Screening models for cardiovascular drugs – antidyslipidemics MCQs With Answer

Screening models for cardiovascular drugs – antidyslipidemics covers in vitro, in silico and in vivo approaches used to discover and evaluate lipid‑lowering agents. B. Pharm students should understand HMG‑CoA reductase and CETP enzyme assays, LDL uptake in hepatic cell lines, high‑throughput docking, and animal models like Triton WR‑1339, poloxamer‑407, high‑fat diet, ApoE‑/‑ and LDLr‑/‑ mice. Key concepts include lipid profile biomarkers (TC, LDL‑C, HDL‑C, TG), IC50/EC50 determination, ADME/Tox screening, plaque analysis (Oil Red O), and safety monitoring (ALT, AST, CK). This knowledge links pharmacology, formulation and preclinical testing for effective antidyslipidemic development.

Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which in vitro assay directly measures inhibition of the rate-limiting enzyme in cholesterol biosynthesis?

• LDL uptake assay in HepG2 cells
• HMG‑CoA reductase enzyme assay
• CETP activity assay
• Bile acid binding assay

Correct Answer: HMG‑CoA reductase enzyme assay

Q2. Triton WR‑1339 is used in animal studies primarily to:

• Induce hepatic steatosis through fat feeding
• Cause acute hyperlipidemia by blocking lipoprotein lipase
• Promote atherosclerotic plaque regression
• Enhance cholesterol absorption from intestine

Correct Answer: Cause acute hyperlipidemia by blocking lipoprotein lipase

Q3. Which genetically modified mouse is most commonly used to study atherosclerosis and efficacy of antidyslipidemic drugs?

• SCRN1 knockout mouse
• ApoE‑/‑ mouse
• CFTR‑/‑ mouse
• P53 transgenic mouse

Correct Answer: ApoE‑/‑ mouse

Q4. Oil Red O staining in preclinical studies is used to visualize:

• Collagen deposition in myocardium
• Neutral lipid accumulation in tissues and plaques
• Apoptotic nuclei in atherosclerotic lesions
• Reactive oxygen species in vascular cells

Correct Answer: Neutral lipid accumulation in tissues and plaques

Q5. A primary in vitro screen to find small molecules that increase LDL receptor expression would most likely use:

• Cardiomyocyte contractility assay
• Hepatic cell line (HepG2) LDL uptake assay
• Differential scanning calorimetry
• Vascular ring contraction assay

Correct Answer: Hepatic cell line (HepG2) LDL uptake assay

Q6. Which measurement is the most direct pharmacodynamic endpoint for an antidyslipidemic in animal screening?

• Plasma ALT levels
• Plasma LDL‑C concentration
• Renal clearance rate
• Heart rate variability

Correct Answer: Plasma LDL‑C concentration

Q7. Poloxamer‑407 model induces hyperlipidemia by:

• Inhibiting bile acid reabsorption
• Blocking lipoprotein lipase and increasing VLDL
• Activating HMG‑CoA reductase
• Enhancing intestinal cholesterol absorption

Correct Answer: Blocking lipoprotein lipase and increasing VLDL

Q8. In early screening, an IC50 value represents:

• Concentration causing 50% cell death
• Concentration of drug at 50% plasma protein binding
• Concentration producing 50% inhibition of target activity
• Time to reach 50% of maximum effect

Correct Answer: Concentration producing 50% inhibition of target activity

Q9. A common positive control (reference drug) in statin screening studies is:

• Atorvastatin
• Metformin
• Loperamide
• Warfarin

Correct Answer: Atorvastatin

Q10. CETP inhibitors are screened to achieve which effect on lipoproteins?

• Decrease HDL cholesterol
• Increase HDL cholesterol and modify LDL levels
• Increase triglyceride synthesis
• Block intestinal cholesterol uptake

Correct Answer: Increase HDL cholesterol and modify LDL levels

Q11. Which in silico technique helps prioritize compounds before wet‑lab screening for antidyslipidemics?

• Molecular docking to HMG‑CoA reductase
• Patch clamp electrophysiology simulations
• In vivo metabolic cage modeling
• Clinical trial simulation of endpoints

Correct Answer: Molecular docking to HMG‑CoA reductase

Q12. DiI‑labeled LDL uptake assay detects:

• Neutral lipid content by colorimetric change
• Cellular uptake of fluorescent LDL particles
• Blood pressure changes in animals
• Hepatocyte bile acid secretion

Correct Answer: Cellular uptake of fluorescent LDL particles

Q13. Which biomarker is most indicative of muscle toxicity during statin screening?

• Plasma creatine kinase (CK)
• Serum creatinine
• Plasma HDL‑C
• Blood glucose

Correct Answer: Plasma creatine kinase (CK)

Q14. In an atherosclerosis study, the en face aortic oil red O assay quantifies:

• Lesion lipid area as percentage of aortic surface
• Endothelial nitric oxide synthase expression
• Arterial stiffness by tension testing
• Plaque collagen content

Correct Answer: Lesion lipid area as percentage of aortic surface

Q15. Which animal model is particularly useful for studying dietary cholesterol effects and large plaque formation?

• Zebrafish larvae
• Watanabe heritable hyperlipidemic (WHHL) rabbit
• C. elegans
• Guinea pig pulmonary model

Correct Answer: Watanabe heritable hyperlipidemic (WHHL) rabbit

Q16. For ADME profiling in early screening, which assay assesses metabolic stability?

• Human liver microsome stability assay
• LDL oxidation assay
• Oil Red O staining
• HMG‑CoA reductase inhibition test

Correct Answer: Human liver microsome stability assay

Q17. Which endpoint helps assess anti‑inflammatory effects of antidyslipidemic candidates in plaques?

• Macrophage content by immunostaining (CD68)
• Serum sodium concentration
• Urine protein level
• ECG QT interval

Correct Answer: Macrophage content by immunostaining (CD68)

Q18. A high‑throughput screening (HTS) campaign for new lipid‑lowering agents should prioritize assays that are:

• Low throughput and qualitative
• Robust, miniaturizable, and quantitative
• Expensive and time‑consuming per well
• Exclusively animal‑based

Correct Answer: Robust, miniaturizable, and quantitative

Q19. Which compound is used experimentally to inhibit cholesterol absorption at the intestinal brush border and can be used as a comparator?

• Gemfibrozil
• Ezetimibe
• Niacin
• Digoxin

Correct Answer: Ezetimibe

Q20. Foam cell formation assays in macrophages primarily measure:

• Accumulation of cholesteryl esters and lipid droplets in macrophages
• Endothelial barrier integrity
• Platelet aggregation tendency
• Hepatocyte bile synthesis

Correct Answer: Accumulation of cholesteryl esters and lipid droplets in macrophages

Q21. Which preclinical assay would best identify compounds that upregulate reverse cholesterol transport?

• ABCA1 expression assay and cholesterol efflux to apoA‑I
• Renal clearance measurement
• Vascular reactivity to phenylephrine
• HMG‑CoA reductase enzymatic assay

Correct Answer: ABCA1 expression assay and cholesterol efflux to apoA‑I

Q22. In selecting doses for rodent antidyslipidemic studies, which principle is most important?

• Use only a single very high dose to ensure effect
• Use pharmacokinetically informed doses including subtherapeutic to high ranges
• Match human tablet strength exactly by mg/kg
• Choose doses based solely on cost

Correct Answer: Use pharmacokinetically informed doses including subtherapeutic to high ranges

Q23. Which safety parameter is routinely monitored for hepatotoxicity during statin screening?

• ALT and AST levels
• Blood hemoglobin
• Serum amylase
• Urinary ketones

Correct Answer: ALT and AST levels

Q24. Zebrafish larvae are increasingly used in lipid screening because they offer:

• Large size and long lifespan like rabbits
• Transparent embryos, genetic tractability, and rapid readouts of lipid deposition
• Exact human lipoprotein profiles
• Complete absence of cholesterol metabolism

Correct Answer: Transparent embryos, genetic tractability, and rapid readouts of lipid deposition

Q25. Which analytical technique is essential for quantifying plasma drug concentration in PK studies of candidate antidyslipidemics?

• LC‑MS/MS
• Light microscopy
• Gel electrophoresis
• Polarimetry

Correct Answer: LC‑MS/MS

Q26. Measuring triglycerides, total cholesterol and HDL in plasma provides which useful parameter after calculation?

• Estimated LDL‑C by Friedewald equation
• Direct aortic plaque volume
• Liver microsomal clearance
• Renal filtration fraction

Correct Answer: Estimated LDL‑C by Friedewald equation

Q27. Which cell viability assay is commonly paired with in vitro lipid assays to rule out cytotoxicity?

• MTT or resazurin reduction assay
• Oil Red O staining
• ELISA for LDL
• Western blot for HMG‑CoA

Correct Answer: MTT or resazurin reduction assay

Q28. PCSK9 inhibitors reduce LDL‑C primarily by:

• Increasing intestinal cholesterol absorption
• Blocking LDL receptor degradation and increasing receptor recycling
• Inhibiting HMG‑CoA reductase directly
• Sequestering bile acids in intestine

Correct Answer: Blocking LDL receptor degradation and increasing receptor recycling

Q29. When interpreting preclinical lipid data, which factor can confound results if not controlled?

• Animal diet composition and housing conditions
• Brand of pipette tips used
• Color of animal cage bedding only
• Operator handedness

Correct Answer: Animal diet composition and housing conditions

Q30. Which combined screening strategy offers the best path from hit discovery to lead selection for antidyslipidemics?

• Only in vivo tests with no prior in silico or in vitro filters
• In silico docking → in vitro enzyme/cell assays → ADME/Tox profiling → in vivo efficacy and safety models
• Direct human trials without preclinical work
• Random compound testing in clinical settings

Correct Answer: In silico docking → in vitro enzyme/cell assays → ADME/Tox profiling → in vivo efficacy and safety models

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com