For some time scientists have believed that cholesterol plays a major role in heart disease because people with familial hypercholesterolemia, a genetic defect, have six to eight times the normal level of cholesterol in their blood and they invariably develop heart disease. These people lack cell-surface receptors for low-density lipoproteins (LDL’s), which are the fundamental carriers of blood cholesterol to the body cells that use cholesterol. Without an adequate number of cell-surface receptors to remove LDL’s from the blood, the cholesterol-carrying LDL’s remain in the blood, increasing blood cholesterol levels. Scientists also noticed that people with familial hypercholesterolemia appear to produce more LDL’s than normal individuals. How, scientists wondered, could a genetic mutation that causes a slowdown in the removal of LDL’s from the blood also result in an increase in the synthesis of this cholesterol-carrying protein?
Since scientists could not experiment on human body tissue, their knowledge of familial hypercholesterolemia was severely limited. However, a breakthrough came in the laboratories of Yoshio Watanabe of Kobe University in Japan in 1980. Watanabe noticed that a male rabbit in his colony had ten times the normal concentration of cholesterol in its blood. By appropriate breeding, Watanabe obtained a strain of rabbits that had very high cholesterol levels. These rabbits spontaneously developed heart disease. To his surprise, Watanabe further found that the rabbits, like humans with familial hypercholesterolemia, lacked LDL receptors. Thus, scientists could study these Watanabe rabbits to gain a better understanding of familial hypercholesterolemia in humans.
Prior to the breakthrough at Kobe University, it was known that LDL’s are secreted from the liver in the form of a precursor, called very low-density lipoproteins (VLDL’s), which carry triglycerides as well as relatively small amounts of cholesterol. The triglycerides are removed from the VLDL’s by fatty and other tissues. What remains is a remnant particle that must be removed from the blood. What scientists learned by studying the Watanabe rabbits is that the removal of the VLDL remnant requires the LDL receptor. Normally, the majority of the VLDL remnants go to the liver where they bind to LDL receptors and are degraded. In the Watanabe rabbit, due to a lack of LDL receptors on liver cells, the VLDL remnants remain in the blood and are eventually converted to LDL’s. The LDL receptors thus have a dual effect in controlling LDL levels. They are necessary to prevent oversynthesis of LDL’s from VLDL remnants and they are necessary for the normal removal of LDL’s from the blood. With this knowledge, scientists are now well on the way toward developing drugs that dramatically lower cholesterol levels in people afflicted with certain forms of familial hypercholesterolemia.
17. In the passage, the author is primarily concerned with
(A) presenting a hypothesis and describing compelling evidence in support of it
(B) raising a question and describing an important discovery that led to an answer
(C) showing that a certain genetically caused disease can be treated effectively with drugs
(D) explaining what causes the genetic mutation that leads to heart disease
(E) discussing the importance of research on animals for the study of human disease18. Which of the following drugs, if developed, would most likely be an example of the kind of drug mentioned in line
(A) A drug that stimulates the production of VLDL remnants
(B) A drug that stimulates the production of LDL receptors on the liver
(C) A drug that stimulates the production of an enzyme needed for cholesterol production
(D) A drug that suppresses the production of body cells that use cholesterol
(E) A drug that prevents triglycerides from attaching to VLDL’s
19. The passage supplies information to answer which of the following questions?
(A) Which body cells are the primary users of cholesterol?
(B) How did scientists discover that LDL’s are secreted from the liver in the form of a precursor?
(C) Where in the body are VLDL remnants degraded?
(D) Which body tissues produce triglycerides?
(E) What techniques are used to determine the presence or absence of cell-surface receptors?
20. According to the passage, by studying the Watanabe rabbits scientists learned that
(A) VLDL remnants are removed from the blood by LDL receptors in the liver
(B) LDL’s are secreted from the liver in the form of precursors called VLDL’s
(C) VLDL remnant particles contain small amounts of cholesterol
(D) triglycerides are removed from VLDL’s by fatty tissues
(E) LDL receptors remove LDL’s from the blood
21. The development of drug treatments for some forms of familial hypercholesterolemia is regarded by the author as
(A) possible, but not very important
(B) interesting, but too costly to be practical
(C) promising, but many years off
(D) extremely unlikely
(E) highly probable
22. The passage implies that if the Watanabe rabbits had had as many LDL receptors on their livers as do normal rabbits, the Watanabe rabbits would have been
(A) less likely than normal rabbits to develop heart disease
(B) less likely than normal rabbits to develop high concentrations of cholesterol in their blood
(C) less useful than they actually were to scientists in the study of familial hypercholesterolemia in humans
(D) unable to secrete VLDL’s from their livers
(E) immune to drugs that lower cholesterol levels in people with certain forms of familial hypercholesterolemia
23. The passage implies that Watanabe rabbits differ from normal rabbits in which of the following ways?
(A) Watanabe rabbits have more LDL receptors than do normal rabbits.
(B) The blood of Watanabe rabbits contains more VLDL remnants than does the blood of normal rabbits.
(C) Watanabe rabbits have fewer fatty tissues than do normal rabbits.
(D) Watanabe rabbits secrete lower levels of VLDL’s than do normal rabbits.
(E) The blood of Watanabe rabbits contains fewer LDL’s than does the blood of normal rabbits.