Hyperlipidemia is abnormally elevated levels of any or all lipids and/or lipoproteins in the blood. It is the most common form of dyslipidemia (which includes any abnormal lipid levels).
We know if you a thorough sclerosis is more than a passive deposition of fat in artery indeed complex interactions between vascular endothelial cells inflammatory leukocytes and cholesterol transporting liberal proteins as well as other cardiovascular risk factors lie at the root of atherosclerosis from boces causes the most dramatic clinical consequence of
Atherosclerosis acute coronary syndrome stroke and limb ischemia imbalance in plasma lipoproteins particularly a high ldl high levels of triglycerides rich lipoprotein such as v ldl and idl and low levels of hdl contribute importantly to atherosclerosis all cells require cholesterol and lipoproteins normally function to package this insoluble molecule in a
Form readily transported in the blood however factors such as an unhealthy diet or genetic predisposition overload this essential lipid transport pathway and contribute to the disability mia that promotes a thorough sporadic disease the body’s management of cholesterol begins in the liver i ldl levels can result from excessive production of triglyceride rich
Vldl as well as inadequate uptake of ldl by liver and peripheral cells due to low number of or genetic defects in ldl receptors statins by inhibiting cholesterol production in the liver can lower ldl levels improves the overall little protein profile and significantly reduce clinical cardiovascular events in several ways synthesis of cholesterol begins in
The cytosol when three molecules of acetyl coenzyme a interact to form hydroxymethyl louisville co a hmg-coa hmg-coa then reacts with hmg co-reductase an enzyme that resides in the membrane of the smooth endoplasmic reticulum the reductase is a tetrameric macro molecule the binding pocket for hmg-coa lies deep within each monomer with a neighboring monomer
Contributing a few additional binding interactions in total the tetramer has four pockets one within each monomer hmg-coa reductase using nadph catalyzes the reduction of hmg-coa to mevalonate after leaving the enzyme the vallon eight undergoes many subsequent transformations to form other sterile precursors and ultimately cholesterol statins competitively
Binds to the active site of hmg-coa reductase by blocking the binding of hmg-coa statins inhibit the conversion of h mg co a to mobility and therefore the pathway that leads to cholesterol let’s examine more closely the binding interaction between statins and hmg-coa reductase statins enter a narrow binding pocket and form 8 to 12 bonding interactions with
Hydrophobic moieties lining the pot the hmg co-reductase pocket undergoes a conformational change which envelops the bulky statins structure and further tightens the interaction here we can see the actual molecular detail of a satin binding to the active site statin therapy inhibits intracellular cholesterol synthesis causing cholesterol levels in the cell to
Fall cells must regulate cholesterol very closely changes in cholesterol levels triggers sensing mechanisms including a set of proteins bound to intracellular membranes called sterile regulatory element binding proteins or srebp in particular activation of srebp s by low cholesterol increases transcription of the ldl receptor gene the consequent rise in ldl
Receptor number promotes capture of ldl and vldl from the blood to maintain cellular cholesterol homeostasis srebp s also increased the synthesis of hmg-coa reductase itself in addition reduced cellular pools of cholesterol slow the rate of vldl production statin therapy can therefore lower blood vldl levels as a result levels of hdl may rise because of reduced
Transfer of cholesterol ester from hdl to vldl by the cholesterol ester transfer protein many studies suggest that the changes in blood lipoproteins particularly ldl lowering modulate inflammatory processes and thereby stabilized atherosclerosis reduced deposition of ldl interrupts the complex cascade of pathogenic events it starts with the oxidation of ldl and
Finally forms unstable thrombosis prone plaques increases in hdl they also stabilize the lesion by enhancing reverse cholesterol transport from the atherosclerosis lowering ldl also increases the availability of nitric oxide and endogenous vasodilator and an inhibitor of platelet aggregation and vascular inflammation lipid lowering can reduce levels of other
Inflammatory mediators including gamma interferon an inhibitor of collagen formation and also decreased levels of matrix metalloproteinases mmps that degrade arterial collagen these changes in college and metabolism thicken the plaques protective fibrous cap the strengthened cap resists rupture a frequent cause of thrombosis the possibility that additional non
Lipid or pleiotropic effects of statins contribute to their therapeutic benefit is an intriguing subject of investigation statins may influence cellular signaling for reduction of intracellular cholesterol precursors these precursors such as caramel geranyl pyrophosphate or gg pp and farnesyl pyrophosphate or fpp modulate activity of small g proteins for example
Reduced levels of gg pp can inhibit the g-protein rho resulting in greater expression of the enzyme nitric oxide synthase that produces nitric oxide by reducing levels of the procoagulant tissue factor decreasing pi-1 the inhibitor of tissue plasminogen activator and lowering platelet activation statins may also decrease thrombotic tendency lipid lowering may
Also limit endothelial production of superoxide anion and minimize oxidation of ldl to summarize the basic mechanisms described in this animation provide a foundation for us to understand how statins modify atherosclerosis thereby improving clinical outcomes in patients at risk for cardiovascular disease you
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Hyperlipidemia – Classification, Screening & Management : Pharmamates By Pharmamates