week 9c- reverse cholesterol transport

reverse cholesterol transport

excess cholesterol from a tissue attaches to HDL to be transported in the liver and excreted through fecal loss, feedback cholesterol transport to liver for excretion

diverse functions of HDL

cholesterol efflux, vaso-protective, endothelial function, NO production, reverse cholesterol transport, anti-inflammatory, anti-oxidant, anti-thrombotic

heterogeneity of HDL

discoidal or spherical, larger/less dense or smaller/more dense

what does reverse cholesterol start with?

a discoidal, nascent HDL particle (basically an apoA1), doesn't have much lips cargo, job is to pick up excess cholesterol from peripheral tissues

reverse cholesterol transport- step 1

begins with production of Apo-A1 which is synthesized and secreted from the liver into the blood compartment to create discoidal nascent HDL

reverse cholesterol transport- step 2

ABCA1 (efflux transporter) moves excess cholesterol to HDL3, ApoA stimulated LCAT which is important for growth and uptake of HDL in blood

reverse cholesterol transport- step 3

develops from HDL3 to HDL2 by gaining more cholesterol, full bus which is then transported back to the liver through SR-B1 which uptakes cholesterol from HDL and then allows HDL2 regeneration

LCAT

esterfies and traps cholesterol in HDL, significant role in formation of mature HDL (requires apoA1), without it HDL can’t grow or pickup excess cholesterol

HDL in reverse cholesterol transport

as a repository for apoC and apoE in the plasma, as a mediator of RCT

CETP

mediates an indirect RCT route, cholesterol is transferred from HDL to VLDL and LDL, secreted by liver/adipose tissue, promotes transfer of CE from HDL to VLDL in exchange for TG

following CETP transfer, HDL (now TG-enriched) becomes

a substrate for hepatic lipase which will help HDL to offload this TG to create more space on the ‘bus’

hepatic lipase (HL)

synthesized in and secreted from the liver, inactive enzyme attached to cell surface, HDL regulates displacement and activity of HL, circulating HL facilitates clearance of TG from VLDL and also from HDL

following CETP activity, how would the lipid composition of VLDL/LDL and HDL change?

the HDL particle would have more triglycerides and the VLDL/LDL will have more cholesterol

how would the transfer between VLDL/LDL and HDL affect CVD risk in a BAD way?

you would have higher VLDL/LDL cholesterol which will go through lipoprotein and hepatic lipase which will lead to small, dense, LDL particles leading to arterial deposition

how would the transfer between VLDL/LDL and HDL affect CVD risk in a GOOD way?

you would have lower HDL cholesterol, which will go through hepatic lipase leading to small, dense, HDL-particle (HDL-regeneration), leading to more reverse cholesterol transport