Cholesterols are fundamental molecules for animals. Belonging to sterols class, these organic molecules take role on the composition of cell membranes, maintaining fluidity and integrity. Raised serum levels are highly associated with increased risk of stroke and heart disease. The World Health Organization points that one third of ischaemic heart disease can be attributed to high cholesterol (HC). The concern about treatment and prevention of HC and its consequences is global, once it is present in both developing and developed word as a risk factor for other health complications. This website explores a 2015 Medical Breakthrough regarding a new drug called PCSK9 inhibitors, which is assigned to be a good lowering-cholesterol medicament.

Basis of Transport of Cholesterol by The Blood Lipoprotein

Cholesterol is hydrophobic and must be transported through the bloodstream packaged as lipoproteins.  The major carriers of lipids are chylomicrons, VLDL (metabolism leads to IDL and LDL) and HDL. The apoproteins add to the hydrophilicity  and structural stability of the particle, activate enzymes for lipoprotein metabolism and act as ligands on the surface of lipoprotein that target specific receptors on peripheral tissues.

  • Chylomicrons: are synthesized from dietary lipids within the epithelial cells of small intestine and secreted in to the lymphatic vessels draining the gut. The apoprotein apoCII activates lipoprotein lipase (LPL), which hydrolyze the chilomicrons releasing the free fatty acids derived from core triacylglycerides into target cells.
Finally, the excess of LDL are available for nonspecific uptake by macrophages (scavenger cells) present near the endothelial cells of arteries.

Important: This exposure of vascular endothelial to high levels of LDL is related to induce the inflammatory process and initiate the formation of atherosclerosis.

  • High-Density Lipoprotein (HDL): HDL particles can be created by various mechanisms. The first is the synthesis by the liver and intestine whose shell, like that of other lipoproteins, lipids and apoproteins. The second is the budding of apoproteins from chylomicrons and VLDL and the third method for HDL generation is free apoAI, which adquires cholesterol and phospholipids from other lipoproteins and cell membranes. The benefit of HDL particles is the ability to remove cholesterol from cholesterol-laden cells and to return the cholesterol to the liver, making a reverse transport. Consequently, the likelihood that foam cells (macrophages that engulf LDL-cholesterol) will form within vessels wall is reduced. Reverse cholesterol transport is the directional movementVery-Low-Density Lipoprotein (VLDL): the excess of carbohydrate are converted to triacylglycerols which along with free and esterified cholesterol, phospholipids, and the major apoB-100 are packaged forming VLDL. These particles are secreted from the liver into bloodstream and accept apoproteins from high-density lipoprotein (HDL) particles. The apoproteins activate lipoprotein lipase which facilitates the hydrolysis of the triacylglicerol causing the release of fatty acids and glycerol. These fatty acids are oxidized as fuel by muscle cells, used in resynthesis or milk production in lactating breast. The VLDL remnants are take up from the blood by liver cells mediated by apoproteins.

  • Intermediate-Density Lipoprotein (IDL): approximately half of the VLDL remnants are not taken by the liver and form IDL. Then, the hepatic triglyceride lipase removes the additional triacylglycerols from IDL forming LDL.

  • Low-Density Lipoprotein (LDL): approximately 60% of the LDL is transported back to the liver to be endocytosed. The remaining 40% of LDL is carried to tissues such as adrenocortical and gonadal cells that also contain apoprotein receptors and they use the cholesterol for the synthesis of steroid hormones, membranes and vitamin D.  of cholesterol from the cell to the lipoprotein particle.  The HDL clearance is through its uptake by scavenger receptor SR-B1 or specific receptors on hepatocytes.