Atherosclerosis
Unregulated cholesterol production can lead to serious human disease. When the sum of cholesterol synthesized and cholesterol obtained in the diet exceeds the amount required for the synthesis of membranes, bile salts, and steroids, pathological accumulations of cholesterol in blood vessels (atherosclerotic plaques) can develop, resulting in obstruction of blood vessels (atherosclerosis). Atherosclerosis is linked to high levels of cholesterol in the blood, and particularly to high levels of LDL-bound cholesterol; there is a negative correlation between HDL levels and arterial disease. In familial hypercholesterolemia, a human genetic disorder, blood levels of cholesterol are extremely high and severe atherosclerosis develops in childhood. The metabolism of LDL and HDL intersects in the production and control of fatty streaks and potential plaques in blood vessels. Damage to the endothelium may be related to many factors, including normal turbulence of the blood, elevated LDL, especially modified or oxidized LDL, free radicals from cigarette smoking, homocystinemia, diabetes (glycation of LDL), and hypertension. The atherosclerotic lesion represents an inflammatory response sharing several characteristics with granuloma formation, and not simple deposition of cholesterol in the blood vessel.
Local inflammation recruits monocytes and macrophages with subsequent production of reactive oxygen species. LDL can become oxidized and then taken up, along with other inflammatory debris, by macrophages, which can become laden with cholesterol (foam cells). Initially the subendothelial accumulation of cholesterol-laden macrophages produces fatty streaks. As the fatty streak enlarges over time, necrotic tissue and free lipid accumulates, surrounded by epithelioid cells and eventually smooth muscle cells, an advanced plaque with a fibrous cap. The plaque eventually begins to occlude the blood vessel, causing ischemia and infarction in the heart, brain, or extremities. Eventually the fibrous cap may thin, and the plaque becomes unstable, leading to rupture and thrombosis. HDL may be protective by picking up accumulating cholesterol before the advanced lesion forms. Apo-l activates LCAT, which in turn adds a fatty acid to cholesterol to produce a cholesterol ester that dissolves in the core of the HDL. The HDL may subsequently be picked up by the liver through the apoE receptor or deliver cholesterol through the scavenger receptor SR-Bl (reverse cholesterol transport from the periphery to the liver). The HDL may also transfer the cholesterol to an IDL reforming a normal, unoxidized LDL particle.
Intext Questions
I. Choose the best answer
1. Lipid stored in the form of energy in the body adipose tissue is
(a) Steroid (b) Fatty acid
(c) Sphingolipid (d) Phospholipid
2. Combination of lipid and protein serving as the means of transporting lipids in the blood is
(a) Glycoprotein (b) Phosphoprotein
(c) Lipoprotein (d) None
3. The enzyme which catalyzes the formation of cholesteryl esters from lecithin and cholesterol.
(a) Lecithin-cholesterol acyl transferase
(b) D(b)-3-hydroxybutyrate dehydrogenase
(c) Lipoprotein lipase
(d) Carnitine palmitoyltransferase
4. A human genetic disorder in which the extremely high levels of blood cholesterol develops atherosclerosis is
(a) Familial hypercholesterolemia
(b) Obesity
(c) Apolipoproteinemia
(d) None
5. The molecule acting as both hydrophobic and hydrophilic is termed as
(a) Amphipathic (b) Aliphatic
(c) Polar (d) Nonpolar
II. Fill in the blanks
1. ……………….. act as electrical insulators, allowing rapid propagation
of depolarization waves along myelinated nerves.
2. Vegetable oil contains high amount of ……………….. triglycerides.
3. Aggregation of bile salts into ……………….. facilitates the absorption of lipids from the intestine.
4. A lipoprotein is a spherical molecule with water soluble ……………….. on the exterior.
5. Triglyceride is hydrolysed to ……………….. and ………………..
III. Match the following
1. Cholestrol (a) Phospholipid
2. Liposome (b) Diabetes mellitus
3. Linoleic (c) Steroid
4. Glycerophospholipid (d) Unsaturated fatty acid
5. Ketoacidosis (e) Amphipathic molecule
