WBR0555

Author	[[PageAuthor::Ayokunle Olubaniyi, M.B,B.S [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::Cardiology
Prompt	[[Prompt::The "HDL hypothesis" suggests that high density lipoprotein-cholesterol (HDL-C) is inversely associated with atherosclerosis, and HDL-C has a protective role against cardiovascular disease. What is the main mechanism involved in the anti-atherogenic properties of HDL-C?]]
Answer A	AnswerA::Synthesis of prostacylin
Answer A Explanation	[[AnswerAExp::HDL may have a role in the increase of blood flow in patients with endothelial dysfunctions. This is carried out by its effect on vasodilation and prostacyclin synthesis. However, the anti-atherogenic properties of HDL-C are not derived from its association with prostacyclin synthesis.]]
Answer B	AnswerB::Caspase 3 activity
Answer B Explanation	AnswerBExp::Caspase 3 initiates apoptosis (programmed cell death) in cells. HDL, through its effect on caspase 3, prevents apoptosis in cells. It also reduces the generation of reactive oxygen species (ROS).
Answer C	AnswerC::Protein C and S activity
Answer C Explanation	AnswerCExp::HDL functions in preventing thrombus formation in the arteries through an effect on platelet activation and aggregation, which results in increased protein C&S activity, fibrinolysis, and endothelial tissue factor expression.
Answer D	AnswerD::Free cholesterol efflux from cells
Answer D Explanation	[[AnswerDExp::HDL cholesterol efflux uses the reverse cholesterol transport system (transport of cholesterol from the periphery to the liver), consisting of receptors such as ABCA1, scavenger receptors, and enzymes e.g., lecithin:cholesteryl acetyltransferase (LCAT) and cholesterylester transfer protein (CETP).]]
Answer E	AnswerE::Insulin secretion and sensitivity
Answer E Explanation	AnswerEExp::HDL increases insulin secretion through AMP-activated protein kinase in skeletal muscle, thus, mediating glucose metabolism especially among patients with type 2 diabetes.
Right Answer	RightAnswer::D
Explanation	[[Explanation::HDL is important anti-atherogenic lipoprotein that has been demonstrated to play a significant protective role against cardiovascular disease. Early studies have postulated that the quantity of HDL-C is inversely associated with atherosclerosis and have suggested that higher HDL-C concentrations are cardioprotective. More recent evidence, however, has failed to demonstrate a relationship between the quantity of HDL-C and atherosclerosis. Genetic and clinical studies have concluded that HDL-C efflux capacity, defined as the HDL-C ability to accept cholesterol from macrophages, is a more important factor in the the evaluation of the anti-atherogenic properties of HDL-C than HDL-C concentration alone. HDL cholesterol efflux uses the reverse cholesterol transport system (transport of cholesterol from the periphery to the liver), consisting of receptors such as ABCA1, scavenger receptors, and enzymes e.g., lecithin:cholesteryl acetyltransferase (LCAT) and cholesterylester transfer protein (CETP). The physiologic functions of HDL in an acute and chronic setting Educational Objective: HDL-C efflux capacity, defined as the HDL-C ability to accept cholesterol from macrophages, is a more important factor in the the evaluation of the anti-atherogenic properties of HDL-C than HDL-C concentration alone. References: Rohatgi A, Khera A, Berry JD, et al. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med. 2014;371:2383-93. Vergeer M, Holleboom AG, Kastelein JJP, et al. The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis? J Lipid Res. 2010; 51(8):2058-73.]]
Approved	Approved::Yes
Keyword	WBRKeyword::HDL, WBRKeyword::HDL physiology, WBRKeyword::HDL functions, WBRKeyword::Reverse cholesterol transport, WBRKeyword::Efflux capacity, WBRKeyword::HDL hypothesis
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