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Over the last few decades most countries in the world have experienced great transition in social structures, economic, politics, education and environment. This has resulted in shift from agricultural and rural societies to industrial and urban societies. South Asian region is also undergoing rapid urbanization, industrialization and major technological and life style changes, which has greatly affected the prevalence of cardiovascular diseases. Although the absence of well-established disease surveillance mechanism prevent precise estimation of the rate of prevalence of cardiovascular disease, the direction of change is clear the rate of prevalence is rising. More accurate estimation of disease burden, risk factors and time trends would helps to form better policies and guidelines for prevention and treatment.
Thus South Asian region is facing a period of challenge and opportunity as it embarks on the efforts to control the emerging epidemic of cardiovascular disease. National and regional efforts must be coordinated to recognize this epidemic and respond without delay.
WHAT ARE LIPOPROTEINS
Triglycerides and cholesterol are transported in the blood as Lipoproteins. Lipoproteins are named according to their density which depends on the percent of proteins in the particle. The higher the percent of protein, the higher the density.
From the least dense to most dense:
Chylomicrons<VLDL<IDL<LDL<HDL
Structure and Composition of Lipoproteins:
All Lipoproteins consist of a hydrophilic shell and a hydrophobic core. The hydrophilic shell contains proteins, phospholipids and unestrified cholesterol. The hydrophobic core contains the neutral lipids, triacylglycerols and cholesterol esters which are highly insoluble in water.
Classes of Lipoproteins:
The four major classes of lipoproteins in human serum can be separated by electrophoresis on the bases of their size and charge or by centrifugation on the basis of their density.
Chylomicrons:
Chylomicrons are the least dense of the lipoproteins and do not migrate in an electric field. They are formed in intestinal mucosa, and transport dietary triacylglycerol(TAG) and Cholesterol ester(CE) Chilomicrons are synthesized in endoplasmic reticulum of intestinal epithelial cells. The TAGs in chylomicrons are hydrolyzed by Lipoprotein lipase, an enzyme attached to the luminal surface of the vasculature of cardiac muscles, skeletal muscles and adipose tissues. Chilomicrons contain several apoprotins, including apo B48, Apo E and Apo C-11. Apo B48 is unique to chylomicrons, Apo C-11 activates lipoprotein lipase resulting in fatty acid release to heart, skeletal muscles and mammary glands. The presense of apo E facilitates the clearance of chylomicron remnants by the liver.
2: Very Low Density Lipoproteins:(VLDL)
VLDL are synthesized in the liver and transport TAG and CE. VLDLs are composed mainly of TAG, yet are more enriched in CE than are chylomicrons. VLDLs contain apo B100(required for uptake of LDL in peripheral tissues) Apo E (mediates uptake of remnants by the liver) and Apo c11 (activates lipoprotein lipase in capillary endothelium).When VLDL arrives in adipose capillaries, Apo C11 activates lipoprotein lipase. This releases fatty acids which are taken into the adipose and re-esterified into triglycerides. The glycerol returns to the liver. After VLDL release trigycerides, they become IDL. Intermediate density lipoproteins.
3:Intermediate Density Lipoproteins:IDL
IDLs also called (VLDL remnants) may be scavenged by the liver (Apo E) or may pick up cholesterol from HDL. As they acquire cholesterol they become LDL. The transfer of cholesterol ester from HDL to IDL is mediated by cholesterol ester transfer protein(CEPT)
4:Low Density Lipoproteins:LDL
LDL is generated from VLDLs and IDLs by the action of lipoproteins lipase, thus increasing the relative proportion of cholesterol esters in the neutral core. The major function of LDL is to transport cholesterol to the extra hepatic tissues where it is taken up by the receptor-mediated endocytosis. The LDL particle retains only Apo B100 and the uptake of LDL by cells is initiated by the interaction of Apo B100 with LDL receptors on the plasma membranes.
High Density Lipoproteins:(HDLS)
HDLs are synthesized by the liver and are approximately 50% protein. When the particle is secreted by the Liver, the core region is relatively empty. HDLs perform two major functions:
A: Circulating reservoir for apoproteins:
Members of the apo A, Apo C and Apo E families can be transferred back and forth between other lipoproteins. Newly synthesized chylomicrons and VLDL particles obtain some of their apoproteins from the HDL reservoir following secretion.
b: Reverse Cholesterol Transport:
HDLs are important in moving cholesterol from extra hepatic tissues to the liver. Elevated plasma levels of HDL are associated with decreased incidence of coronary atherosclerosis. Cholesterol is taken up from the surface of cells by HDL, esterified to cholesterol esters and ultimately returned to liver either by uptake of HDL particles by the liver or by the transfer of cholesterol esters to the VLDL and chylomicron remnants followed by remnant uptake. Two proteins play important roles in reverse cholesterol transport.
1_ Lecithin cholesterol acyl transferase(LCAT)
LCAT is a plasma enzyme that esterifies HDL cholesterol. The fatty acid used for esterfication comes from lecithin (Phosphatidylcholine). LCAT is activated by apo A-1 which is associated with HDL.
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