A cross-section of the right coronary artery of a 34-year-old Caucasian male who died in the cardiac intensive care unit is shown on the slide below. His father died of a heart attack at the age of 40. Assuming this patient's disease had a genetic basis, poor receptor expression in which of the following organs is most likely responsible for his condition?

Question

A cross-section of the right coronary artery of a 34-year-old Caucasian male who died in the cardiac intensive care unit is shown on the slide below.  His father died of a heart attack at the age of 40.  Assuming this patient's disease had a genetic basis, poor receptor expression in which of the following organs is most likely responsible for his condition?

Quizplus · Accepted Answer

This patient's right coronary artery (RCA) shows significant occlusion by a large atheromatous plaque with a soft, yellow, lipid core composed mainly of cholesterol and cholesterol esters. Presumably, this patient died from a complication of advanced atherosclerosis, such as a myocardial infarction. His father's similar fate at a young age suggests a familial condition, most likely familial hypercholesterolemia. Familial hypercholesterolemia is one of the most common inherited disorders, and results from autosomal dominant mutations of the LDL receptor gene. The liver LDL receptor is normally the greatest contributor to the removal of cholesterol-containing IDL and LDL particles from the circulation. Although numerous other cell types, including smooth muscle cells, adrenocortical cells, fibroblasts, and lymphocytes also express high-affinity LDL receptors, approximately 70% of the plasma LDL is normally cleared by the liver. Heterozygotes with one mutant LDL receptor gene have a 2- to 3-fold elevation of plasma cholesterol from birth, due to reduced hepatic IDL and LDL uptake. Homozygotes may have a 5- to 6-fold elevation. In both heterozygotes and homozygotes, the progression of atherosclerosis with aging is accelerated. Complications include coronary artery disease at an unusually young age, as was the case for the patient in the vignette. (Choices A, B, D, E and F) Although many cell types express the LDL receptor, their rate of LDL uptake from the circulation is usually less than that of hepatocytes. The liver is also the major site of cholesterol catabolism and excretion, making it the most important organ in serum cholesterol level homeostasis. Educational Objective: Familial hypercholesterolemia, one of the most common autosomal dominant disorders, is the result of heterozygous or homozygous LDL receptor gene mutations, which cause hepatocyte under-expression of functional LDL receptors. This condition can lead to accelerated atherosclerosis and early-onset coronary artery disease.

A Cross-Section of the Right Coronary Artery of a 34-Year-Old