptor

Correct Answer: Scavenger receptor class A (SR-A)

Q4. The fatty streak in early atherosclerosis is primarily composed of:

• Lymphocytes and calcified matrix
• Smooth muscle cells and collagen
• Foam cells and lipid-laden macrophages
• Platelet-rich thrombus

Correct Answer: Foam cells and lipid-laden macrophages

Q5. Which adhesion molecule is upregulated on activated endothelium and promotes monocyte recruitment?

• Albumin
• VCAM-1
• Hemoglobin
• Fibrillin

Correct Answer: VCAM-1

Q6. Matrix metalloproteinases (MMPs) promote plaque vulnerability by:

• Enhancing collagen synthesis in fibrous cap
• Degrading extracellular matrix proteins in the fibrous cap
• Preventing smooth muscle cell migration
• Increasing HDL production

Correct Answer: Degrading extracellular matrix proteins in the fibrous cap

Q7. Which cytokine is a key pro-inflammatory mediator in atherosclerotic plaques?

• Interleukin-10 (IL-10)
• Tumor necrosis factor-alpha (TNF-α)
• Transforming growth factor-beta (TGF-β)
• Interferon-beta (IFN-β)

Correct Answer: Tumor necrosis factor-alpha (TNF-α)

Q8. High-density lipoprotein (HDL) is protective because it:

• Enhances LDL oxidation
• Promotes reverse cholesterol transport from macrophages
• Stimulates foam cell formation
• Increases endothelial adhesion molecule expression

Correct Answer: Promotes reverse cholesterol transport from macrophages

Q9. Which enzyme is rate-limiting for cholesterol synthesis and target of statin therapy?

• HMG-CoA reductase
• Acetyl-CoA carboxylase
• Lipoprotein lipase
• Cholesterol ester transfer protein (CETP)

Correct Answer: HMG-CoA reductase

Q10. Which lipoprotein is most atherogenic due to its propensity to infiltrate the arterial intima?

• High-density lipoprotein (HDL)
• Very-low-density lipoprotein (VLDL)
• Low-density lipoprotein (LDL)
• Chylomicrons

Correct Answer: Low-density lipoprotein (LDL)

Q11. Endothelial nitric oxide (NO) protects against atherosclerosis by:

• Promoting platelet aggregation
• Causing vasoconstriction
• Inhibiting leukocyte adhesion and smooth muscle proliferation
• Increasing LDL oxidation

Correct Answer: Inhibiting leukocyte adhesion and smooth muscle proliferation

Q12. Which cell type synthesizes extracellular matrix components and contributes to fibrous cap formation?

• Neutrophils
• Vascular smooth muscle cells (VSMCs)
• Red blood cells
• Endothelial progenitor cells

Correct Answer: Vascular smooth muscle cells (VSMCs)

Q13. Plaque rupture commonly leads to which immediate pathological event?

• Resolution of inflammation
• Thrombus formation and acute vessel occlusion
• Increased HDL levels
• Enhanced collagen deposition

Correct Answer: Thrombus formation and acute vessel occlusion

Q14. Which laboratory marker is most commonly used as a systemic marker of vascular inflammation associated with atherosclerosis?

• Creatine kinase-MB
• C-reactive protein (CRP)
• Albumin
• Hemoglobin A1c

Correct Answer: C-reactive protein (CRP)

Q15. Foam cell apoptosis and defective efferocytosis contribute to:

• Fibrous cap thickening
• Necrotic core formation
• Increased HDL-mediated cholesterol efflux
• Decreased plaque lipid content

Correct Answer: Necrotic core formation

Q16. Which of the following best describes the role of reactive oxygen species (ROS) in atherosclerosis?

• ROS reduce LDL oxidation and are anti-atherogenic
• ROS mediate LDL oxidation and endothelial dysfunction
• ROS synthesize nitric oxide in endothelial cells
• ROS exclusively originate from dietary sources

Correct Answer: ROS mediate LDL oxidation and endothelial dysfunction

Q17. The NLRP3 inflammasome in macrophages promotes atherogenesis by activating which cytokine?

• Interleukin-1β (IL-1β)
• Interleukin-4 (IL-4)
• Interleukin-2 (IL-2)
• Interleukin-10 (IL-10)

Correct Answer: Interleukin-1β (IL-1β)

Q18. Which genetic animal model is widely used to study atherosclerosis due to hypercholesterolemia?

• Nude mice
• ApoE knockout mice
• SCID mice
• Transgenic pigs overexpressing HDL

Correct Answer: ApoE knockout mice

Q19. Which process explains smooth muscle cell migration into the intima during plaque development?

• Transdifferentiation from endothelial cells via endothelial-to-mesenchymal transition (EndMT)
• Chemokine- and growth factor-driven migration from media to intima
• Direct differentiation from circulating platelets
• Apoptosis of adventitial fibroblasts

Correct Answer: Chemokine- and growth factor-driven migration from media to intima

Q20. Lipoprotein(a) contributes to atherosclerosis risk primarily because it:

• Enhances HDL function
• Competes with LDL for receptor-mediated uptake
• Contains apolipoprotein(a) that promotes thrombosis and inflammation
• Directly degrades collagen in the fibrous cap

Correct Answer: Contains apolipoprotein(a) that promotes thrombosis and inflammation

Q21. Which imaging modality is most useful for identifying calcified atherosclerotic plaques in coronary arteries?

• Electrocardiography (ECG)
• Coronary artery calcium scoring by CT
• Carotid Doppler ultrasound
• Plain chest X-ray

Correct Answer: Coronary artery calcium scoring by CT

Q22. Which therapeutic strategy directly reduces LDL particle number by targeting PCSK9?

• Statins
• PCSK9 monoclonal antibodies
• Fibrates
• Niacin

Correct Answer: PCSK9 monoclonal antibodies

Q23. Ezetimibe reduces atherosclerotic risk primarily by:

• Inhibiting intestinal cholesterol absorption
• Increasing HMG-CoA reductase activity
• Blocking HDL uptake in the liver
• Stimulating LDL receptor degradation

Correct Answer: Inhibiting intestinal cholesterol absorption

Q24. Intraplaque hemorrhage contributes to plaque progression by:

• Reducing lipid core size
• Introducing erythrocyte membranes and extra cholesterol into the plaque
• Stabilizing the fibrous cap
• Decreasing macrophage recruitment

Correct Answer: Introducing erythrocyte membranes and extra cholesterol into the plaque

Q25. Which histological stain is commonly used to identify lipids in frozen tissue sections of atherosclerotic lesions?

• Hematoxylin and eosin (H&E)
• Oil Red O
• Masson’s trichrome
• Silver stain

Correct Answer: Oil Red O

Q26. Chronic hyperglycemia in diabetes accelerates atherosclerosis mainly through:

• Enhanced HDL production
• Glycation of proteins, increased oxidative stress, and endothelial dysfunction
• Decreasing LDL oxidation
• Reducing inflammatory cytokines

Correct Answer: Glycation of proteins, increased oxidative stress, and endothelial dysfunction

Q27. Which cellular event is most responsible for forming the necrotic core of advanced plaques?

• Proliferation of endothelial cells
• Accumulation of apoptotic/necrotic foam cells and extracellular lipid
• Increased collagen deposition
• HDL-mediated cholesterol efflux

Correct Answer: Accumulation of apoptotic/necrotic foam cells and extracellular lipid

Q28. Shear stress patterns that predispose to atherosclerosis are typically:

• High laminar shear stress
• Low and oscillatory shear stress
• Uniform shear stress
• Absent shear stress only in veins

Correct Answer: Low and oscillatory shear stress

Q29. Which of the following best explains how statins exert anti-inflammatory effects beyond lipid lowering?

• By increasing LDL oxidation
• By inhibiting isoprenoid synthesis affecting immune cell signaling
• By directly binding to VCAM-1
• By blocking MMP gene transcription through direct DNA binding

Correct Answer: By inhibiting isoprenoid synthesis affecting immune cell signaling

Q30. Which component of the plaque is most directly associated with risk of acute thrombosis when disrupted?

• Calcified nodule
• Fibrous cap exposing thrombogenic necrotic core
• Intact endothelium
• Adventitial adipose tissue

Correct Answer: Fibrous cap exposing thrombogenic necrotic core

Q31. Which growth factor is important for VSMC proliferation and migration in plaques?

• Erythropoietin (EPO)
• Platelet-derived growth factor (PDGF)
• Insulin-like growth factor binding protein (IGFBP)
• Vascular endothelial growth inhibitor (VEGI)

Correct Answer: Platelet-derived growth factor (PDGF)

Q32. What is the primary role of cholesterol ester transfer protein (CETP) in lipoprotein metabolism relevant to atherosclerosis?

• Transferring cholesteryl esters from HDL to LDL/VLDL in exchange for triglycerides
• Hydrolyzing triglycerides in chylomicrons
• Synthesizing apolipoprotein A-I
• Transporting free fatty acids into mitochondria

Correct Answer: Transferring cholesteryl esters from HDL to LDL/VLDL in exchange for triglycerides

Q33. Which of the following is a common consequence of advanced atherosclerotic narrowing in coronary arteries?

• Pulmonary embolism
• Myocardial ischemia and infarction
• Nephrotic syndrome
• Portal hypertension

Correct Answer: Myocardial ischemia and infarction

Q34. Which cell type within a plaque releases tissue factor that promotes coagulation after plaque disruption?

• Endothelial cells exclusively
• Macrophages and smooth muscle cells
• Red blood cells
• Lymphocytes exclusively

Correct Answer: Macrophages and smooth muscle cells

Q35. Which pharmacologic class primarily lowers triglycerides and may influence atherosclerotic risk?

• Statins
• Fibrates
• Beta-blockers
• ACE inhibitors

Correct Answer: Fibrates

Q36. Which experimental finding supports the role of inflammation in atherosclerosis?

• Anti-inflammatory therapy with IL-1β inhibitors reduced cardiovascular events in trials
• Complete absence of macrophages in plaques
• Decreased cytokine levels in symptomatic patients
• Removal of HDL increases plaque stability

Correct Answer: Anti-inflammatory therapy with IL-1β inhibitors reduced cardiovascular events in trials

Q37. The process of calcification in atherosclerotic plaques is most similar to which biological process?

• Bone formation (ossification)
• Hematopoiesis
• Neurogenesis
• Apoptosis of erythrocytes

Correct Answer: Bone formation (ossification)

Q38. Which lipid parameter is most directly reduced by PCSK9 inhibitors?

• HDL cholesterol
• Triglycerides
• LDL cholesterol
• Lipoprotein(a)

Correct Answer: LDL cholesterol

Q39. Which process describes reverse cholesterol transport?

• Transfer of cholesterol from HDL to peripheral tissues
• Removal of cholesterol from peripheral macrophages to the liver via HDL
• Synthesis of cholesterol in the liver for VLDL secretion
• Hepatic uptake of triglyceride-rich lipoproteins

Correct Answer: Removal of cholesterol from peripheral macrophages to the liver via HDL

Q40. Which platelet-derived factor contributes to vascular smooth muscle migration and proliferation?

• Interleukin-1 receptor antagonist (IL-1Ra)
• Platelet-derived growth factor (PDGF)
• Adiponectin
• Fibrinogen degradation product D

Correct Answer: Platelet-derived growth factor (PDGF)

Q41. Which of the following best describes vulnerable plaque characteristics?

• Thick fibrous cap, small lipid core, few macrophages
• Thin fibrous cap, large lipid-rich necrotic core, abundant inflammatory cells
• Absent necrotic core and heavy calcification only
• Predominantly collagen-rich, non-inflammatory tissue

Correct Answer: Thin fibrous cap, large lipid-rich necrotic core, abundant inflammatory cells

Q42. What is the role of smooth muscle cell-derived collagen in plaque stability?

• Collagen weakens the fibrous cap and promotes rupture
• Collagen strengthens the fibrous cap and enhances stability
• Collagen stimulates LDL oxidation
• Collagen promotes intraplaque hemorrhage

Correct Answer: Collagen strengthens the fibrous cap and enhances stability

Q43. Which intracellular lipid transporter in macrophages facilitates cholesterol efflux to apoA-I/HDL?

• ABCA1 (ATP-binding cassette transporter A1)
• SR-A
• CD36
• NPC1L1

Correct Answer: ABCA1 (ATP-binding cassette transporter A1)

Q44. In patients with atherosclerosis, plaque neovascularization typically originates from:

• Vasa vasorum sprouting into the intima
• Direct transformation of smooth muscle cells into endothelial cells
• Migration of red blood cells into the lumen
• Bone marrow-derived osteoblasts

Correct Answer: Vasa vasorum sprouting into the intima

Q45. Which lifestyle factor most strongly accelerates endothelial dysfunction and atherosclerosis?

• Regular physical activity
• Cigarette smoking
• Moderate alcohol consumption
• High dietary fiber intake

Correct Answer: Cigarette smoking

Q46. The clinical benefit of lowering LDL cholesterol is primarily due to:

• Reduction in triglyceride synthesis
• Less LDL infiltration and reduced plaque lipid accumulation
• Increase in plaque neovascularization
• Promotion of smooth muscle cell apoptosis

Correct Answer: Less LDL infiltration and reduced plaque lipid accumulation

Q47. Which experimental biomarker is directly linked to plaque macrophage activation and may predict events?

• Myoglobin
• Soluble CD163 or imaging of macrophage activity with PET tracers
• Serum albumin levels
• Urinary sodium

Correct Answer: Soluble CD163 or imaging of macrophage activity with PET tracers

Q48. Which molecular change is most associated with increased endothelial permeability to lipoproteins?

• Upregulation of tight junction proteins like claudin-5
• Disruption of endothelial junctions and increased transcytosis
• Increased endothelial glycocalyx thickness
• Downregulation of caveolae-mediated transport

Correct Answer: Disruption of endothelial junctions and increased transcytosis

Q49. Which therapeutic approach targets inflammation directly in atherosclerosis management?

• PCSK9 inhibitors
• IL-1β neutralizing antibodies (e.g., canakinumab)
• HMG-CoA reductase activators
• Niacin supplements only

Correct Answer: IL-1β neutralizing antibodies (e.g., canakinumab)

Q50. Which statement best summarizes the multifactorial pathophysiology of atherosclerosis?

• Atherosclerosis is solely a lipid storage disease without inflammation
• Atherosclerosis is a dynamic interplay of lipids, endothelial dysfunction, inflammation, immune cells, and vascular remodeling
• Atherosclerosis results only from genetic factors and cannot be modified
• Atherosclerosis is entirely reversible without pharmacologic intervention

Correct Answer: Atherosclerosis is a dynamic interplay of lipids, endothelial dysfunction, inflammation, immune cells, and vascular remodeling

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